Genetics and Genomics Commons^™

The Role Of B Cell Activation State And Sex In Aryl Hydrocarbon Receptor Mediated Induction Of Chemokine Receptor 9 And Alpha4beta7 Expression In Vitro, Logan Bauerle

Master's Theses

Defense of mucosal tissues from microbial infection and allergy is reliant on continual production of antibodies. The aryl hydrocarbon receptor (AhR) is known to regulate B cell development and is associated with suppression of systemic humoral immunity. Recent attention has been paid to the role of the AhR in altering expression of cell adhesion molecules (CAMs). B cells express CAMs and chemokine receptors to migrate around the body for localized secretion of antibodies. AhR agonists promote B cell migration to the small intestine through upregulation of chemokine receptor 9 (CCR9) and integrin α₄β₇. Both the AhR …

Mismatch Repair Deficient Neoantigen And Associated Circulating T-Cell Receptor Repertoires In Lynch Syndrome, Ana Bolivar

Dissertations and Theses (Open Access)

Lynch Syndrome (LS) is the most common inherited colorectal cancer (CRC) syndrome. It constitutes the perfect model to understand DNA mismatch repair deficient (MMRd) carcinogenesis, which underlies 15% of early-stage CRC. LS patients develop MMRd tumors with high loads of shared neoantigens (neoAgs), which are recognized by the immune system. Previous research has concentrated on discovering neoAgs and their potential as targets for vaccines in LS patients. However, these studies have primarily identified shared neoAgs from cancers, lacking detailed information on targetable neoAgs present in precancerous lesions. Understanding this landscape of pre-cancer derived neoAgs is crucial for intercepting cancer development …

Uncovering Capillary Endothelial Cells Response During Lung Injury-Repair, Celine Shuet Lin Kong

Dissertations and Theses (Open Access)

Once thought to be a homogenous population, capillary endothelial cells (ECs) have embodied organotypic specialization and heterogenous properties, both during homeostasis and tissue injury. In the lung, capillary ECs consist of two distinct populations, CAP1 and CAP2s; how each population responds to diverse tissue injury is incompletely understood. In this thesis, I report the induction and function of a truncated isoform of Ntrk2, Ntrk2^-tk (lacking the tyrosine kinase domain) in multiple injury models. Using a combinatorial approach of single-cell multiome, mouse genetics and viral infection models, I found that Ntrk2^-tk is broadly induced in CAP1s after the initial …

Acute Pain Prediction In Oral Cavity And Oropharyngeal Cancer Patients Receiving Radiation Therapy, Vivian Salama

Dissertations and Theses (Open Access)

Oral-Cavity and oropharyngeal cancers (OC/OPC) are types of head and neck cancers that are increasing in incidence domestically. Radiation therapy (RT) is crucial in OC/OPC management. Pain is a common and challenging symptom for most patients during therapy, as nearly all patients undergoing locoregional RT in OC/OPC require analgesia for acute iatrogenic pain. Moreover, about 45% of long-term survivors report chronic pain, with more than 10% exhibiting severe chronic pain. Pain control is challenging due to the multifactorial clinical, molecular, and cellular etiology of cancer/therapy pain, as well as variation in pain assessment and the non-uniform management of pain between …

Inclusion Of Adoption As A Pregnancy Management Option In Prenatal Genetic Counseling Practice, Emma Billings

Dissertations and Theses (Open Access)

Prenatal genetic counselors are essential to providing education, psychosocial support, and guidance on pregnancy options to patients who receive a fetal diagnosis of an anomaly or genetic condition. Therefore, genetic counselors should be well-educated on comprehensive pregnancy management options consisting of parenting, abortion, and adoption. The landscape of adoption education in genetic counseling practice was last characterized in 2010 by Perry and Henry, revealing substantial variability in both the inclusion of adoption-specific education in genetic counseling program (GCP) curricula and the discussion of pregnancy options with patients in prenatal practice. As a result, the authors published a call to action …

Case Of Human Orthohantavirus Infection, Michigan, Usa, 2021, Samuel M Goodfellow, Robert A Nofchissey, Dustin Arsnoe, Chunyan Ye, Seonghyeon Lee, Jieun Park, Won-Keun Kim, Kartik Chandran, Shannon L M Whitmer, John D Klena, Jonathan W Dyal, Trevor Shoemaker, Diana Riner, Mary Grace Stobierski, Kimberly Signs, Steven B Bradfute

Faculty, Staff and Student Publications

Orthohantaviruses cause hantavirus cardiopulmonary syndrome; most cases occur in the southwest region of the United States. We discuss a clinical case of orthohantavirus infection in a 65-year-old woman in Michigan and the phylogeographic link of partial viral fragments from the patient and rodents captured near the presumed site of infection.

Cranio-Cervical Abnormalities In Moderate-To-Severe Osteogenesis Imperfecta – Genotypic And Phenotypic Determinants, Juliana Marulanda, Jean-Marc Retrouvey, Brendan Lee, V Reid Sutton, Frank Rauch, Michelle Briner

Faculty, Staff and Students Publications

INTRODUCTION: Cranio-cervical anomalies are significant complications of osteogenesis imperfecta (OI), a rare bone fragility disorder that is usually caused by mutations in collagen type I encoding genes.

OBJECTIVE: To assess cranio-cervical anomalies and associated clinical findings in patients with moderate-to-severe OI using 3D cone beam computed tomography (CBCT) scans.

METHODS: Cross-sectional analysis of CBCT scans in 52 individuals with OI (age 10-37 years; 32 females) and 40 healthy controls (age 10-32 years; 26 females). Individuals with a diagnosis of OI type III (severe, n = 11), type IV (moderate, n = 33) and non-collagen OI (n = 8) were recruited …

In Silico Analysis Of C-Type Lectins As Co-Infection Receptors Of Dengue And Chikungunya Viruses In Aedes Aegypti, Munawir Sazali, R. C. Hidayat Soesilohadi, Nastiti Wijayanti, Tri Wibawa, Arif Nur Muhammad Ansori

Makara Journal of Science

Aedes aegypti is a primer vector of dengue virus (DENV) and chikungunya virus (CHIKV). The susceptibility of mosquitoes to DENV and CHIKV depends on their recognition receptor of pathogens. C-type lectins (CTLs) are an important mediator of virus infection in A. aegypti. This study aims to identify potential receptors and determine the binding affinity between ligand–receptor interaction, CTLs and virus envelopes (DENV-1, 2, 3, and 4 and CHIKV) interaction based on in silico analysis. Sample sequences were obtained from GenBank (NCBI), and 10 CTLs were acquired from VectorBase. Homology modeling based on a minimum standard of 20% was processed …

Advancing Primary Ciliary Dyskinesia Diagnosis Through High-Speed Video Microscopy Analysis, Wilfredo De Jesús-Rojas, Zachary J Demetriou, José Muñiz-Hernández, Gabriel Rosario-Ortiz, Frances M Quiñones, Marcos J Ramos-Benitez, Ricardo A Mosquera

Faculty, Staff and Student Publications

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite 70% of Puerto Rican patients having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency …

Genetic Drivers Of Heterogeneity In Type 2 Diabetes Pathophysiology, Ken Suzuki, Konstantinos Hatzikotoulas, Lorraine Southam, Henry J Taylor, Xianyong Yin, Kim M Lorenz, Ravi Mandla, Alicia Huerta-Chagoya, Giorgio E M Melloni, Stavroula Kanoni, Nigel W Rayner, Ozvan Bocher, Ana Luiza Arruda, Kyuto Sonehara, Shinichi Namba, Simon S K Lee, Michael H Preuss, Lauren E Petty, Philip Schroeder, Brett Vanderwerff, Mart Kals, Fiona Bragg, Kuang Lin, Xiuqing Guo, Weihua Zhang, Jie Yao, Young Jin Kim, Mariaelisa Graff, Fumihiko Takeuchi, Jana Nano, Amel Lamri, Masahiro Nakatochi, Sanghoon Moon, Robert A Scott, James P Cook, Jung-Jin Lee, Ian Pan, Daniel Taliun, Esteban J Parra, Jin-Fang Chai, Lawrence F Bielak, Yasuharu Tabara, Yang Hai, Gudmar Thorleifsson, Niels Grarup, Tamar Sofer, Matthias Wuttke, Chloé Sarnowski, Christian Gieger, Darryl Nousome, Stella Trompet, Soo-Heon Kwak, Jirong Long, Meng Sun, Lin Tong, Wei-Min Chen, Suraj S Nongmaithem, Raymond Noordam, Victor J Y Lim, Claudia H T Tam, Yoonjung Yoonie Joo, Chien-Hsiun Chen, Laura M Raffield, Bram Peter Prins, Aude Nicolas, Lisa R Yanek, Guanjie Chen, Jennifer A Brody, Edmond Kabagambe, Ping An, Anny H Xiang, Hyeok Sun Choi, Brian E Cade, Jingyi Tan, K Alaine Broadaway, Alice Williamson, Zoha Kamali, Jinrui Cui, Manonanthini Thangam, Linda S Adair, Adebowale Adeyemo, Carlos A Aguilar-Salinas, Tarunveer S Ahluwalia, Sonia S Anand, Alain Bertoni, Jette Bork-Jensen, Ivan Brandslund, Thomas A Buchanan, Charles F Burant, Adam S Butterworth, Mickaël Canouil, Juliana C N Chan, Li-Ching Chang, Miao-Li Chee, Ji Chen, Shyh-Huei Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Mary Cushman, John Danesh, Swapan K Das, H Janaka De Silva, George Dedoussis, Latchezar Dimitrov, Ayo P Doumatey, Shufa Du, Qing Duan, Kai-Uwe Eckardt, Leslie S Emery, Daniel S Evans, Michele K Evans, Krista Fischer, James S Floyd, Ian Ford, Oscar H Franco, Timothy M Frayling, Barry I Freedman, Pauline Genter, Hertzel C Gerstein, Vilmantas Giedraitis, Clicerio González-Villalpando, Maria Elena González-Villalpando, Penny Gordon-Larsen, Myron Gross, Lindsay A Guare, Sophie Hackinger, Liisa Hakaste, Sohee Han, Andrew T Hattersley, Christian Herder, Momoko Horikoshi, Annie-Green Howard, Willa Hsueh, Mengna Huang, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Mohammad Arfan Ikram, Martin Ingelsson, Md Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Guozhi Jiang, Jost B Jonas, Torben Jørgensen, Frederick K Kamanu, Fouad R Kandeel, Anuradhani Kasturiratne, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M Keaton, Abel N Kho, Chiea-Chuen Khor, Muhammad G Kibriya, Duk-Hwan Kim, Florian Kronenberg, Johanna Kuusisto, Kristi Läll, Leslie A Lange, Kyung Min Lee, Myung-Shik Lee, Nanette R Lee, Aaron Leong, Liming Li, Yun Li, Ruifang Li-Gao, Symen Ligthart, Cecilia M Lindgren, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Adam E Locke, Tin Louie, Jian'an Luan, Andrea O Luk, Xi Luo, Jun Lv, Julie A Lynch, Valeriya Lyssenko, Shiro Maeda, Vasiliki Mamakou, Sohail Rafik Mansuri, Koichi Matsuda, Thomas Meitinger, Olle Melander, Andres Metspalu, Huan Mo, Andrew D Morris, Filipe A Moura, Jerry L Nadler, Michael A Nalls, Uma Nayak, Ioanna Ntalla, Yukinori Okada, Lorena Orozco, Sanjay R Patel, Snehal Patil, Pei Pei, Mark A Pereira, Annette Peters, Fraser J Pirie, Hannah G Polikowsky, Bianca Porneala, Gauri Prasad, Laura J Rasmussen-Torvik, Alexander P Reiner, Michael Roden, Rebecca Rohde, Katheryn Roll, Charumathi Sabanayagam, Kevin Sandow, Alagu Sankareswaran, Naveed Sattar, Sebastian Schönherr, Mohammad Shahriar, Botong Shen, Jinxiu Shi, Dong Mun Shin, Nobuhiro Shojima, Jennifer A Smith, Wing Yee So, Alena Stančáková, Valgerdur Steinthorsdottir, Adrienne M Stilp, Konstantin Strauch, Kent D Taylor, Barbara Thorand, Unnur Thorsteinsdottir, Brian Tomlinson, Tam C Tran, Fuu-Jen Tsai, Jaakko Tuomilehto, Teresa Tusie-Luna, Miriam S Udler, Adan Valladares-Salgado, Rob M Van Dam, Jan B Van Klinken, Rohit Varma, Niels Wacher-Rodarte, Eleanor Wheeler, Ananda R Wickremasinghe, Ko Willems Van Dijk, Daniel R Witte, Chittaranjan S Yajnik, Ken Yamamoto, Kenichi Yamamoto, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Salim Yusuf, Matthew Zawistowski, Liang Zhang, Wei Zheng, Leslie J Raffel, Michiya Igase, Eli Ipp, Susan Redline, Yoon Shin Cho, Lars Lind, Michael A Province, Myriam Fornage, Craig L Hanis, Erik Ingelsson, Alan B Zonderman, Bruce M Psaty, Ya-Xing Wang, Charles N Rotimi, Diane M Becker, Fumihiko Matsuda, Yongmei Liu, Mitsuhiro Yokota, Sharon L R Kardia, Patricia A Peyser, James S Pankow, James C Engert, Amélie Bonnefond, Philippe Froguel, James G Wilson, Wayne H H Sheu, Jer-Yuarn Wu, M Geoffrey Hayes, Ronald C W Ma, Tien-Yin Wong, Dennis O Mook-Kanamori, Tiinamaija Tuomi, Giriraj R Chandak, Francis S Collins, Dwaipayan Bharadwaj, Guillaume Paré, Michèle M Sale, Habibul Ahsan, Ayesha A Motala, Xiao-Ou Shu, Kyong-Soo Park, J Wouter Jukema, Miguel Cruz, Yii-Der Ida Chen, Stephen S Rich, Roberta Mckean-Cowdin, Harald Grallert, Ching-Yu Cheng, Mohsen Ghanbari, E-Shyong Tai, Josee Dupuis, Norihiro Kato, Markku Laakso, Anna Köttgen, Woon-Puay Koh, Donald W Bowden, Colin N A Palmer, Jaspal S Kooner, Charles Kooperberg, Simin Liu, Kari E North, Danish Saleheen, Torben Hansen, Oluf Pedersen, Nicholas J Wareham, Juyoung Lee, Bong-Jo Kim, Iona Y Millwood, Robin G Walters, Kari Stefansson, Emma Ahlqvist, Mark O Goodarzi, Karen L Mohlke, Claudia Langenberg, Christopher A Haiman, Ruth J F Loos, Jose C Florez, Daniel J Rader, Marylyn D Ritchie, Sebastian Zöllner, Reedik Mägi, Nicholas A Marston, Christian T Ruff, David A Van Heel, Sarah Finer, Joshua C Denny, Toshimasa Yamauchi, Takashi Kadowaki, John C Chambers, Maggie C Y Ng, Xueling Sim, Jennifer E Below, Philip S Tsao, Kyong-Mi Chang, Mark I Mccarthy, James B Meigs, Anubha Mahajan, Cassandra N Spracklen, Josep M Mercader, Michael Boehnke, Jerome I Rotter, Marijana Vujkovic, Benjamin F Voight, Andrew P Morris, Eleftheria Zeggini

Faculty, Staff and Student Publications

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

Bi-Allelic Variants In Celsr3 Are Implicated In Central Nervous System And Urinary Tract Anomalies, Jil D Stegmann, Jeshurun C Kalanithy, Gabriel C Dworschak, Nina Ishorst, Enrico Mingardo, Filipa M Lopes, Yee Mang Ho, Phillip Grote, Tobias T Lindenberg, Öznur Yilmaz, Khadija Channab, Steve Seltzsam, Shirlee Shril, Friedhelm Hildebrandt, Felix Boschann, André Heinen, Angad Jolly, Katherine Myers, Kim Mcbride, Mir Reza Bekheirnia, Nasim Bekheirnia, Marcello Scala, Manuela Morleo, Vincenzo Nigro, Annalaura Torella, Tudp Consortium, Michele Pinelli, Valeria Capra, Andrea Accogli, Silvia Maitz, Alice Spano, Rory J Olson, Eric W Klee, Brendan C Lanpher, Se Song Jang, Jong-Hee Chae, Philipp Steinbauer, Dietmar Rieder, Andreas R Janecke, Julia Vodopiutz, Ida Vogel, Jenny Blechingberg, Jennifer L Cohen, Kacie Riley, Victoria Klee, Laurence E Walsh, Matthias Begemann, Miriam Elbracht, Thomas Eggermann, Arzu Stoppe, Kyra Stuurman, Marjon Van Slegtenhorst, Tahsin Stefan Barakat, Maureen S Mulhern, Tristan T Sands, Cheryl Cytrynbaum, Rosanna Weksberg, Federica Isidori, Tommaso Pippucci, Giulia Severi, Francesca Montanari, Michael C Kruer, Somayeh Bakhtiari, Hossein Darvish, Heiko Reutter, Gregor Hagelueken, Matthias Geyer, Adrian S Woolf, Jennifer E Posey, James R Lupski, Benjamin Odermatt, Alina C Hilger

Faculty, Staff and Students Publications

CELSR3 codes for a planar cell polarity protein. We describe twelve affected individuals from eleven independent families with bi-allelic variants in CELSR3. Affected individuals presented with an overlapping phenotypic spectrum comprising central nervous system (CNS) anomalies (7/12), combined CNS anomalies and congenital anomalies of the kidneys and urinary tract (CAKUT) (3/12) and CAKUT only (2/12). Computational simulation of the 3D protein structure suggests the position of the identified variants to be implicated in penetrance and phenotype expression. CELSR3 immunolocalization in human embryonic urinary tract and transient suppression and rescue experiments of Celsr3 in fluorescent zebrafish reporter lines further support an …

Unraveling The Genetic Architecture Of Congenital Vertebral Malformation With Reference To The Developing Spine, Sen Zhao, Hengqiang Zhao, Lina Zhao, Xi Cheng, Zhifa Zheng, Mengfan Wu, Wen Wen, Shengru Wang, Zixiang Zhou, Haibo Xie, Dengfeng Ruan, Qing Li, Xinquan Liu, Chengzhu Ou, Guozhuang Li, Zhengye Zhao, Guilin Chen, Yuchen Niu, Xiangjie Yin, Yuhong Hu, Xiaochen Zhang, Deciphering Disorders Involving Scoliosis And Comorbidities (Disco) Study, Pengfei Liu, Guixing Qiu, Wanlu Liu, Chengtian Zhao, Zhihong Wu, Jianguo Zhang, Nan Wu

Faculty, Staff and Students Publications

Congenital vertebral malformation, affecting 0.13-0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord …

Nonchromosomal Birth Defects And Risk Of Childhood Acute Leukemia: An Assessment In 15 000 Leukemia Cases And 46 000 Controls From The Childhood Cancer And Leukemia International Consortium, Philip J Lupo, Tiffany M Chambers, Beth A Mueller, Jacqueline Clavel, John D Dockerty, David R Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E Heck, Claire Infante-Rivard, Alice Y Kang, Corrado Magnani, Carlotta Malagoli, Erin L Marcotte, Catherine Metayer, Helen D Bailey, Ana M Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S Pombo-De-Oliveira, Wafaa M Rashed, Eve Roman, Joachim Schüz, Catharina Wesseling, Logan G Spector, Michael E Scheurer

Faculty, Staff and Students Publications

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia …

Association Between Regulatory T Cells And Ischemic Heart Disease: A Mendelian Randomization Study, Yucheng Hou, Ke Si, Jingyue Yang, Tan Liu, Basel Abdelazeem, Nonthikorn Theerasuwipakorn, Jingwei Zhao, Zhenya Shen

Faculty, Staff and Student Publications

BACKGROUND: An imbalance of innate and acquired immune responses is significantly involved in the pathophysiology of coronary atherosclerosis and the occurrence of ischemic heart disease (IHD). Regulatory T cells (Tregs) play an essential regulatory role in atherosclerotic plaque formation and maintenance; therefore, dysfunction of Tregs triggers the formation of atherosclerotic plaques and accelerates their progression. However, due to the inherent limitations of observational research, clinical evidence is limited concerning the relationship between the variation in peripheral Tregs and the risk of IHD, and the cause-and-effect relationship between these factors is unclear. Mendelian randomization (MR) uses genetic variation as a proxy …

Novel Pan-Err Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism And Mitochondrial Function, Weiyi Xu, Cyrielle Billon, Hui Li, Andrea Wilderman, Lei Qi, Andrea Graves, Jernie Rae Dela Cruz Rideb, Yuanbiao Zhao, Matthew Hayes, Keyang Yu, Mckenna Losby, Carissa S Hampton, Christiana M Adeyemi, Seok Jae Hong, Eleni Nasiotis, Chen Fu, Tae Gyu Oh, Weiwei Fan, Michael Downes, Ryan D Welch, Ronald M Evans, Aleksandar Milosavljevic, John K Walker, Brian C Jensen, Liming Pei, Thomas Burris, Lilei Zhang

Faculty, Staff and Students Publications

BACKGROUND: Cardiac metabolic dysfunction is a hallmark of heart failure (HF). Estrogen-related receptors ERRα and ERRγ are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential therapeutic intervention for HF. However, in vivo studies demonstrating the potential usefulness of ERR agonist for HF treatment are lacking, because compounds with pharmacokinetics appropriate for in vivo use have not been available.

METHODS: Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915. We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo. We …

Contextualizing The Revised Patient Perception Of Patient-Centeredness (Pppc-R) Scale In Primary Healthcare Settings: A Validity And Reliability Evaluation Study, Yiyuan Cai, Pengfei Guo, Jiong Tu, Mengyao Hu, Lingrui Liu, Bridget L Ryan, Jing Liao, Rubee Dev, Yiran Li, Tianyu Huang, Ruilin Wang, Li Kuang, Ruonan Huang, Xinfang Li, Edmundo Roberto Melipillán, Shuaixiang Zhao, Wenjun He, Xiaohui Wang, Nan Zhang, Dong Roman Xu

Faculty, Staff and Student Publications

BACKGROUND: An English version of the Patient Perception of Patient-Centeredness (PPPC) scale was recently revised, and it is necessary to test this instrument in different primary care populations.

AIM: This study aimed to assess the validity and reliability of a Chinese version of the PPPC scale.

DESIGN: A mixed method was used in this study. The Delphi method was used to collect qualitative and quantitative data to address the content validity of the PPPC scale by calculating the Content Validity Index, Content Validity Ratio, the adjusted Kappa, and the Item Impact Score. Confirmatory factor analysis (CFA) and exploratory factor analysis …

The Use Of Cardiac Magnetic Resonance In Hypertrophic Cardiomyopathy Over The Past 10 Years [2013-2023]: A Citespace-Based Bibliometric Analysis, Mengyao Hu, Yu Shen, Yipei Song, Shuhao Li, Pei Yang, Ao Kan, Qiming Fang, Yun Peng, Haibo Ren, Yajing Zhang, Lianggeng Gong

Faculty, Staff and Student Publications

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common genetic cardiac disorder characterized by the hypertrophy of a segment of the myocardium. Cardiac magnetic resonance (CMR) has been widely used in the assessment of HCM. However, no bibliometric assessment has been conducted on the progress of research in this field. This study thus aimed to examine the current state of research into the application of CMR in HCM and the hotspots and trends that have emerged in this field over the past decade.

METHODS: A systematic search was conducted on the Web of Science regarding CMR in the assessment of HCM. The …

Fused In Sarcoma Regulates Glutamate Signaling And Oxidative Stress Response, Chiong-Hee Wong, Abu Rahat, Howard C Chang

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Mutations in fused in sarcoma (fust-1) are linked to ALS. However, how these ALS causative mutations alter physiological processes and lead to the onset of ALS remains largely unknown. By obtaining humanized fust-1 ALS mutations via CRISPR-CAS9, we generated a C. elegans ALS model. Homozygous fust-1 ALS mutant and fust-1 deletion animals are viable in C. elegans. This allows us to better characterize the molecular mechanisms of fust-1-dependent responses. We found FUST-1 plays a role in regulating superoxide dismutase, glutamate signaling, and oxidative stress. FUST-1 suppresses SOD-1 and VGLUT/EAT-4 in the nervous system. FUST-1 also regulates synaptic AMPA-type glutamate receptor …

Managing Stress: A Study Of Stress Response Mechanisms In Mycobacteria, Augusto C. Hunt Serracin

Biology Dissertations - Archive

Mycobacteria encompass many pathogenic species known to cause severe disease in humans. A well-known example is Mycobacterium tuberculosis (Mtb), the causative agent of the lung disease tuberculosis, which kills millions of humans worldwide yearly. Pathogenic mycobacteria like Mtb are challenging to treat because of their innate ability to adapt to environmental stress. Their unique cell physiology and conserved stress responses allow them to combat biological insults, regulate growth, and regulate genes involved in stress; all these responses increase tolerance to antibiotics. The current therapies to treat mycobacterial infections are lengthy and, at times, unsuccessful, partly due to antibiotic tolerance. A …

Exploration Of Potential Broad-Spectrum Antiviral Targets In The Enterovirus Replication Element: Identification Of Six Distinct 5' Cloverleaves, Morgan G. Daniels, Meagan E. Werner, Rockwell T. Li, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

Enterovirus genomic replication initiates at a predicted RNA cloverleaf (5′CL) at the 5′ end of the RNA genome. The 5′CL contains one stem (SA) and three stem-loops (SLB, SLC, SLD). Here, we present an analysis of 5′CL conservation and divergence for 209 human health-related serotypes from the enterovirus genus, including enterovirus and rhinovirus species. Phylogenetic analysis indicates six distinct 5′CL serotypes that only partially correlate with the species definition. Additional findings include that 5′CL sequence conservation is higher between the EV species than between the RV species, the 5′CL of EVA and EVB are nearly identical, and RVC has the …

The Splice Index As A Prognostic Biomarker Of Strength And Function In Myotonic Dystrophy Type 1, Marina Provenzano

Theses and Dissertations

Myotonic dystrophy type 1 (DM1) is a slowly progressive, multisystem disorder caused by a CTG repeat expansion in the DMPK 3’UTR that leads to global dysregulation of alternative splicing. The resulting decline in physical function is slow, and no reliable biomarkers exist for predicting disease progression; however, an RNA mis-splicing biomarker associated with weakness may have utility in predicting functional outcomes. Here we validate the Splice Index (SI) as a potential biomarker of DM1-associated strength and function. Muscle biopsies of the tibialis anterior were collected from DM1-affected individuals at baseline (n = 46) and 3-months (n = 34), along with …

The Influence Of Drd2 Polymorphism Exon 8 C/T (Rs6276) On Manifestations Of Delirium Tremens & Alcohol Withdrawal Seizures, Naomi Schneider

Honors Theses and Capstones

This study explores the correlation between the DRD2 Polymorphism exon 8 C/T (rs6276) and manifestations of delirium tremens (DT). DT is a condition that is clinically diagnosed utilizing two characteristic symptom manifestations: the presence of delirium and severe alcohol withdrawal. It is not entirely understood why DT can occur in some patients, but evidence has suggested that genetic predisposition can play a role. Utilizing the National Institutes of Health (NIH) All of Us Research database and performing a secondary analysis of existing genomic data, this candidate gene association study aims to determine the genotype frequencies within three cohorts: a healthy …

Contributions Of The Replication Initiator Protein Dnaa To Physiology And Virulence Of The Lyme Disease Spirochete, Andrew Krusenstjerna

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Borrelia burgdorferi, the etiological agent of Lyme disease, is the most prevalent vector-borne disease in the United States. The spirochetal population is naturally maintained by consistently cycling between Ixodid ticks and small vertebrates. To survive within these diverse niches, B. burgdorferi has evolved a unique physiology and regulatory network to sense and respond to environmental fluxes. Replication is a hallmark of the Lyme spirochete’s enzootic life cycle, specifically at the nymphal tick-to-vertebrate interface. The mechanisms and regulatory schema for the basic cellular processes in B. burgdorferi, or indeed any member of the phylum spirochaetota, are largely unknown. The central hypothesis …

Role Of Human Intermediate Form Prl Receptor I-Tail In The Pathogenesis Of Breast Cancer, Shanwei Shen

Theses and Dissertations

Breast cancer continues to be the second most common cancer in women in the United States. The neuroendocrine hormone human prolactin (hPRL) plays an important role in normal mammary gland development and growth, stimulating normal breast tissue proliferation and differentiation. Considerable evidence has shown that hPRL is involved in the malignant transformation of human breast tissue. hPRL enhances viability, invasiveness, and proliferation of breast cancer cells in vitro. Evidence from epidemiologic and genetic studies also implicates role of hPRL in the pathogenesis of breast cancer. Its cognate receptor the human prolactin receptor (hPRLr) is required for the action of hPRL. …

Alopecia As An Early Clinical Marker For Azathioprine Induced Myelosuppression: A Case Report, Nilanjana Dutta , Final Year Mbbs, Dr. M Suresh Babu , Professor, Dr. Subramanian Ramaswamy , Professor, Dr. Mahabaleshwar Mamadapur , Assistant Professor

Digital Journal of Clinical Medicine

Azathioprine is a pro-drug and is metabolized by the TPMT enzyme in the body. In South Asians, Azathioprine is known to cause alopecia and bone marrow suppression in patients with TPMT enzyme deficiency. In India, the prevalence of TPMT mutation varies from 1.2- 10%. A new mutation was detected in 2014, NUDT15 whose incidence varies from 8.5-16%. Patients with mutation in both TPMT and NUDT15 develop myelosuppression faster. In our case, alopecia manifested as the first clinical feature of Azathioprine myelosuppression. Physicians need to recognize early clinical clues (alopecia) to avoid the impending development of myelosuppression and to look for …

Examining Potential Causal Associations Of Sedentary Time And Physical Activity With Heart Failure Using Subjective And Objective Measures: A Mendelian Randomization Analysis, Jessica Geller

UNF Graduate Theses and Dissertations

Purpose: The objective of this study was to assess the causal relationship between both subjectively and objectively measured sedentary time (ST) and physical activity (PA) with heart failure (HF) risk, utilizing Mendelian Randomization (MR) approach.

Methods: The present MR used genetic instruments identified for self-reported ST and PA extracted from 51 genome wide association studies (GWAS), encompassing data from 703,901 individuals. The GWAS identified 89 independent single nucleotide polymorphisms (SNPs) associated with leisure screen time. Eleven loci were reported to be associated with moderate to vigorous physical activity (MVPA). From another GWAS examining accelerometer-based activities, three loci were found to …

Ribosome Hibernation Factor Induces Antibiotic Persisters Of Mycobacterium Tuberculosis In Neutrophil-Rich Lung Lesions, Jamie Corro

Electronic Theses & Dissertations (2024 - present)

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is a prescient global health threat and the leading cause of death by an infectious agent. Treatment of Mtb infection involves administering 2-4 antibiotics for a minimum of 6 months. This extended drug regimen is required to target a subpopulation of persistent bacilli. As their name implies, these bacteria can “persist” by acquiring nonhereditary and transient antibiotic tolerance. Although the precise mechanism is unknown, it’s often attributed to slowing cellular growth and metabolic processes. During zinc deprivation, bacteria can remodel their ribosomes by replacing their zinc-binding paralogues containing the CXXC motif (C+) …

Prevalence Of Congenital Anomalies According To Maternal Race And Ethnicity, Texas, 1999–2018, Jeremy M Schraw, Elwin Jaime, Charles J Shumate, Mark A Canfield, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Few studies of congenital anomalies provide prevalence estimates stratified by maternal race/ethnicity. We sought to determine whether the prevalence of a broad spectrum of anomalies varies among offspring of women from different race/ethnic groups.

METHODS: We obtained information on cases with anomalies from the population-based Texas Birth Defects Registry, and denominator data on livebirths among Texas residents during 1999-2018 from the Texas Center for Health Statistics. We estimated the prevalence ratio (PR) and 95% confidence interval (CI) of N = 145 anomalies among offspring of Hispanic and non-Hispanic Black relative to non-Hispanic White women using Poisson regression, adjusting for …

Parkinson's Disease And Other Alzheimer's Disease And Related Dementia Pathologies And The Progression Of Parkinsonism In Older Adults, Aron S Buchman, Lei Yu, Shahram Oveisgharan, Andrea R Zammit, Tianhao Wang, Joshua M Shulman, Veronique Vanderhorst, Sukrit Nag, David A Bennett

Faculty, Staff and Students Publications

BACKGROUND: The interrelationship of parkinsonism, Parkinson's disease (PD) and other Alzheimer's disease (AD) and Alzheimer's disease and related dementias (ADRD) pathologies is unclear.

OBJECTIVE: We examined the progression of parkinsonian signs in adults with and without parkinsonism, and their underlying brain pathologies.

METHODS: Annual parkinsonian signs were based on a modified Unified Parkinson's Disease Rating Scale. We used linear mixed effects models to compare the progression of parkinsonian signs in 3 groups categorized based on all available clinical evaluations: Group1 (never parkinsonism or clinical PD), Group2 (ever parkinsonism, but never clinical PD), Group3 (ever clinical PD). In decedents, we examined …

A Timeline Of Klinefelter’S Syndrome, Xxy, Emma Chevalier, Tyler Venegas, Mary Salibi

Undergraduate Research Symposium Posters

Klinefelter Syndrome (KS) is a non-mendelian chromosomal disorder consisting of supernumerary X chromosomes in males, 80% of which manifest as the 47,XXY karyotype. The resulting gene dosage abnormalities affect both cognitive and physical development, with variable expressivity. The disease was first described by Harry Klinefelter in 1942 and was thought to be an endocrine disorder until the late 1950s, when karyotyping of affected individuals revealed an extra X chromosome.

(It is the most common sex chromosome aneuploidy (1:500 males) and the most common cause of azoospermia. The phenotype for KS is highly contested due to its extremely variable expressivity and …