SMART Archives - Graduate Student Success

9:00-9:20	Indyya Harvey 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.	Towards Early Detection of Diabetic Kidney Disease Using Contrast Enhanced Ultrasound Perfusion Parameters	SMART
9:25-9:45	Oscar A. Lasserra 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.	Amygdala activation during negative emotional experiences	SMART
9:50-10:10	Valentina Morales 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.	Investigating the role of μ opioid receptor in Chx10-expressing neurons	SMART
10:15-10:35	Makuachukwu Okeke 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.	The Affects of Attention deficit Hyperactivity Disorder on Behavioral Measures of Impulsivity	SMART
10:40-11:00	David F. Parbel 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.	The Role of a Small Molecule in Facilitated Corneal healing	SMART
11:05-11:25	Dain Ruiz 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.	A Proteomics Based Approach to Determine the Role of the Cardiac Neural Crest	SMART
11:30-11:50	Sarah Salvador 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.	Expression of the psychiatric risk gene transcription factor-4 (TCF4) in the developing macaque neocortex.	SMART
11:55-12:15	Dan Tsuma 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.	Variants that cause Hemophilia A and B: An exploration through Hypothes.is	SMART
12:20-12:40	Aisha Siddiqui 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.	Sex Differences in CGRP Response in LECs	SMART
1:30-1:50	Wendy Showalter 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.	Construction and Validation of Dimerization Dependent Fluorescent Probes to Visualize Lipid Droplet - Organelle Contacts	SMART
1:55-2:15	Ashley Aragon 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.	Effect of Ada2 SANT Mutations on H3 and H4 Histone Tail Binding	SMART
2:20-2:40	Kelly Chong 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.	Enhancing the efficacy of chimeric antigen receptor T cells in pancreatic cancer	SMART
2:45-3:05	Eduardo de la Parra Polina 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.	Kynurenine metabolism induces HIV latency disruption and induces ACSS2-associated histone crotonylation	SMART
3:10-3:30	Maryam Dheyaa 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.	The effect of losing a transcription factor on chromatin remodeling complexes	SMART
3:35-3:55	Noah Dover 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.	An Investigation of Nanocellulose/Chitosan-Based Injectable Hydrogels	SMART
4:00-4:20	Alexandra Fraiser 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.	Testing the effects of Corin on chromatin accessibility in Ewing sarcoma	SMART
4:25-4:45	Adriana Ruby Gaona 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.	Evaluating the Association Between Prenatal Toxic Metal Exposure and Placental DNA Methylation	SMART
4:50-5:10	Chavely Gonzalez Ramirez 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.	“TCF4 expression in the developing Macaque neocortex.”	SMART

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