2021 SUP Research Symposium Participants

Presentation Time: 9:00-9:20

Home University: UNC-Chapel Hill

Research Mentor: Kennita Johnson, Biomedical engineering

Program: SMART

Research Title: Towards Early Detection of Diabetic Kidney Disease Using Contrast Enhanced Ultrasound Perfusion Parameters

Diabetes is the leading cause of kidney disease and 40% of type 2 diabetic patients will go on to develop end stage kidney disease. However, current clinical markers lag behind disease progression. In contrast to blood and urine markers, renal perfusion may help to detect diabetic kidney disease quicker. Earlier detection will allow clinicians to identify patients susceptible to developing kidney disease and take steps to mitigate and possibly prevent disease progression. Compared to other imaging modalities, ultrasound is cost effective, portable, widely accessible, does not involve ionizing radiation, and ultrasound contrast agents (microbubbles) are safe for use in compromised kidneys. Microbubbles are highly echogenic micron-sized gas particles surrounded by a lipid shell that enable detection of microvascular flow. Microbubble transit through the kidney was observed to capture the wash in and wash out phases, in order to assess changes in renal perfusion between healthy, insulin-resistant, and diabetic populations. Time-intensity curve data from the bolus injection was fit with three different perfusion models (log-normal, lagged normal, and gamma variate) to determine the best fit model for each data set. Perfusion parameters such as mean transit time (MTT), time to peak enhancement (TTP), and area under the curve were extracted to identify parameters with the potential to distinguish healthy and diseased kidneys.

Presentation Time: 9:00-9:20

Home University: UNC-Chapel Hill

Research Mentor: Dorothy Erie, Chemistry

Program: CSS

Research Title: DNA Mismatch Repair Proteins

DNA mismatch repair is essential for maintenance of genome stability. Mismatch repair (MMR) corrects errors made during DNA replication, including mismatches and insertion-deletion loops. This process enhances DNA replication by about 100 to 1000-fold by improving the accuracy of the incorporated base pairs. We used the MMR protein MutS from Thermus aquaticus as our model. Previous studies have shown that a glutamate in the DNA binding domain of MutS hydrogen bonds with a mismatched nucleotide leading to a change of shape in the DNA, determinant of repair. In this study, we were specifically interested in MutS’s interaction with thymine inserts (T-bulges) and GT mismatches. Previous studies have shown that wild type MutS can repair T-bulges and GT mismatches whereas mutating glutamate to alanine, MutS can only repair T-bulges and not GT mismatches. We have mutated the glutamate to alanine to inhibit MutS causing conformational changes in the DNA with GT mismatches leading to MMR so we could study how MutS is interacting with the DNA. To visualize the protein-DNA interaction, a Cys mutation was also introduced into the MutS protein so it could be fluorescently labeled. Single molecule fluorescence resonance energy transfer (smFRET) experiments were performed to visualize measure conformational changes of the mutated protein and DNA. FRET is a function of the distance between the donor and acceptor fluorescent dyes.

Presentation Time: 9:00-9:20

Home University: UNC-Chapel Hill

Research Mentor: Michael Falvo, Physics

Program: McNair

Research Title: Development of a Phagocytic Uptake Assay based on Actin Regulator Manipulation

Phagocytosis is an essential part of the immune system in which phagocytes engulf foreign bodies. Engulfment relies on force-dependent reorganization of a cell’s cytoskeleton which is primarily made up of actin. Actin undergoes a complicated orchestration whereby polymerizing and restructuring during uptake. There are many key contributors over the course of engulfment that play specific roles in actin polymerization. An assay was developed to influence polymerization in RAW Ftracin_Halo Macrophages. The phagocytes were supplied with 6um IgG-coated polystyrene beads and treated with 100nM Liposaccharide and 100nM Latrunculin A (LatA). Uptake ratio was defined as the number of active cells to the number of total cells. We hypothesized that LPS would increase uptake and Latrunculin A (LatA) would decrease uptake. The Fisher Exact Test along with comparative plots are presented to display variances. This assay can be built upon for force scaling experiments using Atomic Force Microscopy (AFM). AFM measurements can quantify forces through the stages of phagocytosis and the experimental design can benefit from the controls of this study. Understanding how actin regulators affect uptake gives insight into the different signaling pathways associated with phagocytosis. Disease states with respect to the immune system can be addressed with biomedical applications that affect cell engulfment.

Presentation Time: 9:00-9:20

Home University: North Carolina Central University

Research Mentor: Kristina De Paris, Microbiology and Immunology

Program: M&I-HBCU SROP

Research Title: Adjuvant Induced Gene Expression Rhesus Macaques

To reduce infant HIV infection rates by vaccination, the current study was designed to identify innate molecular signatures activated by two different vaccine regimens. Previously, we determined that infant rhesus macaques (RMs) vaccinated with an HIV envelope (Env) protein with a toll-like receptor (TLR) 7/8 adjuvant versus alum adjuvant had higher Env-specific antibody responses. Here, we selected two adjuvants, TLR7/8-based R848 or TLR3-based Ampligen, in an HIV vaccine regimen consisting of Modified Vaccinia Ankara (MVA) expressing HIV Env and HIV env protein.

Infant RMs were divided into four groups. Control RMs (Group A) received empty MVA intradermally (ID) and sublingually (SL) at weeks (wks) 0 and 4, and Ampligen or R848 only at wks 4 and 10, respectively. Group B and C RMs were immunized with MVA-Env (wks 0, 4) and HIV Env protein (wks 4, 10) in Ampligen or R848, respectively. One day after each immunization, 0.25mL of EDTA-anticoagulated blood was collected. Samples were stored in TRIzol until RNA extraction. Purified RNA was analyzed using the nCounter Nonhuman Primate Immunology Panel by NanoString to assess changes in gene expression. The data will be analyzed using the nCounter Analysis Software to identify specific biological pathways induced by the two distinct adjuvant. We will then correlate the different innate response to the vaccine-induced antibody responses to determine the optimal vaccine regimen.

Presentation Time: 9:00-9:20

Home University: Bennett College

Research Mentor: Ann Sam, Jessica Steinbrenner, Frank Porter Graham Child Development Institute

Program: McKinney Scholars Program

Research Title: Self determination in early Childhood

Abstract
During this presentation, I will share information on self-determination in early childhood. Self-determination is a way that provides support to individuals so they can have the ability to learn, grow, and much more. There are several aspects of becoming self-determined: choice-making, decision-making, goal setting, problem-solving, planning, self-management, and self-advocacy. Throughout my presentation, I will be speaking about the self-determination Learning Model of Support (SDLMS). The self-determination learning model of support guides children towards independence by helping them set a goal, take action, and adjusting to that specific goal. In addition, I will be providing a case study example from my life. It will illustrate what self-determination can look like to help children with or without a disability. I will share an interview with my parents that I conducted. In this interview, they spoke about everything I experienced in the early stages of my life related to self-determination, from my challenges to my success.
In conclusion, self-determination can be essential for children with or without a disability. Self-determination skills enable individuals to assume greater responsibility and control. Moreover, when people with disabilities take responsibility for planning and decision-making, others change their views and expectations. The reason why I choose this project was that I could make a connection.

Presentation Time: 9:25-9:45

Home University: UNC-Chapel Hill

Research Mentor: Kristen Lindquist, Psychology and Neuroscience

Program: SMART

Research Title: Amygdala activation during negative emotional experiences

Salience detection facilitates scanning and learning from environments, enabling organisms to focus on relevant stimuli in their visual field for the purpose of survival. Although the brain circuits that underlie this process center around the amygdala, the psychological mechanisms that facilitate such process are poorly understood. Ambiguity has been shown to drive salience detection, and the amygdala has been shown to activate during various emotional experiences, including fear and sadness. Here, we merge these previous findings by testing whether psychological features (appraisals, including ambiguity of a situation) characterize amygdala activity related to instances of fear and sadness. Using evocative stimuli, fear and sadness were induced in forty-five participants while undergoing fMRI; half the participants were White Americans, while the other half were Chinese Natives. A separate and independent American sample rated the stimuli on ten features, or appraisals (e.g., dangerousness of the situation, ambiguity of the situation). Through hierarchical linear regression, we find that ambiguity has a robust effect on bilateral amygdala activation related to experiences of fear and sadness above and beyond the other appraisals. Moreover, we find this effect holds across both Chinese and American participants, suggesting ambiguity during instances of fear and sadness may recruit amygdala activation similarly across the cultural groups. Overall, our results suggest ambiguity in negative emotional experiences renders them salient to the human mind.

Presentation Time: 9:25-9:45

Home University: Fayetteville State University

Research Mentor: Christina Kasprzak and Thomas McGhee, Technical Assistance

Program: McKinney Scholars Program

Research Title: How can we Educate, Empower and Connect Families about their Rights within the Individualized Education Plan ( IEP)

My research project is focused on finding ways to educate, empower and connect families about knowing their rights within the IEP process. I had the opportunity to interview five individuals within the education arena: a teacher, administrator, provider, parent, and lastly, a student. I interviewed them to see the different issues they are facing and how we can improve communication within the IEP process. There was one common thread throughout all my interviews: the process and their rights are not explained with a clear understanding. Throughout my presentation, I will provide recommendations that will help improve the issues so that we can start closing the gap of families not understanding the rights.

Presentation Time: 9:25-9:45

Home University: UNC-Chapel Hill

Research Mentor: Dr. Leon Coleman, Pharmacology

Program: CSF, CSS

Research Title: Persistent Effects of Alcohol Use on Alzheimer's Disease Tau Pathology

Several epidemiological studies have found that heavy alcohol use may increase the risk of developing Alzheimer’s disease (AD), although the mechanisms behind this link are unclear. The increase in neuroinflammation seen during alcohol abuse and AD may drive this connection, however, the effects of heavy alcohol use on Alzheimer’s pathology during abstinence have not been explored. Additionally, the persistent effects of alcohol abuse on the sexual dimorphism of AD pathology remain to be explored. Triple transgenic AD mice models were treated with ethanol for three months during adulthood followed by five months of abstinence to model sustained recovery following heavy alcohol use until Alzheimer’s pathology begins to develop. By visualizing brain tissue via immunohistochemistry and analyzing cortical and hippocampal protein and gene expression through western blotting and RT-PCR, the sustained changes in AD pathology as a result of alcohol abuse were studied. The two pathological hallmarks of Alzheimer’s disease (amyloid plaques and tau tangles) were measured to directly analyze these conditions. Although there was not a persistent increase in amyloid plaques as a result of alcohol use, there was a persistent increase in phosphorylated tau in female subjects, particularly in the piriform cortex, which is known to be sensitive to alcohol. There is a correlation between the increase in phosphorylated tau with long-term changes in several genes known to play a role in immunoinflammatory responses.

Presentation Time: 9:25-9:45

Home University: UNC-Chapel Hill

Research Mentor: Sharon P. Holland, American Studies

Program: McNair

Research Title: God Loves Women, and I Do Too: Black Queer North Carolinian Women’s and Nonbinary Folks Engagement with Religion and Spirituality

As a Black queer woman, Mahogany Mckoy was averse to the preachings she experienced as a child that being queer and certainly transgender was a sin. As a child, she didn’t understand why this was a factor and walked away from Christianity throughout high school. Mckoy’s story is similar to the story of other Southern Black queer women and nonbinary people that experienced heterosexism, transphobia, and rigid gender roles in the church. Through oral history interviews, I’ve found that Mckoy and 5 other young North Carolinian Black queer women and nonbinary people have moved away from Christianity and organized religions toward practices that are rooted in other forms of spirituality. This shift also coincides with their coming out stories, self-exploration, and interrogation of their gender and sexual identities. Most of the participants found that spirituality separate from organized religion has allowed them to have more freedom in the practice and expression of their spiritualities and identities. How are North Carolinian Black queer women and nonbinary people interacting with religion and forms of spirituality? How do their identities affect these interactions? This narrative paper illustrates the similarities and key differences among vastly different North Carolinian Black queer women and nonbinary people to see how their gender, race, and sexuality have played key roles in influencing their spiritual and religious journeys.

Presentation Time: 9:25-9:45

Home University: UNC-Chapel Hill

Research Mentor: Dr. Todd Cohen, Neurology Department

Program: SURF

Research Title: Investigating the Phosphorylation of HDAC6 in Protection Against Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by the accumulation of waste proteins, often referred to as tangles, which are considered the primary contributor to neuronal death. The main component of these tangles is tau protein which undergoes modifications that correlate with cognitive decline. Of these modifications, lysine acetylation is particularly relevant as it strongly accelerates tangle formation. Histone deacetylase 6 (HDAC6) is known to remove acetyl groups from tau protein, and thus, serves as a potential modifier for AD pathogenesis. Here, we hypothesize that HDAC6 activity is regulated by specific kinases via phosphorylation at Ser-22. In this study, we performed subcellular fractionation, co-immunoprecipitation, and immunofluorescence approaches using HEK-293 cells. We further investigate which kinases most effectively interact with and phosphorylate HDAC6, and analyze the downstream events of HDAC6 phosphorylation, such as nuclear-cytoplasmic shuttling. Our results showed that the Parkinson’s disease (PD)-relevant kinase LRRK2, and GSK-3, a kinase long implicated in AD progression, exhibited potent kinase activities towards HDAC6 and mediated subcellular translocation of HDAC6. This study highlights potential upstream enzymes of HDAC6 and the succeeding events of HDAC6 phosphorylation. Further investigation of these kinases in disease models could reveal alternative strategies for AD treatment and potentially bridge gaps between AD and PD pathologies.

Presentation Time: 9:50-10:10

Home University: UNC-Chapel Hill

Research Mentor: Rebecca Fry, Gillings School of Public Health

Program: McNair

Research Title: Disparities in the location of Superfund site in the southern United States

Background: Superfund is a federally funded program implemented by the US Environmental Protection Agency (EPA) to clean up hazardous waste sites. The National Priorities List (NPL) consists of Superfund sites that pose significant threats to the environment and human health. There are a total of 193 NPL sites in the states which encompass EPA region 4, in addition to 83 other alternative approach and deleted sites which are not currently on the NPL. The purpose of this study was to assess spatial disparities in the distribution to Superfund sites in EPA region 4, and the demographics of the communities surrounding these sites.
Methods: The 2015-2019 5-year American Community Survey census tract data was used to generate population demographics of communities located within specific proximities of the 276 Superfund sites in EPA region 4. These census tracks and demographics were analyzed using expanding buffer distances (1.0-10.0 miles) from Superfund sites. The correlation between demographic determinants and Superfund site proximity was then evaluated using regression analysis.
Results: Specific sociodemographic characteristics, including black, non-white, poverty, education status and unemployment, were negatively correlated with Superfund site proximity. This relationship was seen inversely in other sociodemographic groups, including white and homeownership, where percentages in these populations increase with distance from Superfund sites.

Presentation Time: 9:50-10:10

Home University: North Carolina Central University

Research Mentor: Ilona Jaspers, Toxicology and Environmental Medicine

Program: 21st Century Environmental Health Scholars

Research Title: Plastic Burn Pit Emissions Generated from Flaming and Smoldering Temperatures Induce Variable Toxicity on Human Nasal Epithelial Cells

Burn pits are areas utilized for military waste disposal through open air combustion. This system was common in Afghanistan and Iraq, where in 2014, almost 60,000 pounds of solid waste was burned daily. Exposure to these emissions may damage respiratory tissues and increase one’s susceptibility to lung and airway diseases. We hypothesized that emissions from combusting plastic, a major components of burn pit materials, would be cytotoxic to human nasal epithelial cells (HNECs) in vivo, and that incineration temperature would affect biological outcomes. Military-grade plastic materials were burned at smoldering (500°C) or flaming (640°C) temperatures in a quartz tube furnace system and collected as condensates in a series of cryotraps. Primary HNECs differentiated at air-liquid interface and 16HBEs were treated with smoldering and flaming plastic condensates at concentrations from 5-20 μg/cm2 on the apical side for 4 hours. Markers of inflammation including IFN-γ, IL-1β, IL-8, IL-13, IL-4, IL-6, TNF-α, and IL-p70 were assessed in basolateral supernatants. Our data indicate that regardless of temperature, emissions from incineration of plastic increase markers of inflammation. Specifically, emissions from burning plastics significantly increased IL-8, IL-1β and IL-6 at various concentrations and temperatures. Other markers of inflammation, although not significant, were all increased by emissions from burning plastic material. These results revealed that inhalation of emissions of burning plastic increases markers of inflammation in human respiratory cells.

Presentation Time: 9:50-10:10

Home University: UNC-Chapel Hill

Research Mentor: Leslie Hicks, UNC Chemistry

Program: SURF

Research Title: Prediction and discovery of small open reading frame encoded polypeptides from Enterococcus faecalis

Recent multi-omic efforts have facilitated the discovery of unannotated small open reading frame encoded polypeptides (SEPs). SEPs are small proteins (< 50 amino acids in length) representing an underexplored class of biomolecules due to the lack of genome prediction software and challenges in identification. However, increasing evidence demonstrates that SEPs play critical roles in cellular processes and serve diverse microbiological functions. Some known SEPs exhibit functions such as promoting pathogenesis, stabilizing protein complexes, and containing antimicrobial properties. Enterococcus faecalis is a ubiquitous member of healthy human gut microbiota with duality as a probiotic commensal as well as an opportunistic pathogen. The absence of pathogen-specific genes or pathogen-specific features suggests that E. faecalis’s virulence is determined by the host-microbe interaction. To this end, we hypothesize that the expression of various SEPs associate with E. faecalis’ transition from a commensal to pathogenic in changing environments. Herein, a six-frame genome translation and smORFinder were used for creating a predicted E. faecalis SEP database. In vivo translation of predicted SEPs is pursued via mass spectrometry.

Presentation Time: 9:50-10:10

Home University: UNC-Chapel Hill

Research Mentor: Gregory Scherrer, Department of Cell Biology and Physiology

Program: SMART

Research Title: Investigating the role of μ opioid receptor in Chx10-expressing neurons

Mu opioid receptors (μ receptors) play a critical role in the effects of opioids, including analgesia, opioid-induced hyperalgesia (OIH), tolerance, withdrawal, and locomotor-related behaviors, but which populations of receptors are the primary mediators of these processes is yet to be determined. Neurons expressing Chx10, a molecular marker specifically expressed by V2a+ pre-motor neurons located in the regions of the ventral spinal cord and brainstem, also express μ receptors. By removing μ receptors in these neurons, we can determine their role in mediating various opioid effects. To this aim, we have quantified these effects using von Frey filaments, hot plate tests, naloxone-precipitated withdrawal, and video recordings of μ receptor-conditional knockout mice (cKO: Chx10Cre/+; Oprm1fl/fl) and wildtype littermates (control mice) after morphine administration. Altogether the data suggest that mechanical and thermal pain thresholds of cKO mice before and after morphine are very similar to those of control mice. However, we have found interesting differences in locomotor-related behaviors. Specifically, morphine-induced hyperlocomotion and straub tail, two very distinct behaviors occurring after morphine exposure, were completely absent in the cKO mice. Thus, the μ receptor/Chx10-expressing neurons likely play a role in hyperlocomotor activity and muscle rigidity caused by morphine. Future experiments will focus on these findings.

Presentation Time: 9:50-10:10

Home University: North Carolina Central University

Research Mentor: Julie Austen, Ariel Everett, FPG Child Development Institute, Early Childhood Technical Assistance Center

Program: McKinney Scholars Program

Research Title: It Takes a Village - The Exploration of Education and the Socioecological Model 

This presentation focuses on various aspects of a child’s life that impact their educational views and experience. However, all the aspects can be categorized into four sections — individual, relationships, community, and societal — using The Socioecological Model. The purpose of this project is to explore those factors using multiple approaches, such as: interviews with community leaders, brief literature review, reviewing data, and conducting a windshield survey of a local school. I have discovered that factors that occur outside of the classroom can have a bigger impact than factors that occur inside of the classroom; this is why it takes a village.

Presentation Time: 10:15-10:35

Home University: UNC-Chapel Hill

Research Mentor: Dr. Rebecca Fry, Department of Environmental Sciences and Engineering

Program: 21st Century Environmental Health Scholars

Research Title: Examining the Effects of Inorganic Arsenic on Chromatin Accessibility in Placental Cells Using ATAC-seq

Inorganic arsenic (iAs) is a ubiquitous toxic metal in the environment known to be detrimental to human health. More than 100 million people, including those in the United States, are at risk of exposure that exceeds the World Health Organization’s recommended limit of 10 parts per billion (ppb). Prenatal exposure to iAs is a global public health concern as iAs can cross the placental barrier and cause genomic and epigenomic perturbations in the fetus leading to developmental and later onset effects. Adverse health outcomes such as low birth weight and cancers have been linked to iAs exposure. In this study, we exposed JEG-3 placental choriocarcinoma cells to varying iAs doses for 24 hours. The Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) was then used to identify open regions of chromatin. We observed that iAs modified the chromatin structure differentially across the genome with potential effects on gene activation or silencing. A 3% difference in chromatin accessibility was observed across the entire genome when comparing the highest dosage to the controls. Future research will investigate the gene-specific locations of chromatin accessibility. Our findings provide mechanistic insight into the toxicity of iAs on human placental cells. These data are relevant to the known effects of prenatal exposure to iAs on fetal development and provide support for the Developmental Origins of Health and Human Diseases (DOHaD) hypothesis.

Presentation Time: 10:15-10:35

Home University: UNC-Chapel Hill

Research Mentor: Amanda Elton, Psychology and Neuroscience

Program: SMART

Research Title: The Affects of Attention deficit Hyperactivity Disorder on Behavioral Measures of Impulsivity

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is often characterized by impulsive behaviors, difficulty holding attention, and hyperactivity. Impulsivity is one symptom that is usually rated as more prominent in those with ADHD in comparison to those without this disorder. The two behavioral tasks commonly used in researching this disorder are delay discounting and the stop-signal task. Previous research has found that there is greater delay discounting among those with ADHD, but the stop-signal task has provided mixed results in regards to impulsivity. These results were more mixed in regards to adult sufferers of ADHD. The current project involves an MRI study and an online study. The goal of these studies is to see if the impulsivity measured in the results will show a future likelihood of alcohol abuse. The online study currently has data from 337 participants in the delay discounting task and 324 participants in the stop-signal task. All participants are 18 to 19 years old and in their first year of college and most participants do not have ADHD. While the focus of the larger project is on impulsivity and alcohol abuse, my project seeks to understand how ADHD affects performance on behavioral tasks of impulsivity in an emerging adult sample.

Presentation Time: 10:15-10:35

Home University: UNC-Chapel Hill

Research Mentor: Matthew Redinbo, Chemistry

Program: SURF

Research Title: Investigating the Structural and Functional Diversity of Azoreductases Across the Human Intestinal Microbiome

Azo-linked compounds are ubiquitous across foods, textiles, paints, and cosmetics, as well as prodrugs that treat Inflammatory Bowel Disease (IBD). Azoreductases (AzoRs) are a family of enzymes produced by bacteria residing in the human gastrointestinal tract that reductively cleave these azo linkages; however rates of activity differ dramatically depending on the species of origin. Through metagenomic analyses, our lab has identified over 100 putative azoreductases across the human gut microbiome. In this study, we compare two novel azoreductases from Klebsiella pneumoniae (KpAzoR) and Clostridium marseille (CmAzoR) to the well-characterized Escherichia coli azoreductase A (EcAzoRA). We determined the catalytic efficiencies of these enzymes in metabolizing four sterically diverse azo dyes: methyl red, amaranth red, acid orange 7, and brilliant black. Then, we used in silico modeling to compare the structures of these enzymes in the context of their observed activities. We show disparate catalytic efficiencies across our panel of azoreductases and identify key active site differences that may account for the observed differences in activity. In future studies, we aim to characterize more azoreductases and their activities with prodrug substrates to pinpoint the azoreductases integral to the treatment of IBD. Exploring these structural and functional differences can help us better understand how azoreductases differentially activate prodrugs and may enable the manipulation of these differences for targeted therapeutics.

Presentation Time: 10:15-10:35

Home University: UNC-Chapel Hill

Research Mentor: Rebecca Fry, Department of Environmental Sciences and Engineering

Program: McNair

Research Title: Developing an Environmental Justice Index for Toxic Metal Well Water Contamination in North Carolina

Background. Approximately 2.4 million well water users in North Carolina (NC) are vulnerable to metal contamination because they are not protected by the Environmental Protection Agency’s (EPA) Safe Drinking Water Act (USGS, 2018). The established relationship between social and economic indicators and water quality prompts private well contamination in NC to be examined through an environmental justice lens.
Methods. This paper identifies locations in NC where minority and low-income populations experience elevated exposure to well water contaminated with toxic metals. Geocoded well water test results, from 1998-2019 (n=117,960), and American Community Survey estimates for 2019 were used to derive Environmental Justice (EJ) Indexes at a census tract level for arsenic, cadmium, lead, and manganese. This approach mirrors the EPA’s national EJ Index model which combines environmental and demographic data for a single location.
Results. A wide range of EJ Indexes (n=8,152) were determined. Census tracts in Union, Pitt, Guilford, and Sampson counties had the highest EJ Index for arsenic, cadmium, lead, and manganese, respectively.
Conclusions. The EJ Indexes constructed in this study can be used by public health professionals to prioritize remediation efforts in EJ communities that demonstrate excess risk in well water contamination.

Presentation Time: 10:15-10:35

Home University: North Carolina Central University

Research Mentor: Iheoma Iruka, Leslie deRosset, Equity Research Action Coalition

Program: McKinney Scholars Program

Research Title: Equitable Policies That Positively Impact Black Families and Children Prenatal-to-3

COVID-19 and the racial reckoning over the last 24 months has brought attention to structural racism and system inequities faced by Black people in the United States. Black children and families’ optimal development are being threatened on a daily basis, visible with the racial disparities in health, income, and education. The objective of this presentation is to examine policies that support the health and development of Black children and families, especially mothers and their babies. Through the lens of social determinants of health and racial disparities, this presentation will connect the complex factors that link race, social context, and policy. This presentation identifies prenatal-to-3 policies that demonstrate effectiveness at creating the conditions in which Black families and their children can thrive. This presentation will highlight the following policies: Prenatal Health and Emotional Well Being, Healthy and Equitable Births, Sufficient Household Resources, Nurturing and Responsive Child-Parent Relationships, and Nurturing and Responsive Child Care in Safe Setting. This presentation will illuminate some of the disparities that effective policies are seeking to mitigate to ensure a healthy future for Black families and children.

Presentation Time: 10:40-11:00

Home University: UNC-Chapel Hill

Research Mentor: Rebecca Fry, Department of Environmental Science and Engineering

Program: 21st Century Environmental Health Scholars

Research Title: Exploring chemical targets within the Robust Placental Clock using the Comparative ToxicoGenomics Database

The Robust Placental Clock (RPC) is an epigenetic clock based on placental tissue DNA methylation found to be a highly accurate estimator of gestational age. Through its use of 558 individual CpG sites to enhance gestational age prediction, the Robust Placental Clock has been found to indicate a median error of less than one week. Due to its recent finding, however, the effects of chemical toxicants on the Robust Placental Clock have not yet been explored in-depth and literature on the topic itself is limited. By conducting a deep-dive of the Comparative ToxicoGenomics Database, the goal of this project is to build a “Robust Placental Clock Chemical-Gene interactions” database that explores the known effects of chemicals on the genes that are a part of the clock in an attempt to identify major gene targets of toxicants within existing literature that are also a part of the Robust Placental Clock. Through the identification of major gene targets within the clock, it is anticipated that the direction that future research should take in exploring the effects of chemical toxicants within the Robust Placental Clock will be elucidated.

Presentation Time: 10:40-11:00

Home University: UNC-Chapel Hill

Research Mentor: Dr. Hua Mei, Dept. of Ophthalmology

Program: SMART

Research Title: The Role of a Small Molecule in Facilitated Corneal healing

The cornea contains five layers: epithelium, Bowman’s layer, stroma, Descemet’s membrane, and endothelium. External damage to epithelium does not generally lead to scar formation, however, if the damage reaches corneal stroma, a scar will form, negatively impacting vision. Stroma cells have been observed to secrete certain small molecules in response to wounding. One such molecule is Protein X, our molecule of interest. We are interested in determining if Protein X can facilitate healing of corneal wounds that have reached the stroma, without leaving scars. The experiment begins with the surgical application of wounds to the corneas of mice and immediate introduction of the molecule of interest via local injection. Subsequent to an incubation period, tissue samples are harvested and microscopy slides are prepared. The sample slides are then stained using immunohistochemistry, which attaches marker antibodies to proteins known to be involved in the corneal healing process. The sample slides are then viewed via fluorescence microscopy, which reveals the concentrations of these marker proteins in the region of the wound, thus allowing observation of the healing activity. These images are recorded and processed by software that overlays the images to quantify the protein expression. Reportable results from this study are still pending. Upon the conclusion of the mouse model study, we intend to follow up with a replicative study utilizing human corneal tissue.

Presentation Time: 10:40-11:00

Home University: UNC-Chapel Hill

Research Mentor: Shu Wen Ng, Nutrition

Program: SURF

Research Title: Urban and Rural Purchasing Patterns of SNAP Participants in North Carolina

Urban and rural residents have different food environments and different resources available to them. Research has shown that healthy foods are more likely to be more expensive in rural areas and less accessible. SNAP beneficiaries may face particular barriers from purchasing healthy foods due to their limited budgets. We used existing de-identified transaction data from a large grocery chain with nearly 500 stores throughout North Carolina to look at SNAP purchases from rural vs urban stores from October 2019 through December 2020. We are interested in understanding if rural stores contribute to more/less healthy purchases (fruits and vegetables with and without additives) or unhealthy purchases (sugary beverages) by SNAP participants compared to urban stores. We will also investigate if these differences widened or narrowed since COVID. We have organized the large amount of transaction level data, conducted data diagnostics, layered on auxiliary data and created relevant measures/variables for analyses. We will be conducting descriptive and regression-based modeling over the next month.

Presentation Time: 10:40-11:00

Home University: UNC-Chapel Hill

Research Mentor: Patrick Sullivan, Psychiatry

Program: CSS

Research Title: Assessing Transcriptional and Epigenetic Impacts of Antipsychotics

Schizophrenia is a severe mental disorder that affects ~1% of the population. It is typically diagnosed during adolescence or early adulthood, and characterized by the presence of hallucinations, delusions, and grossly disorganized behavior. Antipsychotics are the primary treatment of these symptoms. Unfortunately, due to side effects, and/or lack of efficacy, about 75% of patients discontinue the use of antipsychotics. This study uses functional genomics approaches to gain mechanistic insight into the transcriptional and epigenetic changes brought about by chronic antipsychotic exposure. We carried out a dosage study (pilot study) using drug-containing chow, to determine the appropriate dose needed to achieve human-like plasma drug levels of commonly used antipsychotics. The study consisted of 8-week old male C57BL/6 mice that were randomized across 3 different treatment groups: haloperidol (1 mg/kg; 3 mg/kg; 5 mg/kg), olanzapine, and placebo (n=4 mice per treatment group). Mice were fed drug-containing chow for a period of 28 days; plasma was collected at 21 days. Body weight was recorded before and after treatment. Haloperidol treatment groups 3 mg/kg and 5 mg/kg were discontinued due to weight loss. After 28 days, mice went through cardiac perfusion, and brain regions were dissected and stored at -80°C. Dosage studies will be followed with larger groups of mice and additional antipsychotics, in order to elucidate the effects of chronic antipsychotic treatment on chromatin structure and gene expression.

Presentation Time: 10:40-11:00

Home University: UNC-Chapel Hill

Research Mentor: Shauna Cooper, Psychology

Program: McNair

Research Title: Arab American Families, Acculturation, and Biculturalism: A Comprehensive Review

Arab Americans are defined as people living in the United States with ancestry from at least one of the 22 states of the Arab League (Member states of the Arab League). There are currently an estimated 3.7 million Arab Americans and the population is growing exponentially, yet there is little research that highlights the unique experiences of this demographic group. Given the consequences of the terrorist attacks on September 11th and the current political climate, where xenophobia and islamophobia are acutely present in U.S. society, Arab Americans have experienced increased discrimination and harassment. This present study is a synthesis of the existing literature on factors that shape family processes among Arab Americans Key focus areas of this review include: 1) historical context of Arab Americans in the U.S.; 2) acculturation and biculturalism; 3) culturally-specific family patterns and practices; 4) ethnic identity development; and 5) potential impacts on the development and adjustment of Arab American adolescents. At the conclusion of this critical review, I provide key recommendations and directions for future research on Arab American families and children.

Presentation Time: 11:05-11:25

Home University: UNC-Chapel Hill

Research Mentor: Andrew Mann, Physics and Astronomy

Program: CSS

Research Title: The Characterization of a Young Exoplanet From the Kepler Mission

Due to various natural processes, planets will change over their lifetime. We can see this in our Solar System, as Mars and Venus show evidence of once liquid water, and Earth shows an evolving atmosphere and terrain. Since their initial discovery in 1992, nearly 4400 exoplanets, residing outside of our Solar System, have been confirmed. However, less than 1% are considered young planets less than 500 million-years-old. Young planet discovery aids in understanding planetary evolution. When comparing younger and older exoplanets, more data will help to create statistically significant results, thus mitigating the effects of outliers. We seek to characterize a known young planet candidate initially considered a false positive. Using neighboring stars’ properties, including kinematics, rotation, color, magnitude, and Lithium abundance, we estimate the stellar association, and thus the host star, to be 80 million-years-old. The planet is orbiting a young analog of our older Sun (5 billion-years-old) in an association overlapping with the Kepler-prime field. By analyzing the light curve, or the star’s observed brightness over time, using a Markov Chain Monte–Carlo based modeling approach taking into account our updated stellar parameters, we estimate the planet to be about twice the size of Earth (1.95±0.10R⊕) on a close-in orbit (19.58 days). Given its age and parameters, this system is valuable for the continual research on the evolution of young systems.

Presentation Time: 11:05-11:25

Home University: UNC-Chapel Hill

Research Mentor: Ian Davis, UNC School of Medicine

Program: SURF

Research Title: Exploring Synergistic Effects of Small Molecules in Ewing sarcoma

Ewing sarcoma, the second most common bone cancer in children and young adults, is driven by a chromosomal translocation that generates the critical fusion oncoprotein EWS-FLI11. EWS-FLI1 binds to specific genomic loci where it increases chromatin accessibility. EWS-FLI1 results in nucleosome depletion at targeted sites, and silencing EWS-FLI in cells results in decreased chromatin accessibility at EWS-FLI1 target sites. Previously, the Davis Lab demonstrated that small molecules can also decrease chromatin accessibility at EWS-FLI1 target sites (Pattenden et al). Furthermore, a small molecule modulator of EWS-FLI1 protein stability, 7ai, has been recently identified, but its effects on chromatin accessibility have not been as well characterized (Su et. al). As these compounds have different mechanisms of action, we asked whether synergy might be achieved by combining compounds with effects on chromatin accessibility . Using FAIRE-qPCR, I will characterize the effects of 7ai on chromatin accessibility at EWS-FLI1 target loci alone and in combination with UNC0621 and Varinostat, small molecules that decrease chromatin accessibility at these sites. As these compounds also have effects on Ewing sarcoma cell proliferation, I will use two proliferation assays, the WST assay and the real-time microscopy using the Incucyte to assess the effect of the compounds singly and in combination on the metabolic activity and proliferation of Ewing sarcoma cells, respectively. Ultimately, this drug discovery research not only aids to understand the mechanism of EWS-FLI1, but it also has the possibility to increase Ewing Sarcoma survival rates

Presentation Time: 11:05-11:25

Home University: UNC-Chapel Hill

Research Mentor: Frank Conlon, Biology

Program: SMART

Research Title: A Proteomics Based Approach to Determine the Role of the Cardiac Neural Crest

Outflow tract abnormalities are the most frequent congenital heart defects. These are due to the absence or dysfunction of the two main cell types: neural crest cells and secondary heart field cells. In a developing embryo, the neural crest is a transient structure that allows for neural crest cells to migrate and give rise to different organs. Neural crest derivatives originate from four major segments: cranial, cardiac, vagal, and trunk. cKit is a receptor tyrosine kinase that marks several cell lineages, including neural crest, hematopoietic, and germ-line stem cells. Signaling from cKit is crucial for normal hematopoiesis, pigmentation, fertility, gut-movement, and some aspects of the nervous system. Fate mapping experiments using novel cKitCreERT2 mouse lines revealed cKit positive cells give rise to all expected cardiac neural crest derivatives, including the outflow tract of the heart, tunica media of the aortic arch, cardiac and aortic valves, atria, and inflow tract. There are multiple cKit mutations in the mouse. One mutant, cKitW44, exhibits defects in melanocytes and germ cell development, but has completely normal blood values. Since cKit positive cells give rise to cardiac neural crest derivatives, we sought to determine if cKitW44 mice exhibit neural crest derived cardiac defects using quantitative mass spectrometry based approaches and histological examination. We further aim to explore if there are biological sex differences in cardiac tissue of these cKitW44 mice.

Presentation Time: 11:05-11:25

Home University: North Carolina Central University

Research Mentor: Ilona Jaspers, Center for Environmental Medicine, Asthma, and Lung Biology

Program: 21st Century Environmental Health Scholars

Research Title: Characterization of Cytokines Secreted by Human Monocyte-Derived Macrophages Grown on Transwells

E-cigarettes are used by millions of people, but we do not understand their full toxicity. To study the effects of e-cigarettes on airway macrophages, we are using a macrophage model derived from human blood monocytes. Before these cells can be used in an e-cigarette exposure, they have to be characterized for markers usually presented by airway macrophages. We have previously characterized these cells after culturing them in regular cell culture dishes. However, for relevant e-cigarette aerosol exposures, these cells need to be grown on Transwell inserts to facilitate the exposure. The objective of this study is to compare biomarkers secreted by macrophages grown in regular cell culture dishes with those grown on Transwell inserts. To do so, we measured the secretion of three cytokines (IL-6, CCL17, CCL18) by human blood monocytes differentiated into three types of macrophages (M0, M1, M2). We found that on Transwells human blood monocytes differentiated into M1 type macrophages secreted significantly more IL-6, and we found that M2 type macrophages secreted significantly more CCL17 and CCL18. This is the same pattern we previously observed when growing the cells in regular dishes. These data indicate that human blood monocytes differentiated into M1 and M2 type macrophages have similar phenotypes when cultured in regular dishes and on Transwells, suggesting that they present a suitable model for studying the effects of e-cigarettes on macrophages.

Presentation Time: 11:05-11:25

Home University: UNC-Chapel Hill

Research Mentor: Brianna Vickerman, Chemical Biology and Medicinal Chemistry

Program: McNair

Research Title: Assessment of Loading Tissue Plasminogen Activator into Human Red Blood Cells for the Improved Treatment of Cardiovascular Diseases

Due to the unfortunately ubiquitous and deadly nature of cardiovascular diseases by blood clots, especially strokes and myocardial infarctions, the matter of finding effective treatments is of high priority. Tissue plasminogen activator (tPA) is the only drug treatment that is FDA approved to break up blood clots. Despite tPA being considered the gold standard for clot dissolution, this protein therapeutic has severe drawbacks including a short treatment window and deadly off-target effects due to high dosage requirements. From previous experimentation, red blood cells (RBCs) were found to be excellent carriers to protect therapeutics from premature clearance in vivo. Encapsulating tPA inside of RBCs could reduce side effects and allow less therapeutic to be administered overall, ultimately increasing the safety and utility of this treatment. We investigated two methods of loading tPA into RBCs, one using a direct high salt addition to restore the cells to isotonicity while the other used a more gradual resealing process. The purpose of this study was to determine which method resulted in a higher internal concentration of tPA and greater consistent loadings on different days. Data was collected using an Invitrogen ELISA kit. The results indicated that the direct method is preferred due to the lower level of variability in the amount of tPA loaded despite the decreased tPA amount loaded. Further experimentation is ongoing to substantiate these preliminary findings.

Presentation Time: 11:30-11:50

Home University: UNC-Chapel Hill

Research Mentor: Andrea Hussong, Psychology

Program: McNair

Research Title: The Role of Indirect Exposure to Police Violence in Black Adolescent Suicidality

Exposure to racism may negatively impact psychological well-being among Black adolescents, for whom suicide rates have risen within the past decade. Using data from public data archives (i.e., the Youth Risk Behavior Survey and the Mapping Police Violence database), the association between indirect exposure to racism due to living in a state with higher police killings of Black Americans and youth self-reported suicide risk and behavior, particularly for Black youth, was tested. The analysis sample included 6201 Black and white high school students (22.4 % Black; 48.4% Male). Results of six multilevel models showed that indirect exposure to police killings of Black individuals was not significantly predictive of suicide risk and behavior, but when indirect exposure was defined as the rate of Black people killed by police in a state, Black participants who lived in states with higher rates were more likely to report suicidality in comparison to white participants living in those states. Findings indicate that police violence against Black Americans may negatively affect Black adolescent mental health.

Presentation Time: 11:30-11:50

Home University: UNC-Chapel Hill

Research Mentor: Dr. Rebecca Fry, Department of Environmental Sciences and Engineering

Program: CSS

Research Title: Epigenetic Impact of PFOS on JEG-3 Placental Cells via ATAC Sequencing and RNA Sequencing Analyses

Environmental chemicals amount to a large portion of the exposures an individual experiences over their lifetime. Exposure to per- and poly- fluoroalkyl substances (PFAS) have been shown to negatively affect the health of vulnerable populations such as pregnant women and the developing fetus. Recently, perfluorooctane sulfonic acid (PFOS) in particular has become a major chemical of interest due to its ubiquity and persistence in the environment due to its chemical stability. PFOS is especially of concern in North Carolina, as samples 14 times greater than the U.S. Environmental Protection Agency’s health advisory have been found in sewage treatment plants. Exposure to PFOS and other per fluorinated chemicals are associated with adverse health outcomes, such a low infant birth weight, and pre-eclampsia. The goal of my study is to understand the impact of PFOS exposure on JEG-3 choriocarcinoma cells through ATAC sequencing and RNA sequencing analyses, which use a high through-put sequencing approach to identify open areas of chromatin and gene expression, respectively. More specifically, we aim to investigate the impact of per fluorinated chemicals on the epigenome through changes in chromatin structure. Ultimately, the genomic differences between the open chromatic regions of the exposed and unexposed cell populations could help inform the association between prenatal PFOS exposure and the relating negative health outcomes.

Presentation Time: 11:30-11:50

Home University: UNC-Chapel Hill

Research Mentor: Dr. Yuliana Rodriguez-Vongsavanh, School of Education

Program: McNair

Research Title: Examining Differences in Family Empowerment Among Hispanic and White Families of Children with Autism

Given the scarcity of current research addressing the needs of Hispanic children with autism and their families, the purpose of the current study was to examine the impact of ecological microsystems on outcomes for Hispanic students with autism based on their caregivers’ feelings of family empowerment. Differences in family empowerment among Hispanic and White families of children with autism were observed, as well as potential predictors of family empowerment. This study used data collected by the Center on Secondary Education for Students with Autism Spectrum Disorders (CSESA), in which parent participants (N=296) volunteered to complete a variety of surveys and interviews. Family information including household income, caregiver education, and minutes per month of support services were utilized to test their predictability of family empowerment levels, and differences across Hispanic and White families were examined. Findings pointed to the important role that ethnicity can play in predicting family empowerment. However, further research is needed to better understand the experiences of Hispanic families of children with autism, as well as their cultural perspective on family empowerment. This study highlights important implications for researchers, school partners, as well as practitioners to consider in working with Hispanic families of children with autism.

Presentation Time: 11:30-11:50

Home University: UNC-Chapel Hill

Research Mentor: Alain Burette, Neuroscience

Program: SMART

Research Title: Expression of the psychiatric risk gene transcription factor-4 (TCF4) in the developing macaque neocortex.

TCF4 is associated with a range of neurodevelopmental and psychiatric disorders, including autism, schizophrenia, and Pitt-Hopkins Syndrome (PTHS). Although necessary to decipher TCF4 biology and guide future therapeutic approaches, our knowledge of TCF4 expression in the developing brain is still limited, especially in primates. Here, we combined in situ hybridization and immunohistochemistry to characterize TCF4 expression in the rhesus macaque neocortex from gestational day 50 to 5 years of age.
We detected both Tcf4 transcript and TCF4 protein throughout the developing neocortex. However, both were most abundantly expressed in layers II and IV, contrasting with the uniform distribution previously reported across the mouse neocortex.Our experiments point to other differences. Whereas TCF4 is expressed in mouse astrocytes, we found barely detectable Tcf4 transcript and no detectable TCF4 protein macaque astrocytes. In conclusion, our data point to unexpected and potentially significant differences between TCF4 expression in mice and primates neocortex.

Presentation Time: 11:55-12:15

Home University: UNC-Chapel Hill

Research Mentor: Bob Duronio, Biology

Program: McNair

Research Title: Genotypic and Phenotypic Characterization of mutations in Drosophila melanogaster CG8569 which encodes a putative ortholog of the human epigenetic regulator ZMYND11

Mutations in the human ZMYND11 gene have been postulated as the cause of neurodevelopmental disorders such as autosomal dominant intellectual disability 30, the 10p15.3 microdeletion syndrome, and autism spectrum disorders. ZMYND11 encodes a nuclear protein that specifically binds variant histone H3.3 and regulates gene expression at the transcriptional level. However, the molecular mechanisms of action and the functions of ZMYND11 disrupted in human disease remain unknown. One approach to learn more about ZMYND11’s molecular behavior is studying its orthologous gene in a model organism. Our lab is investigating whether the Drosophila melanogaster CG8569 gene encodes an ortholog of human ZMYND11. The purpose of this study was to characterize a transposon insertion allele of CG8569 (CG8569EP1182) both genotypically and phenotypically. We found that the EP1182 transposon was inserted into the coding region of CG8569 and thus should disrupt its function. Nevertheless, we found that gene expression still occurs from the CG8569EP1182 mutant allele and that CG8569EP1182 mutant flies are viable, although they demonstrated reduced longevity when compared to non-mutant flies. To ask whether CG8569EP1182 mutants had neurological defects we measured several parameters of movement in developing CG8569EP1182 larvae. No statistically significant differences were observed in crawling length, crawling time, and crawling speed between mutant and wildtype flies. Together, this study shows that the mutant allele CG8569EP1182 impairs fly longevity but does not affect locomotion in larvae.

Presentation Time: 11:55-12:15

Home University: UNC-Chapel Hill

Research Mentor: Kathleen Gray, UNC Institute for the Environment

Program: 21st Century Environmental Health Scholars

Research Title: Setting up a Wastewater Monitoring Program in North Carolina: Learning to Go with the Flow During a Pandemic

In January 2021, North Carolina began monitoring COVID-19 levels in wastewater at eleven wastewater utilities throughout the state. Influent samples were collected twice a week by wastewater plants and analyzed at a UNC laboratory by droplet digital polymerase chain reaction (PCR) to measure the level of SARS CoV-2, the virus that causes COVID-19. Epidemiologic analysis of trends was conducted by state and national scientists and data were published to the public. These data allow local and state health departments to quickly implement public health actions, such as increased testing, vaccination clinics, and public communication. Due to the large amount of data collected and the number of partners involved in the process, determining a method to collect and securely store the results was critical to the program’s success. In response, we created a relatively easy to use, relational online database using REDCap for participating laboratory staff and epidemiologists. Our team also investigated whether precipitation events correlated with increased influent flow on sampling days. To examine this, influent flow and daily precipitation were graphed to visualize trends for the eleven sites. Our results show that precipitation events often coincided with higher influent flow, suggesting higher levels of infiltration by rainwater. This potentially correlates with a dilution of the gene copies per person suggesting an underestimation of COVID-19 levels, however, more research is needed.

Presentation Time: 11:55-12:15

Home University: UNC-Chapel Hill

Research Mentor: Jonathan Berg, Genetics

Program: SMART

Research Title: Variants that cause Hemophilia A and B: An exploration through Hypothes.is

To determine which genetic mutations, or variants, are most relevant to patient care in the use of precision medicine, evidence for variant pathogenicity evaluation must be analyzed from existing scientific literature in a process known as variant curation. Hypothes.is is a web annotation tool that allows users to annotate scientific literature, contributing to variant curation. The objective of my project is to create annotations, through Hypothes.is, for the F8/F9 coagulation factor genes that will aid variant curation and correlate the type of variant with the severity of Hemophilia A or B, inhibitor status, and assay discrepancy. The procedure involves annotating relevant information, utilizing tags, about patient(s) in the literature; their sex, age, ethnicity, gene variant, disease assertion, phenotype severity, presence of inhibitory antibodies, and assay discrepancy, if reported. In all of the annotations across multiple papers, there were mild, moderate, and severe cases harboring unique variants. Additionally, cases were categorized based on inhibitor status and assay discrepancies. Since the pool of scientific literature is so vast, this project has considerable room for expansion as there are several more variants and correlations to discover. After annotating several case reports and series, I have learned how vital annotation is to variant curation and our understanding of the role of pathogenic variants in disease.

Presentation Time: 11:55-12:15

Home University:

Research Mentor: Rachel Force, Psychiatry

Program: SURF

Research Title: Use of Transcranial Alternating Current Stimulation for the Treatment of Major Depressive Disorder

Major depressive disorder (MDD) is a common, severe psychiatric illness that has a lifetime prevalence of about 16.6% in adults. Patients with major depression respond to antidepressant drugs; however, approximately one-third of these patients remain treatment-resistant after adequate trials of multiple monoamine-based therapies. Treatment-resistant depression is a difficult condition to treat and has an impact on medical comorbidities such as heart disease, cancer, thyroid disease, manifestations of impending relapse, and genetic vulnerability. To combat this, we wanted to further explore the efficacy of alternative treatment methods with transcranial alternating current stimulation (tACS).

MDD has been associated with increased alpha oscillations (8-12 Hz) in the left dorsolateral prefrontal cortex. Therefore, targeting and reducing alpha oscillations in this area could prove beneficial to patients with MDD. Targeted stimulation modalities, such as tACS, can directly engage and selectively modulate oscillations through the application of weak electric currents to the scalp. In addition, tACS has mild side effects, and no serious adverse events have yet been reported. A recent pilot study showcased the preliminary efficacy of tACS to decrease alpha oscillations, but the neurophysiological mechanism of action of how tACS caused this change is still unclear.

This presentation will showcase how we hope to better understand the mechanism of action of tACS in MDD patients. This can be primarily understood with high-density EEG measurements taken before and after every stimulation session. For this study, eligible patients will participate in 5 consecutive 40-minute tACS stimulation sessions, with either sham or 10Hz (alpha) stimulation. In addition to the stimulation session, I will help collect eyes open Resting-State EEG (RSEEG) recordings immediately before and after the 40-minutes of stimulation. This will help determine the immediate after-effects of tACS on brain activity, specifically on alpha oscillation power. If a direct relationship between tACS and alpha power is established, then noninvasive therapies can be considered as a reliable treatment option to alleviate symptoms several symptoms in MDD patients.

Presentation Time: 12:20-12:40

Home University: UNC-Chapel Hill

Research Mentor: Kathleen Gray, UNC Institute for the Environment

Program: 21st Century Environmental Health Scholars

Research Title: Occupational Health and Industry in Confirmed COVID-19 Cases in North Carolina

Worker protection is important to keeping our economy and society running. We aim to study occupational and behavioral circumstances leading to COVID-19 exposures in North Carolina workplaces, as part of a pilot project by the National Institute of Occupational Safety and Health (NIOSH). Our survey will be used to inform workplace interventions for COVID-19 infection and prevention control. We called confirmed COVID-19 positive individuals from a randomly sampled list from the NCOVID surveillance system (02/15/2021-07/15/2021). Inclusion criteria was anyone 18-64 years old, living in NC, who was working outside the home during the 2 weeks prior to illness onset. Healthcare workers were excluded from the survey. Our goal was to complete over 100 interviews with adults infected with SARS-CoV-2. Out of 551 calls, the response rate was 33.3%, while the survey completion rate was 14.2%. Survey respondents were 55.1% White, 14.5% American Indian/Alaska Native, 1.4% Asian, 29% Black/African American. Women accounted for 46.1% of respondents, while men accounted for 52.6% (1 gender not identified). 22.4% of workers did not receive paid time off for COVID-19 illness, with an average of 9.5 workdays missed. Employee health must be a high priority during pandemics since workplaces may be high-risk settings for infections. Unfortunately, our interview goal was not met, however statistical analysis was still conducted. Instituting policy changes that mandate paid time off for illness may be an effective way to prevent spread of COVID-19.

Presentation Time: 12:20-12:40

Home University: UNC-Chapel Hill

Research Mentor: Dr. Eva Telzer, Psychology

Program: McNair

Research Title: Investigating the Mediating Role of Brain Activation in the Relationship Between Racial Discrimination and Adolescent Risk-Taking Behaviors

Racial discrimination greatly impacts the mental and physical well-being of an individual. Adolescents who identify as racial minorities may be especially vulnerable to the effects of racial discrimination because of the significant neurodevelopmental and social changes that occur during adolescence. Previous studies have shown discrimination may influence risk taking behaviors, however no study to date has assessed the impact of the brain in explaining this relationship. The current study assessed the mediating role of insula and temporoparietal junction (TPJ) activation in the relationship between racial discrimination and health risk/prosocial behaviors, two regions that are involved in salience processing and perspective taking, respectively. Participants included 95 racially diverse adolescents (52% female) from ages 14 -16 years. Self-report questionnaires were used to measure experiences of racial discrimination, health risk behaviors, and prosocial risk behaviors. In the functional magnetic resonance imaging scanner adolescents completed a risk-taking task where they took risks for themselves and close others. Using a mediation regression model, results suggested racial discrimination does not predict prosocial/health risk behaviors, nor did insula and TPJ activation mediate this relationship. However, racial discrimination did predict insula/TPJ activation during risk-taking for others. Taken together, findings suggest racial discrimination is associated with the neural processing of how adolescents perceive others.

Presentation Time: 12:20-12:40

Home University: UNC-Chapel Hill

Research Mentor: Jon Abramowitz, Psychology

Program: CSS

Research Title: Parental Needs: Psychological distress and treatment preferences among parents amidst the COVID-19 pandemic

The COVID-19 pandemic has served as a major stressor, impacting millions of individuals across the world. It is likely the stress of the pandemic has had a uniquely strong impact on parents. Over the last year, substantial research has emerged on parental distress and psychological functioning amidst COVID-19. The present literature review aimed to summarize findings regarding the prevalence and severity of psychological symptoms during the pandemic, as well as its impacts on parental functioning (e.g., parenting and child outcomes). A literature search was conducted, and findings synthesized across empirical papers. Overall, findings suggest higher rates of psychological distress, such as depression and anxiety, following the pandemic. Studies have shown that increased psychological distress at this time is associated with increased distress in parent-child relationships, domestic violence, child neglect and maltreatment, and adverse parenting outcomes. This review highlights the significant psychological impact of the pandemic on parents, and how increased distress is likely to have critical impacts on parent-child outcomes. Our findings suggest further study on widespread family support and intervention is essential to decreasing the burden among parents and potential long-term individual mental health and familial relationship issues as the pandemic continues. Prioritizing the treatment of psychological disorders among parents is also of great importance to mitigate the global impact of the pandemic.

Presentation Time: 12:20-12:40

Home University: UNC-Chapel Hill

Research Mentor: Kathleen Caron, Cell Biology and Physiology

Program: SMART

Research Title: Sex Differences in CGRP Response in LECs

Migraine, characterized by calcitonin gene-related peptide (CGRP) upregulation in the cerebral circulation, impacts 15% of the global population, is the second leading cause of years lived with disability, and impacts women 3 times more frequently than men (1,2). Recent studies have demonstrated that CGRP antagonism reduces migraine severity (1). The CGRP receptor components are differentially regulated in a sex-driven manner but regulation of the CGRP receptor is relatively unstudied, especially in the recently re-discovered meningeal lymphatic network (3, 4). The lymphatic system functions to clear wastes from tissues back into the blood and CGRP signaling in the Lymphatic vessels induces lymphangiogenesis and reduced vessel permeability, mediating network density and drainage function (5). My objective is to determine how sex differences in lymphatic endothelial cells (LECs) contribute to CGRP response. First, female and male cells will be treated with CGRP, and LEC barrier tightness will be assessed by vascular endothelial-Cadherin (VE-cadherin) arrangement using immunofluorescence microscopy. Additionally, transcriptional changes of CGRP receptor components following CGRP exposure will be determined using qPCR. Our preliminary data has demonstrated that CGRP increases male lymphatic endothelial cell (LEC) barrier tightness in vitro. The results of these experiments will offer insight into sex differences in lymphatic vessel response to CGRP, perhaps informing migraine treatment strategies.

Presentation Time: 12:20-12:40

Home University: UNC-Chapel Hill

Research Mentor: Ann Marie Weideman, Biostatistics

Program: CFAR

Research Title: Improving statistical analysis in immunology research: An exploration of partial correlation

Partial correlation coefficients are used to determine the strength of an association between two variables while controlling for the effects of confounding variables. Partial correlations range between -1 and 1 and can be computed in the presence of continuous or categorical confounding variables. These correlations are useful in laboratory studies where the sample size is often too small to compute separate correlations within each category of the confounding variable. As a conventional example, we might hypothesize that two biomarkers are positively correlated, but that one (or both) of the biomarkers varies with advancing age and sex. Thus, partial correlation could be used to determine if there exists a direct association between the two biomarkers by controlling for the confounding effects of age and sex. Failing to control for age and sex may result in false evidence of an association between the biomarkers due to contaminating relationships between the confounders and the variables of interest. As part of this short analytics review, we have chosen to review several manuscripts, along with their associated datasets, that could have benefited from reporting partial correlations. Additionally, we have developed a user-friendly web-application that allows users to securely upload their data to compute partial correlations in a point-and-click manner. Together, this manuscript and web-application will help to improve understanding of partial correlation coefficients and allow readers to easily compute them.

Presentation Time: 1:30-1:50

Home University: UNC-Chapel Hill

Research Mentor: Gregory Miner, Cellular Physiology

Program: SMART

Research Title: Construction and Validation of Dimerization Dependent Fluorescent Probes to Visualize Lipid Droplet - Organelle Contacts

Lipid droplets (LDs) are a vital metabolic center of cells. Among other functions, LDs are specialized in storing diverse classes of lipids. LDs serve three critical purposes: LDs are energy reservoirs, a source for building-blocks for the organelle membrane system and are active in communication. In order to fulfill these functions, LDs need to communicate with other organelles. However, the structure of LDs (phospholipid monolayer) is not compatible with regular fusion of bilayer bounded structures. As a result, the way LDs are forced to communicate with other organelles is by creating contact sites with other cell compartments to exchange lipids. However, exactly which lipids are being transferred, the direction of this transfer, and how these LD-organelle contacts are regulated is unknown. The objective of our lab is to study the physiological function of these LD-organelle contacts. To achieve this objective, our lab uses confocal microscopy to study organelle dynamics, contacts, and lipid trafficking within and between cells. We are generating and testing new dimerization-dependent fluorescent probes to visualize LD-organelle contact sites and observe the dynamics of these contacts overtime. We have successfully created the lipid-droplet-mitochondria and the lipid-droplet-peroxisome dimerization probes. Going forward, we will be working on creating the LD-ER, LD-lysosome, and the LD-plasma dimerization probes. Our initial focus will be using our LD-Mitochondria probe to study the effects of metabolic stressors on LD-Mitochondria contacts.

Presentation Time: 1:30-1:50

Home University: North Carolina Central University

Research Mentor: Dr. Rob Maile, Burnett Womack - UNC School Of Medicine

Program: 21st Century Environmental Health Scholars

Research Title: Differences in Estradiol Levels After Burn Injury

The American Burn Association estimates ~450,000 people in the United States will suffer from burn injury each year, which results in ~3,500 deaths per year due to severe immune dysregulation. Female burn patients suffer higher mortality rates compared to males. Estradiol is involved in the regulation of local and systemic interleukin-6 (IL-6) levels, which has been demonstrated by others to positively correlates with poor outcomes following burn. We hypothesize that estradiol levels increase after burn injury and contributes to local and systemic immune dysregulation. We utilized plasma from 1) human burn patients admitted to the North Carolina Jaycee Burn Center and 2) our murine model of burn injury, in which C57BL/6 mice are exposed to a 20% total body surface area burn injury. We measured human estradiol levels 1-3 days after burn injury and murine estradiol levels 3 and 7 days after injury by ELISA. In humans there were differences in levels at these timepoints (p<0.05). In mice we observed a difference in the change in murine estradiol levels between males and females 7 days after injury (p < 0.01). These data suggest burn injury upregulates estradiol in both humans and mice following burn injury whereby this is more robust in females at later stages of burn injury and thus contributing to female-associated poor clinical outcomes. We are currently correlating estradiol levels to IL-6 levels.

Presentation Time: 1:30-1:50

Home University: UNC-Chapel Hill

Research Mentor: Dr. Sheila Kannappan, Physics and Astronomy

Program: Sheila Kannappan - Physics

Research Title: Galaxy Nearest Neighbor Search Methods

Despite their size, galaxies are not the largest structures in the universe. Unless they are isolated, gravity allows galaxies to congregate at different scales in groups, clusters, and superclusters, which make up the large scale structure of the universe. A galaxy’s environment is dependent on the other galaxies around it, so one way to quantify galaxy environments is by identifying nearest neighbors. Two algorithms that accomplish this are called the KD-Tree Search and Cylinder Search methods. KD-Tree builds a binary tree out of a list of coordinates, where the points in the tree are the coordinates of galaxies. It compares the distances between a particular search point and other points in the tree to find the minimum distance. On the other hand, Cylinder Search limits possible nearest neighbors to particular redshift differences and angular separations before computing the distances between galaxies and finding N nearest neighbors. In my presentation I will explain each search method as they pertain to finding the nearest neighbors of galaxies, as well as provide a comparison between the two.

Presentation Time: 1:30-1:50

Home University: Winston-Salem State University

Research Mentor: Shikha Yadav, Health Sciences

Program: ENABLE

Research Title: Factos Influencing the Mortality Rates of Breast Cancer

Breast Cancer is the 2nd most common Cancer in women in the U.S. Our project aims to utilize data mining and analyzation to explore the most common factors influencing the malignancy of breast cancer and its resulting mortality rates. We will explore the causative risk factors associated with the diagnosis of Breast Cancer through a correlational-descriptive design. Based on our extensive analysis, it was revealed that the mortality rates were heavily influenced by three variables: age at diagnosis, tumor size, and tumor stage.

Presentation Time: 1:30-1:50

Home University: UNC-Chapel Hill

Research Mentor: Dr. Amanda Thompson, Nutrition/Anthropology

Program: McNair

Research Title: Who Helped You? Sources of Breastfeeding Support Among Predominantly Low-Income African American Women In North Carolina

Much literature identifies breastfeeding as one of the primary interventions for reducing infant mortality and improving women’s health globally. However, despite the existence and overall success of national breastfeeding intervention programs in the U.S., African American women persistently have lower breastfeeding initiation rates and duration and the highest rates of poor infant health outcomes. The purpose of this paper is to investigate the sources of breastfeeding support utilized by predominantly low-income, African American women in North Carolina. Using data from the Mothers and Others study, we investigated the relationship between maternal characteristics and the sources of breastfeeding support African American mothers reported using while inside the hospital and outside the hospital through bivariate analysis. In addition, the association between significant maternal characteristics and the sources utilized was tested using multiple linear regression. The results of this paper show that women use different sources of support inside and outside of the hospital. These sources vary by women’s marital status, income, amount of college education, and whether they previously had children.

Presentation Time: 1:30-1:50

Home University: UNC-Chapel Hill

Research Mentor: Jason Stein, Department of Genetics

Program: CSS

Research Title: Segmentor: Training a Machine Learning Algorithm to Optimize the Accuracy of Automatic Brain Segmentation

Individuals with autism often have increased head size, or macrocephaly. Previous studies have described periods of premature heightened brain development that are typically followed by stunts in development to be indicative of neuropsychiatric disorders. A novel and more accurate process of diagnosing macrocephaly includes counting the number of nuclei present in the brain by looking at imaging. However, it is currently unfeasible to count all of the neuron’s in a human’s brain; each person has about ~86 billion neurons, showing that it would manually take one individual 430 billion minutes to complete the segmentation. The Segmentor project involves the development of an annotation tool that will automate cell segmentation from 3D brain images to count how many nuclei are present. Currently, the goal of Segmentor is to create an open-source tool so that people can manually trace the brain images and feed the algorithm “good data.” This data will be used to train a deep learning process that will teach the program how to accurately evaluate where nuclei are without needing any additional human input. Therefore, the development and eventual use of Segmentor shows both improvement in how technology can be used for research and also for medical treatment itself. This program will be able to help improve brain segmentation techniques, which could eventually also be applied to various other parts of the body.

Presentation Time: 1:55-2:15

Home University: North Carolina Central University

Research Mentor: Helen Lazear, Immunology and virology

Program: M&I-HBCU SROP

Research Title: The Power of Interferons: Interferons vs. Viruses

Nissi Ficklin
Email: nficklin@eagles.nccu.edu
Mentor’s information: Nick Catanzaro- nick_catanzaro@med.unc.edu (Helen Lazear lab)

The body is full of amazing things that it can do. One of which is fighting off viruses on its own. The innate immune system is the body’s first line of defense, and with the help of interferons this is possible. Interferons are cytokines that tell cells how to fight viruses. Interferons are glycoproteins that are produced by cells to respond to the virus, restrict the continuation of virus replication, and the spread of the virus before the adaptive response is developed. Type I interferons (IFN-α/β) and type III interferons (IFN-λ) are produced in response to viral infection and signal through the JAK/STAT pathway to induce the expression of interferon stimulated genes (ISGs). To test this hypothesis, we first designed and cloned single guide RNAs targeting candidate ISGs into the all-in-one expression vector, pLentiCRISPRv2. All constructs were verified by Sanger sequencing and introduced into an A549 human lung epithelial cell culture model. Cells are currently undergoing puromycin selection to obtain an edited population. Successful ISG knockouts will first be verified by western blot analysis. Zika virus replication will then be assessed in ISG knockout cells by performing multi-step growth curves and virus titrations. A better understanding of the innate immune response to viral infection will help develop novel antiviral therapeutics.

Presentation Time: 1:55-2:15

Home University: UNC-Chapel Hill

Research Mentor: Brian D. Strahl, Biochemistry & Biophysics

Program: SMART

Research Title: Effect of Ada2 SANT Mutations on H3 and H4 Histone Tail Binding

Post-translational histone modifications (e.g., acetylation) are important mechanisms that contribute to gene transcription and expression. Misregulation of gene expression can lead to cancer or be devastating to embryonic development. The SAGA complex (Spt-Ada-Gcn5-acetyltransferase) is a yeast transcriptional co-activator that regulates acetylation of histones. Within the SAGA complex, the Ada2 protein is a transcriptional activator that is required for binding of H3 and H4 histone tails in yeast. Ada2 contains two distinct structural domains: ZZ and SANT. These domains work together to bind H3 and H4 histones. The purpose of this project was to better understand how each domain functions and binds histones independently. To investigate this, point-mutations were made in regions of the SANT domain suspected to be involved in binding the histone tails. These regions of the SANT domain were determined via sequence alignment to identify highly conserved residues, specifically acidic pockets within the SANT domain that work to bind histones. The Ada2 SANT wild type and point mutants were recombinantly expressed, purified, subsequently used in vitro analysis within Escherichia coli and visualized via western blot. Results suggest that triple-point mutations resulted in decreased binding with H3 and H4. Overall, the mutated proteins were unable to fully eliminate histone binding in H3 and H4. In the future, a crystal structure of the protein must be obtained to determine the actual location for histone binding.

Presentation Time: 1:55-2:15

Home University: Durham Technical Community College

Research Mentor: Shikha Yadav, Health Informatics

Program: ENABLE

Research Title: Data and Text Analysis of Potential Risk Factors of Stroke

Abstract: The focus of our project was to utilize data analysis techniques to find a correlation between ten previously identified variables and the occurrence of stroke. Using these techniques, we were then able to draw conclusions on these variables and their influence on the likelihood of stroke. Another objective of the project was to use text mining to analyze documents from a comprehensive literature review and identify the most relevant terms and document similarity.

Presentation Time: 1:55-2:15

Home University: Cedar Crest College

Research Mentor: Miriam Braunstein, Microbiology & Immunology

Program: SOLAR & SURE

Research Title: Clinically Relevant Bacteriophage Adsorption to Mycobacterium smegmatis

Mycobacterium abscessus, a non-tuberculosis mycobacteria (NTM), is an emerging threat to immunocompromised patients and those with underlying pulmonary diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). M. abscessus infections are extremely challenging to treat due to antibiotic resistance. Bacteriophage (phage) therapy has been shown to target drug-resistant pathogens, posing an alternative to antibiotics. Phages are viruses that infect and kill the bacterial cell host. Much is unknown about the kinetics of phage infection of mycobacteria. Thus, in this study we are determining the timing of phage attachment (adsorption) to the bacterial cell to better understand the period of infection and host cell lysis. The first step in the phage life cycle is phage attachment to bacteria, which is a critical step for treating bacterial infections with phages. Using the model organism Mycobacterium smegmatis and phages BPsΔ33HTH-HRM10, Muddy, and D29 HRM GD40, we demonstrated that the phages display poor adsorption in the time frames that were assayed. Additionally, we found that chloroform kills M. smegmatis but has no effect on the infectivity of the phages tested. In applying chloroform to our adsorption assay, we can more easily distinguish free phages from adsorbed phages. By analyzing phage adsorption, we can assess limitations of specific phages. In the future we can select for phage mutants with increased adsorption rates to optimize phage therapy efficacy.

Presentation Time: 2:20-2:40

Home University: UNC-Chapel Hill

Research Mentor: Shikha Yadav, Program Coordinator

Program: ENABLE

Research Title: A Comprehensive Look at Covid-19 Data in Social Media

Social media has played a prevalent role in conveying news, updated data, and public sentiment during the COVID-19 pandemic. Prior research has been conducted in evaluating the impact and the effectiveness of sharing pandemic news and data via social media, specifically gauging the credibility and relevance of the shared news. This study aims to perform a general sentiment analysis of social media users to evaluate their perspectives and their responses to COVID-19 related news and statistics. Text mining functions were used to process and filter out tweets from April 2020 – June 2021, sort them by word usage, as well as group them by sentiment and connotation. Furthermore, various data visualization functions were also implemented to obtain a comprehensive look at Covid-19 tweet data, recurrent phrases, and suggested sentiments. The results showed that more than 60% of analyzed tweets carried a neutral sentiment, followed by approximately 25% positive and 15% negative sentiments. These results suggest that most covid-19 related tweets on social media are non-opinionated or pertain to the sharing of data and news, and that general worldwide sentiment shows a positive throughout the pandemic. More research is needed to ascertain the relationship between data sharing and public sentiment, as well as accommodate for further data that arises as the pandemic continues.

Presentation Time: 2:20-2:40

Home University: UNC-Chapel Hill

Research Mentor: Justin Milner, Microbiology and Immunology

Program: SMART

Research Title: Enhancing the efficacy of chimeric antigen receptor T cells in pancreatic cancer

Antigen presentation machinery is often downregulated on malignant cells, limiting recognition and killing by CD8 T cells. However, tumor cells express tumor-specific surface molecules, such as B7-H3 or mesothelin, that can be detected by chimeric antigen receptors (CAR) engineered on T cells, and thus induce specific killing against the corresponding tumor cells. The objective of this project is to develop systems for manipulating CAR-T cell activity in preclinical mouse models. To do so, we first evaluated an elegant and well-established CAR-T cell system for pancreatic cancer wherein murine pancreatic cancer cells (KPC cells) stably express B7-H3. My project involved setting up an in vitro assay to test the killing efficacy of B7-H3 CAR-T cell in this model to establish a foundation for testing other novel CAR-T cell strategies. Experimentally, activated mouse T cells were infected by retroviruses that encode a murine adapted B7-H3 CAR. Next, transduced B7-H3 CAR- T cells were co-cultured with KPC B7-H3 tumor cells. Finally, the cells were analyzed via flow cytometry to determine CAR-T cell killing efficacy. While the results are pending, we expect B7-H3 CAR-T cells to demonstrate effective and antigen-specific killing of KPC B7-H3 tumor cells. Future studies will investigate the efficacy of new CAR-T systems and begin targeting critical regulators of T cell function to boost CAR-T cell efficacy.

Presentation Time: 2:20-2:40

Home University: North Carolina Central University

Research Mentor: Peggy Cotter, Microbiology & Immunology

Program: M&I-HBCU SROP

Research Title: Burkholderia thaliandensis Contact-Dependent Growth Inhibition Competitions between strains E254 & E264

In nature, microbes use a variety of systems to compete for resources. Burkholderia thaliandensis uses a system called Contact-Dependent Growth Inhibition (CDI) system encoded by the bcpAIOB genes to compete with its neighbors. CDI systems function by delivering a toxin to a recipient cell which then dies unless it is protected by a cognate immunity protein, BcpI. To better understand CDI systems, I studied the CDI systems in two closely related B. thailandensis strains, E264 and E254. E264 has been extensively studied whereas E254 is a new strain to the lab that has a bcpAIOB locus ~97% identical to E264.

We measure the effectiveness of CDI systems through interbacterial competitions where we mark each strain with separate antibiotic resistances and compete them at a 1:1 ratio. Unexpectedly, we discovered that E254 has separate morphologies; both smooth (E254S) and rough (E254R) and that these behave differently in a competition. We also found that E264 lacking the bcpAIOB locus (ΔbcpAIOB) out-competes E254R by a significant margin indicating that the CDI system is not required for competition. Both E264 WT & E264 ΔbcpAIOB compete equally well with E254S. This suggests that either both CDI systems work equally well or that neither is being used. These data indicate that even closely related strains might use CDI systems differently and that further testing is needed.

Presentation Time: 2:20-2:40

Home University: North Carolina Central University

Research Mentor: Dr. Kate Reissner, Psychology and Neuroscience

Program: SPIRE

Research Title: The Role of Nucleus Accumbens Astrocyte Rac1 on Cocaine Seeking Behavior

Despite evidence that illicit drug use is a significant and growing public health concern, limited effective interventions are available. Moreover, there are no FDA approved treatments for psychostimulant use disorders. Accordingly, in order to develop more effective treatment strategies, better understanding of cellular mechanisms of relapse to drug use following abstinence is warranted. Previous studies have shown that astrocytes in the rat brain nucleus accumbens are both structurally and functionally impaired following cocaine self-administration and abstinence. Further, evidence suggests that stimulating Gq-mediated signaling in astrocytes can reduce cocaine seeking. Accordingly, this study was designed to test the effects of manipulating nucleus accumbens astrocyte cytoskeletal dynamics on cocaine seeking. Specifically, we utilized both dominant negative (DN) and constitutively active (CA) variants of Rac1, a mediator of actin cycling located in astrocyte peripheral processes. Rats (N=17) were trained on cocaine self-administration (6h/day for 10 days). Twenty-four hours following the last self-administration session, rats received a Day 1 seeking test, followed by intra-accumbens infusions of either AAV5-Gfap-mCherry, AAV5-Gfap-Rac1DN (dominant negative), or AAV5-Gfap-Rac1CA (constitutively active). Following 25 days of home cage abstinence, rats were subsequently tested again on cocaine seeking behavior. Results will inform the potential utility of astrocyte dynamics in opposing motivation for drug use.

Presentation Time: 2:45-3:05

Home University: UNC-Chapel Hill

Research Mentor: Guochun Jiang, Global Health and Infectious Disease

Program: SMART

Research Title: Kynurenine metabolism induces HIV latency disruption and induces ACSS2-associated histone crotonylation

The Human Immunodeficiency Virus-1 (HIV) and the Acquired Immunodeficiency syndrome (AIDS) it causes remain incurable. Much has been done to reduce the effects and transmissibility of the disease, with antiretroviral therapy (ART) being a prime example. However, it is necessary to establish a method to completely rid the body of latent and residual active HIV. With a “shock and kill” strategy, latent HIV could be disrupted to express viral proteins and be subsequently targeted for clearance by alternate treatments. A previous study suggests that the tryptophan metabolic pathway may offer insight into potential latency reversal mechanisms, where the tryptophan metabolite, kynurenine, was tested in various modified HIV-latent cell lines to disrupt HIV latency. We hypothesize that the regulation of HIV transcription by tryptophan metabolism may be via epigenetic modification of histone tails at HIV LTR. Treatment is administered for 24-72 hours and cells are harvested for flow cytometry and protein extractions. Preliminary results demonstrate that supplement of kynurenine induces has some effect in the expression of HIV gene transcription in both of the HIV latency models. Results of these experiments further elucidate that kynurenine enhances the levels of ACSS2 and AhR, which may induce histone crotonylation. The potential chemical properties and pathways the treatments interact with could be established as an effective strategy to tackle HIV infection and aid in its potential purge from patients.

Presentation Time: 2:45-3:05

Home University: UNC-Chapel Hill

Research Mentor: Anthony Zannas, Psychiatry

Program: SURF

Research Title: The Relation Between Stress-Induced Epigenetic Changes and Cell Morphology

Historically, cellular morphology has been described using non-specific qualitative language and example images rather than quantitative data, limiting its investigation. The novel technologies ilastik and CellProfiler have emerged to solve this issue and allow for the high-throughput analysis of images to yield quantitative metrics such as cell area, perimeter, circularity, and branching using artificial intelligence (AI)-based cell recognition. Here, we created an ilastik and CellProfiler pipeline that focuses on the morphological measurement of IMR-90 fetal lung fibroblasts using composite images generated by the overlay of transmission microscopy and DAPI nuclear staining images. This pipeline has been utilized to compare the stress-based morphological changes induced by cortisol treatment of cells at a physiological level of 100 nm. Stressed and control groups do not differ in cell area, circularity, or perimeter. However, the stressed cells have a shorter average length per projection per cell. Further work is being done to correlate these morphological changes with known epigenetic changes, and to examine the influence of proliferation on them. Broadly, this pipeline is easily expandable to other cell types, meaning that many more morphological changes stand to be investigated.

Presentation Time: 2:45-3:05

Home University: Spelman College

Research Mentor: Michelle Mac, Microbiology and Immunology

Program: M&I-HBCU SROP

Research Title: Epigenetic Regulation of the HPV Viral Life Cycle

Human papillomavirus (HPV) is the most common viral sexually transmitted disease with the lifetime risk of contraction reaching over 80%. High-risk HPV types have been 09` with promoting cervical cancer as well as head and neck cancers. ​​HPVs are non-enveloped, small double-stranded DNA viruses with histone-associated genomes that infect the basal keratinocytes of the stratified epithelium. HPV viral DNA is established within the nucleus of the cell as episomes, then the viral genome is replicated and passed on to daughter cells. Because the HPV viral genome is histone-associated, there is an interest in how epigenetic regulation affects its viral life cycle. Epigenetic regulator SETD2 facilitates the repair of double-strand breaks (DSB) through trimethylation of H3k36me3 that allows LEDGF to bind to H3k36me3 and promote DSB resection. In response to DNA damage, LEDGF recruits the C-terminal-binding protein interacting protein (CtIP) nuclease, which promotes the resection of DSBs by binding to Rad51. The current study was designed to identify whether, CtIP, is needed for productive viral DNA replication by evaluating the effect of a knockdown of CtIP specific shRNA. It is hypothesized that the knockdown of CtIP will lead to reduced viral replication of HPV31+ cells.

Presentation Time: 2:45-3:05

Home University: University of Miami

Research Mentor: Craig Cameron, Microbiology and Immunology

Program: SOLAR & SURE

Research Title: Nucleic Acid Binding by Enterovirus 2C Protein

As seen over the past year, RNA viruses are a threat to human health and enteroviruses are no exception. Enterovirus 2C protein is an ATPase that plays an essential role in viral replication and assembly, making it an attractive target for developing antiviral therapeutics. In this work, we use fluorescence polarization to assess potential interactions of 2C protein with fluorescently labeled nucleic acid. We show 2C protein is capable of binding RNA and DNA, although DNA is unable to stimulate 2C ATPase activity. Our initial experiments were performed with poliovirus, but have shown that these observations extend to other enteroviruses, including Coxsackievirus B3, Enterovirus A71, and Enterovirus D68. Understanding the nucleic-acid-binding mechanism is the first step to developing antiviral therapeutics targeting 2C protein with pan-enterovirus activity, thus protecting the world from the threat of enterovirus outbreaks in the future.

Presentation Time: 3:10-3:30

Home University: Florida Gulf Coast University

Research Mentor: Brian D. Strahl, Biochemistry & Biophysics

Program: SOLAR & SURE

Research Title: SANT Domain Mutations that Give Insight to the Histone Binding Activity

The SAGA(Spt-Ada-Gcn5-Acetyl Transferase) enzymatic complex is a highly conserved complex in eukaryotic organisms from yeast to humans. SAGA is responsible for regulating cellular processes through post-translational modifications(PTMs) on histones (e.g., acetylation, methylation). If malfunctions arise, it can result in the appearance of neurological diseases or cancer. While there’s a great deal of information on the SAGA complex as a whole, the individual contribution of each protein is not well understood, this is specially true for Ada2. Ada2 protein is known for increasing the histone binding activity of the Gnc5 protein, a histone acetylator, however how this happens is unclear. From the Strahl Lab, data showed that the SANT domain of Ada2 binds both H3 and H4. Our goal this summer was to determine which amino acid residues are important for the binding of these histones to the SANT domain. Utilizing point mutations in acidic pockets of the SANT domain, we mutated the amino acids from acidic to basic and to an uncharged amino acid. Once these mutations were in the recombinant plasmid, protein purification, protein pull-down, and western blotting were performed. Preliminary results show that these mutations were not able to eliminate binding of both H3 and H4. Further studies will involve a crystal structure of the current protein to have a view on the exact binding pockets of these histones and mutate those residues.

Presentation Time: 3:10-3:30

Home University: UNC-Chapel Hill

Research Mentor: Jesse Raab, Genetics

Program: SMART

Research Title: The effect of losing a transcription factor on chromatin remodeling complexes

SWI/SNF is a nucleosome remodeling complex that is found in all cells of the body. SWI/SNF plays a crucial role in changing nucleosome spacing and thus allowing transcription to be carried on. In addition, they have tumor suppression activity where it was found that in many cancer cell lines, lack of their expression from a gene mutation that often involves the SWI/SNF complex. Multiple variations of the complex can be assembled based on the inclusion of different subunits, but how these complexes assemble and are targeted to different genes is unknown. ARID1B defines one such variant form of the SWI/SNF complex. The lab has identified an interaction between TEAD4, a transcription factor, and ARID1B, For this project, we hypothesized that in the absence of TEAD4, ARID1B will not be recruited and enhancer activity will change. To investigate this topic, we used CRISPR technology to knockout TEAD4 and see how their loss affects ARID1B binding to the genome, gene expression, and eventually chromatin modifications at target genes.

Presentation Time: 3:10-3:30

Home University: UNC-Chapel Hill

Research Mentor: ManHua Zhu, Neuroscience

Program: CSF

Research Title: Electronic nicotine vapor exposure and central amygdala activity in mice

Nicotine is a highly addictive chemical that has traditionally been consumed by smoking cigarettes. Due to the introduction of new technology such as electronic cigarettes, nicotine vaping has surged in popularity. The rising popularity of vaping necessitates the development of preclinical nicotine vapor exposure models in mice, as well as a better knowledge of the effects of vaping on certain brain regions. The central amygdala (CeA) is a brain region that regulates behavioral and emotional responses to stress or fear reactions. The cellular implications of nicotine vapor exposure on the CeA were investigated using a mouse model of electronic vapor exposure. Adult male C57BL/6J mice were given intermittent vapes of 120 mg/ml nicotine in propylene glycol: vegetable glycerol (PG/VG) or PG/VG control for a single 3-hour session (acute exposure) or 5 daily sessions (repeated exposure). Nicotine vapor exposure increased serum nicotine and cotinine levels in both acute and repeated exposures. Acute nicotine vapor exposure increased central amygdala (CeA) activity in individual neuronal firing as well as cFos expression, a molecular activity marker. Repeated exposure did not produce the same alterations in neuronal activity as acute exposure. This research validated a mouse model of nicotine vapor exposure and added to our understanding of how electronic nicotine vapor has varied effects on CeA neuronal activity.

Presentation Time: 3:10-3:30

Home University: UNC-Chapel Hill

Research Mentor: Bonnie Shook-Sa, Biostatistics

Program: CFAR

Research Title: Assessing Risk of HIV Acquisition in Sub-Saharan Africa

Approximately 37.7 million people globally were living with HIV in 2020. Although sub-Saharan Africa has about 14% of the global population, it is home to two thirds (67%) of people living with HIV. Due to this disproportionate burden of HIV in sub-Saharan Africa, HIV prevention in sub-Saharan Africa has become a top priority to fight against the epidemic. Since 2014, the Population-based HIV Impact Assessment (PHIA) Project has been conducting nationally representative surveys in 15 of the most-affected countries to capture the state of the HIV epidemic. Here, we explain the PHIA’s complex multi-stage sample design and methods for computing estimates of HIV prevalence and incidence. With available datasets from ten countries, we present comparisons of estimates of prevalence and annual incidence of HIV among men and women in these countries.

In sub-Saharan Africa, around 4200 adolescent girls and young women (AGYW) aged 15–24 years became infected with HIV every week in 2020. Because of the high incidence of HIV among this population, our next step is to explore risk factors associated with recent HIV infection among AGYW in sub-Saharan Africa. We plan to use machine learning methods to build prediction models for HIV acquisition that will be used to develop a risk assessment tool for AGYW. This risk assessment tool can be used in HIV prevention efforts.

Presentation Time: 3:35-3:55

Home University: Fayetteville State University

Research Mentor: Gregory Scherrer, Department of Cell Biology and Physiology

Program: SOLAR & SURE

Research Title: Development of Home Cage Self Administration and Conditioned Place Preference (CPP) Assays in Mice for Addiction Studies

Opioids are the most effective treatments for moderate to severe pain, but they can lead to addiction. The μ-opioid receptor (MOR) mediates various behaviors after morphine exposure including analgesia, hyperalgesia, weight decrease, hyperlocomotion, and addiction. Further investigation of morphine addiction is vital for identifying the specific neuronal populations across the nervous system responsible for addiction. In this study, we generated MOR conditional knockout mice (Chx10Cre/+ ;Oprm1fl/fl) where MOR was removed from the Chx10-expressing neurons, and tested these mice using traditional pain assays after morphine administration. We also established two new behavioral tests, the Conditioned Place Preference (CPP) and the Two Bottle Choice (TBC) assays, to measure addiction in mice. We found that MOR cKO mice showed similar analgesia and morphine withdrawal compared to control littermates, suggesting that the Chx10 expressing neurons may not mediate these effects. Using the CPP assay, mice developed a small preference for morphine after three days of conditioning, however the CPP requires further optimization for addiction testing. We successfully built TBC devices- the experiment is ongoing and we will use it to observe home cage self-administration of opioids in mice. We expect mice to self-administer opioids more than water, with time, during the 14-day experimental period. In the future, we intend to use different MOR cKO mice to elucidate which neurons are involved in the mediation of morphine addiction.

Presentation Time: 3:35-3:55

Home University: UNC-Chapel Hill

Research Mentor: Paul Delamater, Carolina Population Center

Program: CPC

Research Title: Estimating Localized COVID-19 Immunity Levels for North Carolina Counties

Since December 2019, COVID-19 continues to be a global pandemic and challenge public health systems worldwide. To end the pandemic, populations must acquire herd immunity by natural infections and vaccination efforts. My presentation addresses the challenges and solutions of modelling immunity levels for North Carolina counties, what those immunity levels mean for residents living in those counties, and ultimately, where the state of North Carolina stands in battling the COVID-19 pandemic.

Presentation Time: 3:35-3:55

Home University: UNC-Chapel Hill

Research Mentor: Channing Der, Pharmacology

Program: CSF

Research Title: YAP1-TAZ-TEAD Inhibition Sensitizes Cells to KRASG12C Inhibition

Mutations in the KRAS oncogene are among the most frequent driver events in human cancers. Following decades of failed efforts, KRAS was considered ‘undruggable’. However, recent efforts in covalently targeting KRAS mutants harboring a G12C mutation has produced the first anti-KRAS therapy to reach FDA approval. That said, acquired mechanisms of drug resistance are certain to limit the long-term effectiveness of G12C inhibition (G12Ci); something that has been reported in the clinic. As such, the search is on for effective strategies by which to sensitize cells to G12Ci. A currently undescribed, mechanism of resistance to G12Ci is the activation of the transcriptional co-activator paralogs, YAP1 and TAZ. Activation of YAP1 has been shown to overcome KRAS addiction in KRAS-mutant cancers. In concordance with these observations, we found that targeting both YAP1 and TAZ significantly sensitizes cells to MRTX1257, analog of the FDA-approved G12Ci MRTX849 (Mirati Therapeutics). As no YAP1/TAZ direct inhibitors exist, a TEAD1-4 dominant-negative construct was utilized to target the TEAD family of transcription factors, the canonical YAP1/TAZ transcriptional partners, as a mean to indirectly inhibit YAP/TAZ activity. We found that inhibition of TEAD1-4 transcriptional activity sensitized cells to G12Ci. We further examined the efficacy of combined TEAD and G12C inhibition using an array of TEAD inhibitors (Vivace Therapeutics) in combination with MRTX1257. This combination produced a highly synergistic reduction in cell viability.

Presentation Time: 3:35-3:55

Home University: UNC-Chapel Hill

Research Mentor: Rahima Benhabbour, UNC/NCSU Joint Department of Biomedical Engineering (BME)

Program: SMART

Research Title: An Investigation of Nanocellulose/Chitosan-Based Injectable Hydrogels

Osteoporosis affects approximately 200 million people worldwide. One in three women and one in five men over fifty years old will experience an osteoporotic fracture. These rates climb with age, and all rates of osteoporosis are expected to increase by 310% in men and 240% in women by 2050. Currently, an autograft, or a bone graft from one part of a patient’s body to a damaged part, is the gold standard treatment to facilitate bone regeneration for osteoporotic bone defects. However, limited supply of available bone grafts, low quality of regenerated tissues, slow healing processes, and potential risks from donor-site complications due to highly invasive surgical procedures remain the main limitations of this treatment option. The use of human mesenchymal stem cell (hMSC) based constructs has been intensively investigated to overcome these limitations and showed promising outcomes in preclinical studies. However, the optimal seeding density of hMSCs in biopolymer hydrogels remains unknown. Thus, hydrogel samples will be encapsulated with 5, 10, and 25 million cells per mL to determine cell viability with a confocal microscope post 24 and 72 hours. The results of the study will provide insight into what effects cell density in the hydrogel scaffolds will have on osteogenesis markers and regenerative outcomes.

Presentation Time: 4:00-4:20

Home University: UNC-Chapel Hill

Research Mentor: Channing Der, Ph.D., Pharmacology

Program: CSF

Research Title: Defining the Role of Mitochondrial Dynamics in Regulating PDAC Cell Sensitivity to ERK Inhibition

Pancreatic ductal adenocarcinoma (PDAC) is driven by oncogenic activation of KRAS in over 95% of patients. Recent evidence suggests that mutant KRAS activation rewires cancer cell metabolism, altering mitochondrial morphology and function. Specifically, activation of the downstream RAF-MEK-ERK effector signaling pathway leads to phosphorylation of mitochondrial fission protein DRP1, which drives mitochondrial fragmentation to support PDAC growth. In contrast, pharmacological inhibition of ERK signaling, using selective ERK1/2 inhibitor (ERKi, SCH227984), causes mitochondrial fusion and inhibits PDAC cell growth. However, the mechanistic basis by which mitochondrial fission supports PDAC proliferation remains unknown. Furthermore, it is unclear whether mitochondrial fusion is required for ERKi-mediated growth suppression. We hypothesized that preventing mitochondrial fusion by silencing mitochondrial fusion proteins OPA1 and MFN1 will yield resistance to inhibition of ERK signaling. To test this, we used two unique siRNAs targeting OPA1 or MFN1, which caused a hyper-fragmented mitochondrial phenotype. Interestingly, we found that loss of mitochondrial fusion in Pa14C cells increased the GI50 concentration of ERKi by ~40% compared to control-treated cells. This suggests that PDAC cells with hyper-fragmented mitochondria may be slightly resistant to ERKi. However, the other PDAC cell line tested (HPAC) displayed, on average, no significant changes in the GI50 concentration of ERKi. Future studies are focused on further characterizing the impact of altered mitochondrial dynamics on PDAC cell sensitivity to inhibition of KRAS downstream effectors.

Presentation Time: 4:00-4:20

Home University: N.C. A&T State University

Research Mentor: Jeffrey Aube, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy

Program: SOLAR & SURE

Research Title: Triazoles as Kappa Opioid Agonists

The United States opioid epidemic is caused, in part, due to the available opioid pain relievers having adverse effects like euphoria. One approach to addressing this is to develop an alternative opioid that does not induce side effects. Opioid receptor agonists may activate multiple pathways. The ability of an agonist to only activate one pathway is known as biased agonism. If a biased agonist is developed that only activates the pain-relieving pathway but not the side-effect pathway, one could potentially avoid the undesired side effects of known opioids. Our lab has been working on a class of compounds called triazoles that are biased agonists that function at the kappa opioid receptor through the G-protein pathway. Previous studies have identified triazoles as active, biased compounds, but with low metabolic stability. This work also suggests that sulfur is a site of metabolic instability. Therefore, we hypothesize that a bioisosteric replacement of sulfur with carbon will increase metabolic stability. In this project, we have successfully synthesized an active, carbon-linked triazole that will serve as the basis for future structure activity relationship campaigns.

Presentation Time: 4:00-4:20

Home University: UNC-Chapel Hill

Research Mentor: Samantha Pattenden, Chemical Biology and Medicinal Chemistry

Program: SMART

Research Title: Testing the effects of Corin on chromatin accessibility in Ewing sarcoma

Ewing Sarcoma is a pediatric bone cancer driven by a chromosomal translocation, which in some cases leads to the expression on an oncoprotein, EWS-FLI1. EWS-FLI1 drives the cancer cells by altering the transcription program and creating aberrantly accessible regions of chromatin. Histone deacetylase inhibitors (HDACi) reverse the Ewing-Specific chromatin accessibility pattern by suppressing transcription of the EWS-FLI1 protein, which in turn stops cancer cell proliferation. Lysine specific histone demethylase inhibition (LSD1i) reverses Ewing sarcoma-specific transcription programs. The overall goal of this project is to test a compound called Corin which is a dual inhibitor with HDACi and LSD1i warheads. We hypothesize that Corin may have a more potent effect on aberrant chromatin accessibility and gene expression than either LSD1i or HDACi alone in Ewing sarcoma cells. Initially, we optimized the cell parameters by plating the appropriate cell numbers per well of a 384-well plate, making sure cells remain viable after compound treatment. We then treated cells with Corin, LSD1, and HDAC for 24 or 48 hours, then the Assay for Transposase Accessible Chromatin (ATAC) was performed followed by the quantitative polymerase chain reaction (qPCR) to examine changes in chromatin accessibility. Currently, the use of Corin as a combination therapy to treat Ewing Sarcoma is a speculative approach. Although with succuss, this could one day be used as a treatment for Ewing Sarcoma.

Presentation Time: 4:00-4:20

Home University: UNC-Chapel Hill

Research Mentor: Channing Der, Pharmacology

Program: CSF

Research Title: Validating gene targets of MYC transcriptional activity in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the third deadliest cancer in the United States with a dismal 5-year survival rate of 10%. 97% of PDAC cases are driven by mutations in the KRAS oncogene, a GTPase that regulates a myriad of signaling cascades responsible for promoting cell growth, proliferation, and metabolism. When mutated, KRAS exists predominantly in its active, GTP-bound state, which allows it to constitutively signal to its downstream effectors and drive PDAC growth. One of the most notable signaling cascades activated by mutant KRAS is the RAF-MEK-ERK MAPK pathway, which has been the target of several small-molecule inhibitors. Unfortunately, resistance to these inhibitors arises quickly, possibly through KRAS-driven stabilization of the MYC transcription factor. MYC is a known oncogene in many cancer types, and its overexpression in PDAC has been well established. While effective pharmacologic inhibitors against members of the MAPK pathway exist, reliable MYC inhibitors have proven more elusive. A tool compound targeting MYC activity, 975, recently showed promising anti-tumor effects in prostate cancer mouse models, but has yet to be characterized in PDAC. Here, to gauge the effects of 975 on MYC activity in PDAC cells, target genes of MYC transcriptional activity were identified. Following acute suppression of MYC by siRNA knockdown, RNA-sequencing and subsequent qPCR analysis of PDAC cells indicated HSPD1, MYBBP1A, and CBL as candidate MYC-driven gene targets in PDAC.

Presentation Time: 4:25-4:45

Home University: UNC-Chapel Hill

Research Mentor: Dr. Gidi Shemer, Biology

Program: SMART

Research Title: Evaluating the Association Between Prenatal Toxic Metal Exposure and Placental DNA Methylation

Toxic metals belong to a major class of contaminants that are ubiquitously present in the environment, representing a threat to human health. Exposure to toxic metals during pregnancy has been linked to adverse outcomes at birth and later in life. During pregnancy, the placenta serves as a mediator between maternal and fetal exposures, as it enhances or reduces fetal exposure to toxicants. Thus, placental epigenetic change in response to metal exposure is important in understanding how such metals impact fetal development and birth outcomes. Here, we sought to evaluate the association between prenatal metal exposure and placental epigenetic marks (i.e placental clock alleles, metastable epialleles, and epigenetic aging). Placental DNA methylation was measured in 411 samples in the previously established Extremely Low Gestational Age Newborns (ELGAN) cohort using Illumina 850K DNA methylation array. Linear mixed effects models were fit to evaluate the overall associations between (1) epigenetic aging, (2) placental CpG sites annotated to clock, and (3) placental CpG sites annotated to metastable epialleles. All models were controlled for maternal smoking status, racism, body mass index, socioeconomic status, alcohol use, age, and gestational age based on their potential to confound associations among placental DNA methylation and metal exposure. These findings of the current study may help explain how metals cause adverse birth outcomes, specifically through modifying epigenetic aging and specific pathway(s) during development. Future studies should evaluate these associations in full term pregnancies.

Presentation Time: 4:25-4:45

Home University: UNC-Chapel Hill

Research Mentor: Brian Conlon, Microbiology and Immunology

Program: SOLAR & SURE

Research Title: Utilizing Palmitoleic Acid to Enhance Bactericidal Activity of Antibiotics in Gram-positive Bacteria

Lack of commercial viability impedes the development of new antibiotics and the last new class of antibiotic was approved in 2003. Therefore, improving the efficacy of pre-existing antibiotics is a promising strategy to address the antimicrobial resistance crisis. Vancomycin is the frontline antibiotic to treat methicillin-resistant Staphylococcus aureus (MRSA), however its poor bactericidal activity results in high treatment failure. Our research shows that palmitoleic acid, an unsaturated fatty acid, synergizes with vancomycin to kill S. aureus in vitro. However, it is still unknown if palmitoleic acid can also potentiate vancomycin killing of other pathogens. The focus of this research is to test the effectiveness of vancomycin and palmitoleic acid in killing seven other clinically relevant Gram-positive bacteria. We find that palmitoleic acid enhances the bactericidal activity of vancomycin against several Gram-positive species. These findings support the use of unsaturated fatty acids as an antibiotic adjuvant for the treatment of bacterial infections and provides evidence for its use as a novel strategy to enhance our current arsenal of antibiotics. Moving forward, the aim of the project will unravel the underlying mechanism of synergy to identify other antibiotic adjuvants.

Presentation Time: 4:25-4:45

Home University: UNC-Greensboro

Research Mentor: Henrik Dohlman, Department of Pharmacology

Program: CSF

Research Title: Detecting Activity of the Yeast Mating Pathway Through GFP

MAPKs (mitogen-activated protein kinase) receive external stimuli to induce various cellular processes such as the cell cycle in eukaryotic cells. Higher order eukaryotic cells such as mammalian cells are more complex, making them harder to study. Thus we use the simple eukaryotic yeast cells as a model to study the MAPK pathway. In the yeast mating pathway, mating pheromone, α or a- factor, activates the MAPK cascade, Ste11, Ste7, and Fus3, that results in mating gene transcription. Depending on the amount of pheromone and the age of the yeast cells, the mating pathway activity levels change. We hypothesize that the mating pathway will become less responsive to mating pheromones as yeast age. To test our hypothesis, we transformed Fus1-GFP plasmid into the yeast cells in order to monitor the mating pathway activity levels upon pheromone induction. We then measure the GFP intensity of the cells which corresponds to the activity of the mating pathway. As a result, the information obtained from this study can be applied to other, more complex eukaryotic cells and also grant a better understanding of cellular mechanisms when considering how cells respond to medications and therapeutics.

Presentation Time: 4:25-4:45

Home University: UNC-Chapel Hill

Research Mentor: Dr. Lee M. Graves, Pharmacology

Program: CSF

Research Title: Activation of Mitochondrial Protease ClpP Inhibits mTOR Activity in Triple Negative Breast Cancer

ONC201 is an anti-cancer imipridone in clinical trials for multiple malignancies. Novel ONC201 analogues (the TR compounds) with greater potency were identified, although the anti-cancer mechanism of these drugs remained poorly understood. The Graves lab recently identified the mitochondrial caseinolytic protease (ClpP) as the target of these compounds and showed that ClpP activation was required for growth inhibition. Because the mTOR (mechanistic target of rapamycin) pathway plays a central role in regulating growth-related cellular processes including protein translation, nucleotide metabolism, and lipid synthesis, I analyzed the effects of TR57 treatment on the mTOR pathway in SUM159, a triple negative breast cancer model. Herein, I demonstrate that ClpP activation inhibits mTOR signaling as shown by loss of phosphorylation of mTOR substrates: eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), ribosomal protein S6 kinase (p70S6K), and ribosomal protein S6 (S6).  Thus, these results suggest that mTOR pathway inhibition may be involved in the reduction of protein synthesis and cell growth inhibition by ClpP activators.

Presentation Time: 4:50-5:10

Home University: N.C. A&T State University

Research Mentor: Jeremy Cribb, Applied Physical Sciences

Program: Richard Superfine - Applied Physical Sciences

Research Title: Adhesion role in Mucociliary Clearance

In the lung, cystic fibrosis (CF) is associated with failed mucociliary clearance (MCC), which can cause infection and inflammation. Past efforts to increase MCC focus on decreasing mucus rheology, but little is understood about mucociliary adhesions involved in MCC. The Superfine lab measures such adhesion forces by pulling on protein-coated magnetic beads adhered to mucus-coated glass substrates modified by silanization, hydrolysis, and protein coupling. For this assay to be successful, homogenous coverage of the substrate is paramount. Here, epifluorescence microscopy was used to analyze for sufficient substrate homogeneity. To measure for even silane deposition, we bound to it 100 nm fluorescent amine-coated beads. Adhesion measurements were made by pulling lectin-coated fluorescent, magnetic 24-micron diameter beads from mucus-coated substrates. Our results indicate even silanization, activation, and coupling. PEG-coated beads (negative control) show a lower detachment force from a mucus-coated substrate than the same beads coated with lectins. These data show the presence of adhesive interactions between lectins and mucus, which is expected, as well as mucus-mucus interaction.

Presentation Time: 4:50-5:10

Home University: North Carolina Central University

Research Mentor: Aaron Anselmo, Pharmaceutical sciences

Program: M&I-HBCU SROP

Research Title: Improving bacterial attachment to the skin

Therapeutic bacteria have recently received attention as a method to increase the health of the skin, as well as treat certain skin conditions like acne. However, therapeutic bacteria cannot colonize the skin in their natural state. To address this, we have developed a method to modify both the skin and the bacteria with complementary chemical groups that click together to improve bacterial attachment. Specifically, we conjugated azide to the bacterial surface and DBCO to the skin using NHS ester chemistry, which reacts with primary amines on both surfaces. First, we confirmed these modifications can successfully be applied to live bacteria using amine-coated 24 well plates. We analyzed bacterial attachment with microscopy and showed significantly increased attachment relative to controls. Next, we developed an ex vivo pig skin model to show that the skin can be successfully modified with DBCO. Finally, we used live human epidermal keratinocytes (HEKa) to see how the bacteria would attach to live cells. Data showed successful modification of the cells, as well as an increase in bacterial attachment after azide modification. Future work will analyze the viability of HEKa cells following bacterial attachment, as well as in vivo testing in a mouse model. This work demonstrates that bacteria and skin can be successfully modified to improve attachment, potentially enabling the use of therapeutic bacteria as a treatment for various skin conditions.

Presentation Time: 4:50-5:10

Home University: UNC-Chapel Hill

Research Mentor: Ben Philpot, Cell Biology and Physiology

Program: SMART

Research Title: “TCF4 expression in the developing Macaque neocortex.”

Pitt Hopkins Syndrome (PTHS) is a genetic disorder resulting from a mutation or
deletion of the TCF4 gene. Individuals with PTHS have different levels of intellectual
disability, speech impairments, seizures, breathing anomalies, and gastrointestinal
problems. Despite TCF4 clinical importance, its biodistribution in the primate brain is still
largely unknown. Therefore, the objective of this project is to analyze TCF4 expression pattern in primates. We used multiple immunofluorescent labeling to map TCF4 expression in
normal prenatal (gestational day 150), neonatal (2 weeks old), and
adult (1 month, 3 months, and 5 years) rhesus macaque brains, focusing on the neocortex where
TCF4 expression is highest. Quantitative analysis shows that TCF4 can be detected in
most neurons across all cortical regions. Interestingly, 10 to 20% of neurons,
concentrating in layer 2 and 4, express high levels of TCF4. This contrasts with the
mouse neocortex where TCF4 expression level is uniformly expressed across all layers. Such difference may prove important for delivering proper TCF4 gene therapy in
humans and point to the importance of furthering our understanding of TCF4 biology in
primates.

Presentation Time: 4:50-5:10

Home University: North Carolina Central University

Research Mentor: Adam Palmer, Department of Pharmacology

Program: CSF

Research Title: Comparisons of Resistances and Sensitivities to Chemotherapies in T-Cell Lymphomas

The Non-Hodgkin’s T cell lymphoma (TCL) patient population consists of several ​cancer subtypes which have been historically treated with a single one-size-fits-all chemotherapy regimen known as CHOP. Several TCL subtypes do not respond well to CHOP, however, as nearly 40% of patients relapse within 2 years of treatment. There is a wide landscape of alternative chemotherapies that promote cures to TCLs in the relapsed and refractory setting, and it is likely that the varied effectiveness of these drugs is due to the broad biological heterogeneity of the overall patient population. We sought to determine which of 28 available chemotherapies are most effective at killing different TCL subtypes. We collected dose response measurements in vitro for three TCL cell lines after three-day chemotherapy treatments. Our results show that the two cell lines of the same subtype (SR-786 and Karpas-299) exhibited similar pharmacological responses to chemotherapies, while the third subtype (KHYG-1) displayed distinct sensitivities and resistances. Generally, drugs of similar mechanisms of action demonstrated consistent patterns of cell killing on the same cell lines, but there are notable differences that might correspond to specific molecular targets of these drugs. These experiments serve as initial categorization for a few diverse TCLs. Further dose response measurements with additional TCL cultures could identify more distinct individual responses to guide precision-based treatment approaches for TCL patients.