Medical Genetics Commons^™

Corticobasal Syndrome With Mixed Pathology In The Absence Of Grn Mutation: A Clinico-Pathological Case Of Ftld-Tdp With Coexisting Alzheimer’S And Lewy Body Pathology, Hugo Zamarron, David Irwin, Jeffery Phillips, Edward Lee, Matthew Tisdall, Corey Mcmillan

Research Colloquium

Background: Corticobasal syndrome (CBS) is a neurodegenerative disorder characterized by often asymmetric fronto-pariteal and extra-pyramidal features that is traditionally associated with tauopathy, but pathological findings are heterogenous, including other forms of frontotemporal lobar degeneration (FTLD) and mixed pathologies of aging. We present clinical, radiographic, and histopathologic features of asymmetry in a unique patient with CBS and underlying FTLD with TDP-43 pathology (FTLD-TDP), co-occurring with other age-related pathologies.

Case Presentation: A 76-year-old man presented with progressive cognitive and motor dysfunction including asymmetric parkinsonism, left-sided dystonia and rigidity, apraxia, visuospatial impairment, and a subtle social disorder including apathy and social withdrawal. The …

The Role Of Ceramides As Biomarkers And Therapeutic Targets For Cardiometabolic Disease And Its Intersection With Cellular Aging, Youssef Moustafa Shalaby

Thesis/ Dissertation Defenses

Ceramides (Cer), a subclass of sphingolipids with potent bioactive properties, have gained recognition as key players in the pathogenesis of cardiometabolic diseases (CMD). They modulate critical cellular functions such as apoptosis, inflammation, insulin signaling, and oxidative stress. This dissertation explores the dual role of Cer as both early diagnostic markers and therapeutic targets, bridging clinical insights with mechanistic understanding through a combination of human and experimental studies.

A highly sensitive liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed and validated to quantify intracellular levels of specific Cer species, including CerC16:0, CerC18:0, CerC22:0, CerC24:0, and CerC24:1. This method was translated into …

Detection Of Chromosomal Mosaicism- The Importance Of Karyotyping And Fish, Allison Kalinousky, Jennifer L. Roberts, Madeeha Alikhan, John Herriges, Lei Zhang, Elena Repnikova

Research Days

This project evaluates the prevalence of chromosomal mosaicism in constitutional samples using conventional cytogenetic techniques evaluated at Children's Mercy Hospital during a 20-year period.

The Correlation Between A Methylenetetrahydrofolate Reductase Deficiency In Autism Spectrum Disorder Patients And The Presence Of Mental Health Disorders, Hinal Joshi, Andrea Iannuzzelli

Rowan-Virtua Research Day

• Currently little literature exists on connection between Methylenetetrahydrofolate reductase (MTHFR) deficiency and mental health disorders

• Reduced enzyme activity associated with certain MTHFR variants contributes to altered folate metabolism, elevated homocysteine levels, and disrupted DNA methylation, all of which are implicated in mental health disorders

• Identifying genetic risk factors could facilitate earlier diagnosis and intervention, leading to improved outcomes

• Relevant results could help reduce stigma and promote greater understanding of challenges faced by patients on the spectrum

Heart To Heart: Exploring Why Cardiovascular Risk Is Higher In South Asians, Jasjeet Kaur Dhaliwal

Rowan-Virtua Research Day

Cardiovascular disease (CVD) is a leading global cause of mortality, but South Asians experience a disproportionately high burden of disease, often developing CVD at younger ages and with lower body mass indices compared to other populations. This project explores the underlying genetic and lifestyle factors contributing to elevated cardiovascular risk in South Asians, aiming to highlight the need for targeted prevention strategies and policy reforms.

A literature review was conducted using peer-reviewed studies, meta-analyses, and reviews published between 2007 and 2024. After screening 47 initial articles, 18 were selected for analysis based on their relevance to genetic and lifestyle risk …

The Cellular Trafficking And Targeting Of Angiotensin-Converting-Enzyme-2 (Ace2) And Neutral-Amino-Acid-Transporter (B0at1) Variants: Implications For The Pathogenesis Of Associated Diseases And Therapy, Nesreen Fayyad Al-Khofash

Thesis/ Dissertation Defenses

Angiotensin-converting enzyme 2 (ACE2) and the amino acid transporter B0AT1 are essential for blood pressure regulation, amino acid absorption, and viral entry. Their interaction is crucial in both normal physiology and disease, including hypertension, Hartnup disease, and SARS-CoV-2 infection. However, the effects of genetic variants on their biogenesis, trafficking, and function remain poorly understood. This PhD thesis investigates how specific ACE2 and B0AT1 variants influence their subcellular localization and interactions. A multidisciplinary approach, incorporating site-directed mutagenesis, confocal microscopy, Western blotting, and in silico modelling, was used to examine 39 ACE2 variants and 18 B0AT1 mutations. Results showed that wild-type ACE2 …

Elucidating The Pathogenic Mechanisms Of Disease-Causing Variants In The Low-Density Lipoprotein Receptor (Ldlr) And The Very-Low-Density Lipoprotein Receptor (Vldlr), Aseel Adnan Jawabri

Thesis/ Dissertation Defenses

The Low-Density Lipoprotein Receptor (LDLR) and the Very-Low-Density Lipoprotein Receptor (VLDLR) are major members of the LDLR family of proteins, and they have been shown to be responsible for Familial hypercholesterolemia (FH) and Cerebellar ataxia, mental retardation, and dysequilibrium syndrome type 1 (CAMRQ1), respectively. FH is an autosomal dominant disorder characterized by increased LDL-cholesterol levels mainly caused by mutations in LDLR. Clinically, FH is characterized by increased levels of LDL-C, tendon xanthomas, corneal arcus, and premature coronary artery diseases (CAD) such as atherosclerosis, if left untreated. CAMRQ-related disorders are a group of rare, heterogeneous, autosomal recessive conditions characterized by cerebellar …

Alk Drives Neuroblastoma Tumorigenesis Via Upregulation Of Postn And Activation Of Wnt And Stat3 Signaling, Miller Huang, Wanqi Fang, Alvin Farrel, Linwei Li, Tania Porras Corredor, Shahab Asgharzadeh, John Maris, William A. Weiss

Research Symposium

Background: Neuroblastoma (NB) is the most common extracranial solid tumor in children. Two of the earliest known genetic drivers of NB are the oncogene MYCN and receptor tyrosine kinase ALK. While animal models show MYCN and mutationally active ALK F1174L can accelerate NB tumorigenesis, the mechanism of this cooperation is unknown. This study applied a human stem cell-based model to elucidate how ALK cooperates with MYCN to accelerate tumorigenesis of NB.

Methods: Induced pluripotent stem cells (iPSCs) were engineered with doxycycline-inducible MYCN and constitutively active ALKF1174L. These iPSCs were differentiated into trunk neural crest cells (tNCCs) and orthotopically transplanted into …

Evaluation Of Various Methods For Obtaining Dna Samples From Remote Individuals, Alexander Baumann, Elden Jenkins, Jared Carter, Mark Crawford, Jonathon Alden Enlow, Marlena Muszynska, Christopher Spencer Walker, Christina Nelson, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

Roseman Symposium 2025

Investigating Comorbidities And Heritability Of Chronic Intractable Migraine With Reactive Hypoglycemia, Stella Santa Ana, Alexander Baumann, Benjamin Gordon, Alex Schofield, Sophia Delgado, Catherine Yvonne Russell, Jacob Warner, Christina Nelson, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

Poster at 2025 Roseman Research Symposium

Observing The Impacts Of Different Diets On Clinical Outcomes In Patients With Alzheimer's Disease: A Scoping Review, Erjola Toska, Alessandra Ottley, Quinn Jackson, Rachel Fricker, Alexa Carleo, Gabriella Cutrali, Olivia D’Alessio, Raquel Rossman, Samuel Kruchakov, Abraham Edelstein, Lubov Nathanson

HCA-NSU MD Research Day

Observing the Impacts of Different Diets on Clinical Outcomes in patients with Alzheimer's disease: A Scoping Review Authors: Quinn Jackson, OMS-III; Rachel Fricker,OMS-III; Erjola Toska, OMS-III; Alessandra Ottley,OMS-III; Alexa Carleo,OMS-III; Gabriella Cutrali, OMS-III; Olivia D’Alessio, OMS-III; Raquel Rossman, OMS-III; Samuel Kruchakov, OMS-III; Abraham Edelstein,OMS-III; Lubov Nathanson, Ph.D. Program: Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine, Florida Objectives: This study aimed to assess the literature published from 2013 to 2023 on the impact of diet on Alzheimer’s Disease (AD). Background: AD is primarily marked by β-amyloid plaques and neurofibrillary tangles, which impair neuronal synapses, leading to memory …

The Role Of Kctd13 In Androgen Receptor Ubiquitination​, Faith Abraham, Ahmed Chahdi, Phd, Carolina Jorgez, Phd, Abhishek Seth

HCA-NSU MD Research Day

The Role of KCTD13 in Androgen Receptor Ubiquitination Faith Abraham1, Ahmed Chahdi, PhD2, Caroline Jorgez, PhD3, and Abhishek Seth, MD2 1Class of 2024, Dr. Kiran C. Patel College of Osteopathic Medicine, 2Urology, Nemours Children’s Hospital, Orlando, FL 3Urology, Baylor College of Medicine, Houston, TX Objective: This study was conducted to determine the effect of the KCTD13 gene on major protein effectors of common genitourinary (GU) defects. Background: Hypospadias, characterized by the ventral positioning of the urethral opening, occurs in approximately 1 out of 125 live births. Cryptorchidism, or undescended testes (UDT), is the most common GU birth defect, affecting around …

Genomics Insights Into Anti-Platelets Therapy: Unraveling Of Variants And The Implementation Of Clopidogrel-Guided Therapy In The United Arab Emirates, Lubna Qasem Khasawneh

Thesis/ Dissertation Defenses

Anti-platelet therapy is a cornerstone in the management of cardiovascular diseases such as acute coronary syndrome (ACS) and stroke. These medications are essential for reducing the risk of thrombotic events by preventing platelet aggregation. However, variations in cardiovascular pharmacogenes can significantly impact the metabolism, efficacy, and safety of anti-platelet therapies, making personalized medicine increasingly important for optimizing treatment outcomes. Pharmacogenomic testing has emerged as a crucial tool in tailoring anti-platelet therapy, particularly for patients with subtherapeutic responses due to genetic factors. While extensive research has been conducted globally to identify and study the effect of the pharmacogenomic variants that influence …

Investigating The Determinants Of Frailty: The Intersection Of Genetics And Environment In Mexican Americans From South Texas, Natasha Garcia-Rodriguez, Vincent P. Diego, Marcio Almeida, Jacob Galan, Sandra Laston, Joanne E. Curran, Tom Howard, Eron Manusov, John Blangero, Sarah Williams-Blangero

Research Colloquium

Background: The projected worldwide population of people aged 65 and over is anticipated to hit 1.6 billion by 2050. Frailty, marked by increased susceptibility to adverse health outcomes, mortality, and decreased health-related quality of life (HrQoL), poses significant challenges to an aging population. The Frailty Index (FI), is the ratio of the number of accumulated health deficits to the total number of deficits considered, is used to predict frailty.

Methods: Utilizing data from the Mexican American Family Study, we investigated the heritability and gene-environment (GxE) interactions influencing frailty in 1,029 Mexican American participants. We calculated the FI using 34 variables, …

Systemic Biology Approach Linking Type 2 Diabetes And Depression In A Rio Grande Valley Family Study Population, Cameron B. Caldwell, Eron Manusov, Vincent P. Diego, Ana C. Leandro, Sandra Laston, John Blangero, Sarah Williams-Blangero, Marcio Almeida

Research Colloquium

Background: Type 2 diabetes and depression are major public health concerns that disproportionally impact Mexican Americans. Prevalence of T2D and depression have been estimated as high as 30% and 40%, respectively in Mexican American populations along the Texas-Mexico border. While the interaction between these two phenotypes is well documented, the underlying genetic basis of this interaction remains unclear. Our aims for this project were to identify genes co-expressed in type 2 diabetes and depression to dissect the interaction correlations between both conditions by means of a functional gene expression correlation network.

Methods: A total of 528 Mexican American participants from …

Ongoing Study Of The Association Of Apoe Gene Polymorphisms With Cognitive Impairment In The Rio Grande Valley Hispanic Population, Jaime Miguel L. Saveron, Daniela Gamez, Chun Xu

Research Symposium

Background: Alzheimer's disease (AD), a prevalent neurodegenerative disorder, exhibits a significant genetic component. In addition, mild cognitive impairment (MCI) is a key risk factor for AD. While certain demographic factors and genetic variants associated with AD and cognitive impairment have been identified in non-Hispanic populations, limited research exists on this subject within the Hispanic population, particularly in the Rio Grande Valley. This study aims to investigate the relationship between the APOE gene, specifically its ε4 allele, and cognitive impairment in the Hispanic population of the Rio Grande Valley.

Methods: A total of 269 Hispanic subjects, aged 60 and above, with …

Emerging Unconventional Therapies For Glioblastoma Multiforme, Danielle Morang

Capstone Showcase

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary malignant brain tumor occurring in adults with a median survival of less than two years. It is a highly invasive tumor characterized by genetic heterogeneity, angiogenesis, and rapid proliferation. Patients undergo a multimodal treatment regimen consisting of surgical resection and chemoradiation therapy, yet GBM tumors almost always recur with a worsening prognosis. The molecular and genetic complexities of GBM pose a significant challenge for developing effective therapeutics. Thus, it is imperative to identify new therapeutic targets and explore novel treatment strategies to improve patients’ overall survival time and quality of …

Functional Characterization Of The Ipsc Generated Hepatocytes Using Genome-Wide Transcriptomic Analysis, Ashley Ikwuezunma, Erica De Leon, Ana C. Leandro, Joanne E. Curran, John Blangero, Satish Kumar

Research Colloquium

Advances in iPSC technologies now allow us to consider non-invasive large-scale in-vitro disease modeling experiments on disease appropriate cell types in human subjects to better understand human disease pathophysiology, disease genetics and to develop better diagnostic and therapeutic technologies. We performed differential gene expression and functional annotation analysis using genome wide mRNA sequencing data to evaluate the functional and disease modeling potential of iPSC generated hepatocytes. Following the criteria moderated t statistics FDR corrected p-value ≤ 0.05 and fold change-absolute ≥ 2.0, 7,246 genes/transcripts were significantly differentially expressed iPSCs and hepatocytes. The 3,791 of these DE genes/transcripts were significantly …

Gene By Environment Interaction And Metabolic-Associated Fatty Liver Disease In Mexican American Patients With Depression, Khalid Sheikh, Vincent P. Diego, Sandra L. Laston, Eron G. Manusov, Sarah Williams-Blangero, John Blangero

Research Colloquium

Knowledge of genetic and environmental (G x E) interaction effects on metabolic-associated fatty liver disease (MAFLD) is limited. The purpose of this study was to examine the impact of G x E interaction effects on MAFLD in Mexican Americans in the Rio Grande Valley (RGV). The environment examined was depression as measured by the Beck Depression Inventory-II (BDI-II). We examined potential G x E interaction in the phenotypic expression of MAFLD, including hepatic steatosis and hepatic fibrosis, using variance component models and likelihood-based statistical inference. Significant G x E interactions were identified for hepatic fibrosis x BDI-II. These findings provide …

Variant Of Fii Gene Plays A Critical Role In Coagulation Potential In Mexican-Americans, Hoang Anh T. Nguyen, Shuchita Vijay Jhaveri, Marcio A. Almeida, Vincent P. Diego, Satish Kumar, Juan M. Peralta, Joanne E. Curran, Bernadette W. Luu, Donna M. Lehman, Ralph A. Defronzo, Laura Almasy, Sarah Williams-Blangero, Ravi Duggirala, John Blangero, Tom Howard

Research Symposium

Background: Disruption in the balance between coagulation and bleeding can result in varying phenotypes such as hypercoagulability and can lead to the development of cardiovascular disease. In our study utilizing extended families of Mexican-Americans from South Texas, we performed a search for protein-altering variants influencing coagulation potential.

Methods: Mexican-Americans in the study were genotyped using Illumina-(human)-exome-24 chip to screen for protein-altering variants. Variants were analyzed for their association with FII activity, aPTT, and PT. Linear-mixed-model analysis was performed to estimate trait heritabilities and to interrogate single nucleotide variations (SNV) for evidence of genetic association. To control for multiple testing, associations …

Dpyd Pathogenic Variants Associated With Fluoropyrimidines Toxicity, Diana Cristina Pérez-Ibave, Noé Israel Oliva-García, Irasema Ramos-Martínez, Francisco Javier Villarreal Alvarado, Valeria Jimena Gómez Ordaz, Jonatán Isaí Cortes Alfaro, Carlos Horacio Burciaga-Flores, Juan Francisco González-Guerrero, Oscar Vidal-Gutiérrez, Maria De Lourdes Garza-Rodriguez

Research Symposium

Background: Genetic variants in dihydropyrimidine dehydrogenase gene (DPYD) coding for the key enzyme (DPD) of fluoropyrimidines (FPs) catabolism. DPYD contributes to the development of severe FPs-related toxicity, and pathogenic DPYD variants detection reduces side effects and complications associated with FP-toxicity. The allelic frequency of these variants in the Mexican population is currently unknown.

Methods: The study was carried out at the Centro Universitario Contra el Cáncer (CUCC) of the Universidad Autónoma de Nuevo León (UANL) in Monterrey México. Genomic DNA was isolated from 154 subjects using the QIAamp DNA Blood Midi kit (QIAGEN) following the manufacturer's recommendations. We …

Antagonistic Pleiotropy In Alzheimer's Disease, Annie Hollis

Undergraduate Research Conference

Apolipoprotein E (APOE) ε4 allele has been linked with Alzheimer’s disease; specifically having two copies of the APOE ε4 allele greatly increases the risk of developing Alzheimer’s disease in older age. Studies have attempted to relate an antagonistic pleiotropy hypothesis to this gene, i.e., the ε4 allele has positive effects on cognition and memory in early life and negative effects later in life. Many of these studies have had several limitations and conflicting results, such as testing adults in upper middle age or comparing the absence of the ε4 allele with the presence of at least one ε4 allele. Studies …

Breast Cancer Subtyping Of The Cancer Genome Atlas (Tcga) Samples, Spencer E. Yu, Alfred B. Amendolara, Steven T. Tung, Alexander P. Sheppert, Nasif Islam, Mindy Cook, Lena Diprizito, Nicole Lashiker, Roshni Jogin, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.

Understanding The Effect Of Adaptive Mutations On The Three-Dimensional Structure Of Rna, Justin Cook

Undergraduate Research and Scholarship Symposium

Single-nucleotide polymorphisms (SNPs) are variations in the genome where one base pair can differ between individuals.¹ SNPs occur throughout the genome and can correlate to a disease-state if they occur in a functional region of DNA.¹According to the central dogma of molecular biology, any variation in the DNA sequence will have a direct effect on the RNA sequence and will potentially alter the identity or conformation of a protein product. A single RNA molecule, due to intramolecular base pairing, can acquire a plethora of 3-D conformations that are described by its structural ensemble. One SNP, rs12477830, which …

Students As Investigators: Utilizing Active Learning To Engage Genetic Counseling Students, Stacey E. Wahl Ph.D., Dana L. Ladd Ph.D.

Transforming Libraries for Graduate Students

Providing one-shot instruction sessions can be difficult, particularly in the graduate learning environment. As librarians, we want to provide students with the skills to search effectively for health information without overwhelming or confusing them. In health science graduate programs, we are expected to connect literature searching skills with the content of the courses in a manner that is engaging to students. This challenge can be exacerbated when students are new to graduate school and have not yet become familiar with scientific literature searching or the research process. Two medical librarians sought to overcome these challenges by empowering genetic counseling students …

Exploration Of Prostate Cancer Cells: The Significance Of Active Herv, Dakota Shepherd

Student Scholar Showcase

The second most common cancer in men is prostate cancer. Prostate cancer is traditionally diagnosed by a digital rectal exam. Blood tests can also be used to test for PSA (prostate-specific antigen). These two methods can be used together but can sometimes provide both false negative and false positive results. A new method of testing for prostate cancer could prove to be beneficial. Previous studies have shown that active HERV sequences have been identified in some cancers, including prostate cancer. We hypothesize that the presence of active HERV in prostate cancer lines is significant. In this study, rabbit polyclonal antibodies …

Updates On Epigenetic Alterations To Brca1: Chemosensitivities, Haley Blum

UNO Student Research and Creative Activity Fair

Breast cancer 1, early onset (BRCA1) is a human tumor suppressor gene encoding the BRCA1 protein that maintains genomic integrity. Molecular events may contribute to the loss of BRCA1 function, contributing to site specific tumorigenesis. Loss of BRCA1 function may arise from mutation or epigenetic events. Germline mutations of BRCA1 have been thoroughly implicated in heritable breast and ovarian cancers. More recently, sporadic breast cancer has been shown to be driven by epigenetic alterations to the BRCA1 promoter region, specifically methylation. Breast carcinomas that present with BRCA1 promoter methylation have been associated with triple negative breast cancers, as well …

A Humanized Hypertrophic Cardiomyopathy Model To Elucidate Molecular Mechanism In Disease Pathology, Ragavi Vijayakumar, Maxine Hong

The International Student Science Fair 2018

Hypertrophic cardiomyopathy (HCM), that clinically manifests as an enlarged heart is a highly prevalent cardiac disorder with propensity towards arrhythmia-induced sudden cardiac death. The mechanism of HCM remains poorly defined, necessitating further understanding of the disease for improved therapeutic strategies. As it is challenging to obtain cardiac biopsies from human subjects, using induced pluripotent stem cells technology, we generated cardiomyocytes (CMs) in a dish from HCM patients. These HCM-CMs presented the clinical manifestation in that they were significantly larger in size in comparison to control (healthy)-CMs. Furthermore, gene expression profiling of cardiac ion channels revealed increased transcripts encoding for calcium …

Genes Associated With Mandibular Prognathism In The Chinese Population, Jacqueline Payne, Marie Tolarova M.D., Ph.D., D.Sc.

Excellence Day

Mandibular prognathism (MP) is the relationship of the mandible anteriorly positioned in relation to the cranial base. The prevalence of MP in Asians is estimated to be 15%, whereas American and European descent exhibit a 5% prevalence. Orthodontic treatment is lengthy and challenging, and severe cases require surgical intervention. However, when a treatment is planned well, the outcomes are predominantly successful. It has been known that genetics are involved in the etiology of prognathism and that greater genetic contribution corresponds to greater challenges to treatment. Thus, there is a desire to determine genes involved in the etiology of prognathism.

The Emerging Genetics Workforce: A Study Of Physician Geneticists' Professional Lives, Heather Gosnell

Posters-at-the-Capitol

PURPOSE: The purpose of this study is to explore the current practice and geographic location trends of physicians certified in clinical genetics, clinical biochemical genetics, and medical biochemical genetics during the 2011, 2013, and 2015 certification cycles.

METHODS: Physicians’ personal data was collected from public internet domains including the American Board of Medical Genetics and Genomics (ABMGG) provider database, the CMS National Plan and Provider Enumeration System, publically available professional-biographies, and university affiliations. The search results were cross-referenced for the greatest accuracy. Geographic location data was plotted onto maps.

RESULTS: Approximately 27% (n=69) physicians board-certified in genetics are currently practicing …