Digital Commons Network^™

A Search For Transcriptional Cofactors Of Gcm/Repo Involved In Determining Glia Cell Fate In Drosophila Melanogaster, Nivedha Kosalram

Honors Theses

In Drosophila melanogaster, the mechanism influencing the differentiation of glia and neurons is directed by a key transcription factor known as glial cells missing (gcm). gcm is a crucial regulator of cell fate decision, functioning as a binary switch to direct glial fate in gcm- positive cells and neuronal fate in gcm-negative cells (Jones, et.al, 1995; Hosoya, et.al, 1995; and Vincent, et.al, 1996). In addition to directing gliogenesis, gcm and its homolog gcm2 facilitate the determination of macrophages and tendon cells, highlighting that gcm acts with supplementary factors to induce various signaling pathways in different contexts (Jones, 2005; Johnson, et …

Improved Outcomes Of Acute Lymphoblastic Leukemia After Allogeneic Blood Or Marrow Transplantation With High-Dose Post-Transplantation Cyclophosphamide In The Era Of More Effective Pre-Transplant Therapy, Jonathan A Webster, Madison Reed, Hua-Ling Tsai, Philip H Imus, Douglas B Smith, Alexander J Ambinder, Mark J Levis, Amy E Dezern, Gabrielle T Prince, Tania Jain, Javier Bolaños-Meade, Lukasz P Gondek, Gabriel Ghiaur, William Brian Dalton, Theodoros Karantanos, Suman Paul, Ephraim J Fuchs, Cole Sterling, Lode J Swinnen, Nina Wagner-Johnston, Richard F Ambinder, Christian B Gocke, Syed Abbas Ali, Carol Ann Huff, Leo Luznik, Ravi Varadhan, Richard J Jones, Ivana Gojo

Faculty, Staff and Students Publications

The therapeutic landscape in ALL has changed dramatically over the last decade. Allogeneic blood or marrow transplantation (AlloBMT) has also evolved and remains an important option for consolidation. We assessed the interplay between these factors by analyzing the outcomes of 251 adult ALL (214 B and 37 T ALL) patients undergoing alloBMT with post-transplantation cyclophosphamide (PTCy) across two eras: 2008-2014 (ERA1) and 2015-2022 (ERA2). ERA1 patients were younger (median age 45.5 vs. 50, p=0.03), less likely to have an HCT-CI ≥4 (9% vs. 21%, p=0.01), more likely to have MRD by flow cytometry (20% vs. 9%, p=0.01) and receive myeloablative …

Zanidatamab Monotherapy Or Combined With Chemotherapy In Her2-Expressing Gastroesophageal Adenocarcinoma: A Phase 1 Trial, Funda Meric-Bernstam, Sun Young Rha, Erika Hamilton, Yoon-Koo Kang, Diana L Hanna, Syma Iqbal, Keun-Wook Lee, Jeeyun Lee, Muralidhar Beeram, Do-Youn Oh, Jorge Chaves, Rachel A Goodwin, Jaffer A Ajani, Lin Yang, Rajen Oza, Elena Elimova

Faculty, Staff and Student Publications

There is a need for novel therapies for patients with previously treated HER2-positive gastroesophageal adenocarcinoma (GEA). This phase 1 (NCT02892123) dose-escalation and expansion trial evaluated zanidatamab (a dual HER2-targeted bispecific antibody) ± chemotherapy in previously treated patients with HER2-expressing, locally advanced/metastatic cancers. Here, we report the outcomes for GEA cohorts receiving zanidatamab monotherapy or with chemotherapy (paclitaxel or capecitabine). The primary endpoint was safety and tolerability. Secondary endpoints were objective response rate (ORR), disease control rate, progression-free survival, pharmacokinetics, and immunogenicity. Seventy patients were enrolled (n = 29 monotherapy; n = 41 combination therapy); most received prior HER2-targeted agents (monotherapy, …

Overconfidence And Financial Risk Tolerance In Older Age, Colleen C Frank, Gary R Mottola, Meiru Chen, Lei Yu, Patricia A Boyle, Gregory R Samanez-Larkin, Kendra L Seaman

Faculty, Staff and Student Publications

Objectives: Excessive financial risk-taking in older age can have harmful consequences as opportunities to recover lost wealth are limited. Understanding financial risk-taking in older age is important for identifying vulnerabilities and developing interventions to empower aging investors to make wise financial choices. In this paper, we explore how overconfidence in financial knowledge affects financial risk-taking among older adults.

Methods: We examine this research question in older adults aged 58-101 (N = 1,242) using data from the Rush Memory and Aging Project (MAP).

Results: After controlling for demographics, overconfidence was associated with self-reported financial risk tolerance such that those who were …

Lifespan Reference Curves For Harmonizing Multi-Site Regional Brain White Matter Metrics From Diffusion Mri, Alyssa H Zhu, Talia M Nir, Shayan Javid, Julio E Villalón-Reina, Amanda L Rodrigue, Lachlan T Strike, Greig I De Zubicaray, Katie L Mcmahon, Margaret J Wright, Sarah E Medland, John Blangero, David C Glahn, Peter Kochunov, Douglas E Williamson, Asta K Håberg, Paul M Thompson, Neda Jahanshad

Faculty, Staff and Student Publications

Age-related white matter (WM) microstructure maturation and decline occur throughout the human lifespan, complementing the process of gray matter development and degeneration. Here, we create normative lifespan reference curves for global and regional WM microstructure by harmonizing diffusion MRI (dMRI)-derived data from ten public datasets (N = 40,898 subjects; age: 3-95 years; 47.6% male). We tested three harmonization methods on regional diffusion tensor imaging (DTI) based fractional anisotropy (FA), a metric of WM microstructure, extracted using the ENIGMA-DTI pipeline. ComBat-GAM harmonization provided multi-study trajectories most consistent with known WM maturation peaks. Lifespan FA reference curves were validated with test-retest data …

Axl Promotes Inflammatory Breast Cancer Progression By Regulating Immunosuppressive Macrophage Polarization, Lan T H Phi, Yating Cheng, Yohei Funakoshi, Francois Bertucci, Pascal Finetti, Steven J Van Laere, Fang Zou, James P Long, Suguru Ogata, Savitri Krishnamurthy, James M Reuben, Jason M Foulks, Steven L Warner, Jennifer M Rosenbluth, Anil K Sood, Debu Tripathy, Naoto T Ueno, Xiaoping Wang

Faculty, Staff and Student Publications

Background: Tumor-associated macrophages (TAMs) are key promoters of inflammatory breast cancer (IBC), the most aggressive form of breast cancer. The receptor tyrosine kinase AXL is highly expressed in various cancer types, including IBC, but its role in TAMs remains unexplored.

Methods: We examined the effects of AXL inhibitor TP-0903 on tumor growth and tumor microenvironment (TME) component M2 macrophages (CD206+) in IBC and triple-negative breast cancer mouse models using flow cytometry and immunohistochemical staining. Additionally, we knocked out AXL expression in human THP-1 monocytes and evaluated the effect of AXL signaling on immunosuppressive M2 macrophage polarization and IBC cell growth …

Catecholaminergic Polymorphic Ventricular Tachycardia-Linked Ryanodine Receptor Variants Exhibit Domain-Specific Calcium Leak And Calmodulin Affinity Properties, Hitoshi Uchinoumi, Xiaoqiong Dong, Ivanita Stefanon, Yi Yang, Eduardo Hertel Ribeiro, Bengt Svensson, Xander H T Wehrens, Takeshi Yamamoto, Razvan L Cornea, Robyn T Rebbeck, Masafumi Yano, Donald M Bers

Faculty, Staff and Students Publications

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited stress-induced arrhythmogenic disease often caused by point variants in the cardiac ryanodine receptor (RyR2) that enhance diastolic sarcoplasmic reticulum (SR) Ca2+ leak. These RyR2 variants cluster in three hot-spots (N-terminal, central and C-terminal domains). We previously demonstrated a pathologic diastolic RyR2 conformation in heart failure, oxidative stress and CaMKII phosphorylation exhibiting a trilogy of effects: (1) reduced calmodulin (CaM)-RyR2 affinity, (2) enhanced unzipping peptide (DPc10) binding and (3) elevated diastolic SR Ca2+ leak that are dantrolene-sensitive. Here we test whether this pathological trilogy occurs in CPVT knock-in (KI) mice bearing N-terminal (R176Q/+), …

Protocol For A Randomized Controlled Trial To Determine If Biomarkers Predict Response To A Pediatric Chronic Pain Symptom Management Program, Rona L Levy, Tasha B Murphy, Margaret M Heitkemper, Miranda A L Van Tilburg, Ann R Mcmeans, Jocelyn Chang, Cynthia Boutte, Katherine Lamparyk, Bruno P Chumpitazi, Robert J Shulman

Children’s Nutrition Research Center Staff Publications

Background/Objectives: Disorders of gut-brain interaction (DGBI), characterized by chronic abdominal pain and significant disability, affect 15-20% of children and adults and continue into adulthood in ~60% of cases. Costs for adults reach USD 30 billion per year, yet effective management strategies are elusive. Studies support using cognitive behavioral therapy (CBT), but abdominal pain only improves in ~40% of patients. Dietary management (low FODMAP diet; LFD) has also shown promise but it is effective in only a similar percentage of patients. Studies suggest that biologic factors (biomarkers) contribute to CBT response. Similarly, gut microbiome composition appears to influence abdominal pain …

Gut Dysbiosis Patterns In Cvid Patients With Noninfectious Complications Observed In A Germ-Free Mouse Model Through Fecal Microbiota Transplantation, Joud Hajjar, Anita Y Voigt, Margaret E Conner, Alton G Swennes, Stephanie Fowler, Chadi Calarge, Danielle D Mendonca, Dominique Armstrong, Chen-Yen Chang, Jolan E Walter, Manish J Butte, Tor Savidge, Julia Oh, Farrah Kheradmand, Joseph F Petrosino

Faculty, Staff and Students Publications

Patients with common variable immunodeficiency (CVID) who develop noninfectious complications (NIC) have worse clinical outcomes than those with infections only (INF). While gut microbiome aberrations have been linked to NIC, reductionist animal models that accurately recapitulate CVID are lacking. Our aim in this study was to uncover potential microbiome roles in the development of NIC in CVID. We performed whole-genome shotgun sequencing on fecal samples from CVID patients with NIC, INF, and their household controls. We also performed fecal microbiota transplants from CVID patients to germ-free mice. We found potentially pathogenic microbes

Protocol For A Randomized Controlled Trial To Determine If Biomarkers Predict Response To A Pediatric Chronic Pain Symptom Management Program, Rona L Levy, Tasha B Murphy, Margaret M Heitkemper, Miranda A L Van Tilburg, Ann R Mcmeans, Jocelyn Chang, Cynthia Boutte, Katherine Lamparyk, Bruno P Chumpitazi, Robert J Shulman

Faculty, Staff and Students Publications

Background/Objectives: Disorders of gut-brain interaction (DGBI), characterized by chronic abdominal pain and significant disability, affect 15-20% of children and adults and continue into adulthood in ~60% of cases. Costs for adults reach USD 30 billion per year, yet effective management strategies are elusive. Studies support using cognitive behavioral therapy (CBT), but abdominal pain only improves in ~40% of patients. Dietary management (low FODMAP diet; LFD) has also shown promise but it is effective in only a similar percentage of patients. Studies suggest that biologic factors (biomarkers) contribute to CBT response. Similarly, gut microbiome composition appears to influence abdominal pain …

Language Mapping During Awake Brain Surgery In A Deaf Patient With A Brain Tumor: Illustrative Case, Ene Chibawanye I, Elizabeth Silva, Kyle Noll, Mariana Bradshaw, Katherine Connelly, Ho-Ling Liu, Ravi Tummala, David Ferson, Frederick F Lang, Vinodh A Kumar

Faculty, Staff and Student Publications

Background: Signed language integrates complex sensorimotor processes involving visual and motor networks. The contribution of language regions such as Broca's and Wernicke's areas during signing is not well established. Here, the authors report the case of a 45-year-old right-handed male with congenital deafness, who communicates using American Sign Language (ASL) and Signed English, presenting with focal seizures. Imaging showed a diffuse infiltrative glioma in the right cerebral hemisphere.

Observations: Remarkably, preoperative functional MRI language activations were bihemispheric and overlapped for both traditional language paradigms and sign paradigms, suggesting that the same cortical regions of the brain are used for language …

Division Iii Soccer Athlete Ankle Stability In An Ankle Brace Compared To Ankle Tape During Functional Testing, Caitlin M. Craig

Masters Theses/Capstone Projects

Objective/ Context: A common injury to athletes and non-athletes is a lateral ankle sprain. There is a higher incidence of a lateral ankle sprain occurring during sports participation. Additionally, soccer athletes are at an increased risk for lateral ankle injuries due to the high impact of cutting and turning, which can lead to the mechanism of injury. As a means of injury prevention and ankle stability, ankle taping and ankle bracing provide athletes with similar support. There is an ongoing debate on whether one method is better at providing stability to at-risk populations; however, the answer is still being determined. …

A Sumo-Interacting Motif In The Guanine Nucleotide Exchange Factor Epac1 Is Required For Subcellular Targeting And Function, Wenli Yang, Fang Mei, Wei Lin, Jason E Lee, Si Nie, Christopher J Bley, André Hoelz, Xiaodong Cheng

Faculty, Staff and Students Publications

Exchange protein directly activated by cAMP (EPAC1), a multifunctional intracellular cAMP receptor, dynamically localizes to various cellular loci, engaging with diverse molecular partners to maintain cellular homeostasis. The study investigates the role of the SUMO interacting motif (SIM) in the subcellular targeting and cellular functions of EPAC1. It reveals that the SIM is a critical structural element for EPAC1's association with RanBP2/Nup358, a nucleoporin of the cytoplasmic filament component of the nuclear pore complex (NPC). Mutational disruption of EPAC1 SIM interferes with EPAC1's ability to activate its canonical effectors, small GTPases, Rap1 and Rap2, and non-canonical functions, such as the …

Alzheimer’S Disease Protective Allele Of Clusterin Modulates Neuronal Excitability Through Lipid-Droplet-Mediated Neuron-Glia Communication, Xiaojie Zhao, Yan Li, Siwei Zhang, Ari Sudwarts, Hanwen Zhang, Alena Kozlova, Matthew J Moulton, Lindsey D Goodman, Zhiping P Pang, Alan R Sanders, Hugo J Bellen, Gopal Thinakaran, Jubao Duan

Duncan NRI Faculty and Staff Publications

Background: Genome-wide association studies (GWAS) of Alzheimer's disease (AD) have identified a plethora of risk loci. However, the disease variants/genes and the underlying mechanisms have not been extensively studied.

Methods: Bulk ATAC-seq was performed in induced pluripotent stem cells (iPSCs) differentiated various brain cell types to identify allele-specific open chromatin (ASoC) SNPs. CRISPR-Cas9 editing generated isogenic pairs, which were then differentiated into glutamatergic neurons (iGlut). Transcriptomic analysis and functional studies of iGlut co-cultured with mouse astrocytes assessed neuronal excitability and lipid droplet formation.

Results: We identified a putative causal SNP of CLU that impacted neuronal chromatin accessibility to transcription-factor(s), with …

Editorial–Special Issue On Application Of Cold Atmospheric Plasma In Human And Veterinary Disease, Katharina Stapelmann, Eloisa Sardella, Vandana Miller

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Plasma medicine is a rapidly evolving interdisciplinary field that combines plasma science and engineering, chemistry, biology, and medicine. This special issue focuses on various ways to apply cold atmospheric pressure plasma in translating plasma technology into clinical applications. Ongoing research on the redox-based mechanism of plasma action, the concept of 'plasma dose' and device control is critical for advancing plasma medicine. As these applications move toward the clinic, ensuring the reproducibility and quality control of plasma sources is essential. The articles in this issue present examples of both direct and indirect plasma applications, with indirect treatments describing cell exposure to …

Reexploring The Stress Trial: Subgroup Postoperative Outcomes Following Methylprednisolone For Infant Heart Surgery, Sudeep D Sunthankar, Kevin D Hill, Jeffrey P Jacobs, H Scott Baldwin, Marshall L Jacobs, Jennifer S Li, Eric M Graham, Ashraf M Resheidat, Venugopal Amula, Mark S Bleiweis, Eric L Wald, Pirooz Eghtesady, John P Scott, Brett R Anderson, Michael F Swartz, Alexis Benscoter, William Ravekes, Prince J Kannankeril

Faculty, Staff and Students Publications

Objective Assess the association between intraoperative methylprednisolone and specific postoperative outcomes among subgroups undergoing infant heart surgery.

Design: Subpopulation analyses of The Steroids to Reduce Systemic Inflammation after Infant Heart Surgery trial, a double-blind randomized placebo-controlled trial.

Setting: 24 congenital heart centers.

Patients: Infants (< 1 year old) undergoing heart surgery with cardiopulmonary bypass. Patients stratified by Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery (STAT) Mortality Category, age, gestational age, and presence of chromosomal or syndromic diagnosis (CSD).

Interventions: Methylprednisolone (30 mg/kg) versus placebo administered into cardiopulmonary bypass pump-priming fluid.

Measurements and main results: Outcomes included death, heart transplantation, mechanical circulatory support, reinterventions, and hospital length of stay. Ranked composite outcome (death, transplant, or one of 13 major complications) was compared between placebo and methylprednisolone for each subgroup using the win ratio. Methylprednisolone …

Design And Assembly Of A Lightweight, Multi-Cannula Tetrode Drive For Bilateral Hippocampal And Acc Recordings, Homero Phelps, Jasmine Sidhu, Jonathan V. Trinidad, Talha Soluoku

Undergraduate Research Symposium Posters

Implants and Electrophysiology:

Electrophysiology is the study of the electrical properties of cells and tissues, neuronal implants enable high-resolution recordings of neuron action potentials and their locations in the brain.

Data gathered is key in investigating/mapping cognition and effects of neurological pathologies on regular neural systems.

Hyperdrive Model:

Previous model was restricted to two implant sites, and displayed frequent tetrode deformation

Hyperdrive was modified to support four implant sites and 16 independently movable tetrodes using 3D modeling software, while keeping its weight below 1.5 grams.

Targets:

Researchers targeted the hippocampus (CA1, CA3) and ACC, using the novel bilateral model

Crispr/Ncas9-Edited Cd34+ Cells Rescue Mucopolysaccharidosis Iva Fibroblasts Phenotype, Angélica María Herreno-Pachón, Andrés Felipe Leal, Shaukat Khan, Carlos Javier Alméciga-Díaz, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidosis (MPS) IVA is a bone-affecting lysosomal storage disease (LSD) caused by impaired degradation of the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin 6-sulfate (C6S) due to deficient N-acetylgalactosamine-6-sulfatase (GALNS) enzyme activity. Previously, we successfully developed and validated a CRISPR/nCas9-based gene therapy (GT) to insert an expression cassette at the AAVS1 and ROSA26 loci in human MPS IVA fibroblasts and MPS IVA mice, respectively. In this study, we have extended our approach to evaluate the effectiveness of our CRISPR/nCas9-based GT in editing human CD34+ cells to mediate cross-correction of MPS IVA fibroblasts. CD34+ cells were electroporated with the CRISPR/nCas9 system, …

Genomic Characterization Of High-Grade Serous Ovarian Carcinoma Reveals Distinct Somatic Features In Black Individuals, Katherine A Lawson-Michod, Jeffrey R Marks, Lindsay J Collin, David A Nix, Natalie R Davidson, Chad D Huff, Yao Yu, Aaron Atkinson, Courtney E Johnson, Lucas A Salas, Lauren C Peres, Casey S Greene, Joellen M Schildkraut, Jennifer A Doherty

Faculty, Staff and Student Publications

Black individuals experience worse survival after a diagnosis of high-grade serous ovarian carcinoma (HGSC) than White individuals and are underrepresented in ovarian cancer research. To date, the understanding of the molecular and genomic heterogeneity of HGSC is based primarily on the evaluation of tumors from White individuals. In the present study, we performed whole-exome sequencing on HGSC samples from 211 Black patients to identify significantly mutated genes and characterize mutational signatures, assessing their distributions by gene expression subtypes. The occurrence and frequency of somatic mutations and signatures by self-reported race were compared with historic data from The Cancer Genome Atlas …

Advancing Research On Retinitis Pigmentosa: An Investigation Of Natural History, Visual System Plasticity, And Mutation-Independent Treatment., Cecilia A. Attaway

Electronic Theses and Dissertations

Retinitis Pigmentosa (RP) is an inherited retinal disease characterized by rod and then cone photoreceptor degeneration. ~25% of cases are caused by a genetic mutation that results in autosomal dominant RP (adRP). There has been a lack of exploration of the progression of degeneration in adRP models. In Chapter Two, I examined visual acuity (VA) changes, retinal structure, and function from early to late-stage disease in a murine P23H Rho ‘knock-in’ mouse model (Rho^P23H/+), the most common form of adRP in North America. To establish a natural history, I evaluated behavioral VA, using the visual water task, …

Spaceflight Associated Neuro-Ocular Syndrome (Sans) And Its Countermeasures, Tuan Nguyen, Joshua Ong, Tyson Brunstetter, C Robert Gibson, Brandon R Macias, Steven Laurie, Thomas Mader, Alan Hargens, Jay C Buckey, Mimi Lan, Peter Wostyn, Cihan Kadipasaoglu, Scott M Smith, Sara R Zwart, Benjamin J Frankfort, Sarah Aman, Jessica M Scott, Ethan Waisberg, Mouayad Masalkhi, Andrew G Lee

Faculty, Staff and Students Publications

Astronauts can develop a distinct collection of neuro-ophthalmic findings during long duration spaceflight, collectively known as Spaceflight Associated Neuro-ocular Syndrome (SANS). These clinical characteristics include optic disc edema, hyperopic refractive shifts, globe flattening, and chorioretinal folds, which may pose a health risk for future space exploration. Obtaining knowledge of SANS and countermeasures for its prevention is crucial for upcoming crewed space missions and warrants a multidisciplinary approach. This review examines the potential causes and countermeasures of SANS, including space anticipation glasses, lower body negative pressure, venoconstrictive thigh cuffs, impedance threshold devices, translaminar pressure gradient modulation, centrifugation, artificial gravity, pharmaceuticals, and …

Reducing Diabetic Ketoacidosis Incidence In Children With Type 1 Diabetes Through Wraparound Services At Texas Children's Hospital: The Reach Program, Selorm Dei-Tutu, Fulfilled Ighalo, Pavandeep Rakhra, Rebecca Butler, Amelia Martinez, Kelly Timmons, Don Buckingham, David D Schwartz, Meghan Craven

Faculty, Staff and Students Publications

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of

A Comprehensive Literature Review Of Barriers To Hormone Therapy Utilization: Strategies For Improving Menopause Management In Women Aged 40-60, Suhan Lee

Capstone Experience: Master of Public Health

Menopause is a natural transition marked by the cessation of ovarian activity, often accompanied by vasomotor symptoms (VMS), genitourinary syndrome of menopause (GSM), and psychological changes that significantly impact women’s quality of life. Hormone therapy (HT) has been the primary treatment for managing menopausal symptoms, particularly VMS, providing substantial relief when initiated within 10 years of menopause. Despite its effectiveness, HT usage has declined dramatically over the past two decades primarily due to barriers such as stigma, safety, misinformation, provider hesitancy, financial barriers, and cultural beliefs. This comprehensive literature review explores key factors influencing HT decision-making, including the media’s role …

Mechanisms Of Behavioral Change In Hosts Of Toxoplasma Gondii: A Review, Olivia Grimsley

Senior Honors Theses

The parasite Toxoplasma gondii is a highly ubiquitous parasite that latently infects an estimated 33% percent of the global population. Toxoplasmosis is of obvious clinical significance due to the extremely high risks to the unborn who contract it congenitally. Less attention has been given to a more subtle aspect of latent infection, which is the behavioral alterations that are commonly experienced by those who contract the parasite. Infected individuals commonly display a variety of altered behaviors, such as increased aggression and risk-seeking behaviors, depression, higher tendency towards suicide and self-directed violence, a loss of fear response, and a greatly increased …

Sodium And Potassium In Health And Cellular Function, Jordyn Branz

Honors Program: Senior Projects (Public)

Sodium (Na⁺) and potassium (K⁺) are essential electrolytes that regulate numerous physiological processes. These include cell function, nerve transmission, and muscle contraction. The Na+/K+-ATPase plays a critical role in maintaining the balance of these ions by actively transporting three sodium ions out of the cell and two potassium ions into the cell against their concentration gradients. This process is vital for maintaining the resting membrane potential and supporting the function of excitable cells. The Na+/K+-ATPase consists of two main subunits, with the alpha-subunit being primarily responsible for ion transport activity. Isoforms alpha1, alpha2, and alpha3 are tissue-specific and contribute to …

Alphamissense Predictions And Clinvar Annotations: A Deep Learning Approach To Uveal Melanoma, David J. Taylor Gonzalez, Mak B. Djulbegovic, Meghan Sharma, Michael Antonietti, Colin K. Kim, Vladimir N. Uversky, Carol L. Karp, Carol L. Shields, Matthew W. Wilson

Wills Eye Hospital Papers

OBJECTIVE: Uveal melanoma (UM) poses significant diagnostic and prognostic challenges due to its variable genetic landscape. We explore the use of a novel deep learning tool to assess the functional impact of genetic mutations in UM.

DESIGN: A cross-sectional bioinformatics exploratory data analysis of genetic mutations from UM cases.

SUBJECTS: Genetic data from patients diagnosed with UM were analyzed, explicitly focusing on missense mutations sourced from the Catalogue of Somatic Mutations in Cancer (COSMIC) database.

METHODS: We identified missense mutations frequently observed in UM using the COSMIC database, assessed their potential pathogenicity using AlphaMissense, and visualized mutations using AlphaFold. Clinical …

A Comparative Analysis Of Nf-Κb1 Gene Regulatory Sequence Methylation In Normotensive And Hypertensive Kenyans, Aaryan Barlas Piracha

Honors Theses

Accounting for the majority of deaths worldwide, non-communicable diseases (NCDs) present the greatest health challenge of the twenty-first century. Specifically, cardiovascular diseases (CVDs) exceed all other NCDs in annual deaths and especially affect low- and middle-income countries (LMICs). Hypertension, being the primary risk factor for CVD, affects over 75% of adults in LMICs due to inadequate health care and preventative measures. Additionally, epigenetic modifications of DNA are important mechanisms that regulate gene expression; DNA methylation, in particular, affects cytosine residues in cytosine-phosphate-guanine (CpG) islands on regulatory sequences. Previous research in our laboratory analyzed percent methylation at 8 different CpG islands …

Pseudomonas Aeruginosa Exoenzyme Y Enzymatic Activity Inhibits Exoenzyme S-Induced Caspase Activation But Not Cytotoxicity In Pulmonary Microvascular Endothelial Cells, Connor Holm

Honors Theses

Pseudomonas aeruginosa (P. aeruginosa) is the most common cause of ventilator-associated pneumonia in intensive care unit patients. P. aeruginosa utilizes a type III secretion system that injects exoenzymes U, S, T, and/or Y into the host cell cytosol. A majority of clinically isolated P. aeruginosa strains express ExoY often in combination with ExoU and ExoT, or ExoS and ExoT. Host signaling mechanisms in response to intoxication with individual exoenzymes have been extensively studied, yet little is known about host cell response to co-intoxication. In this study, pulmonary microvascular endothelial cells (PMVECs) were infected with P. aeruginosa strains expressing different combinations …

Clinical, Immunologic, And Genetic Characteristics Of 148 Patients With Natural Killer Cell Deficiency, Manar Abdalgani, Evelyn R Hernandez, Luis A Pedroza, Ivan K Chinn, Lisa R Forbes Satter, Nicholas L Rider, Pinaki P Banerjee, M Cecilia Poli, Sanjana Mahapatra, Debra Canter, Tram Cao, Linda M Shawver, Sarada L Nandiwada, James R Lupski, Jennifer E Posey, Rajasekhar Ramakrishnan, Emily M Mace, Jordan S Orange

Faculty, Staff and Students Publications

Background: Natural killer (NK) cell deficiency (NKD) is an immunodeficiency phenotype in which abnormality of NK cells is the major clinically relevant immune defect.

Objective: We sought to define the clinical, immunologic, and genetic characteristics of patients with NKD to aid in the understanding of these individuals and this cell type and guide future research and clinical practice.

Methods: During 2006-2022, 168 individuals with a suspected diagnosis of NKD were enrolled, with comprehensive clinical, immunologic, and genetic data collected and analyzed. Research exome sequencing was performed to identify both known and novel genetic associations.

Results: NK cell abnormalities consistent with …

Tau Depletion Diminishes Vascular Amyloid-Related Deficits In A Mouse Model Of Cerebral Amyloid Angiopathy, Nur Jury-Garfe, Enrique Chimal-Juárez, Henika Patel, Jonathan Martinez-Pinto, Kathryn Vanderbosch, Muriel D Mardones, Abigail Perkins, Gonzalo Viana Di Prisco, Yamil Marambio, Ruben Vidal, Brady K Atwood, Cristian A Lasagna-Reeves

Faculty, Staff and Students Publications

Introduction: Tau is essential for amyloid beta (Aβ)-induced synaptic and cognitive deficits in Alzheimer's disease (AD), making its downregulation a therapeutic target. Cerebral amyloid angiopathy (CAA), a major vascular contributor to cognitive decline, affects over 90% of patients with AD. This study explores the impact of tau downregulation on CAA pathogenesis.

Methods: We crossed the Familial Danish Dementia mouse model (Tg-FDD), which develops vascular amyloid, with tau-null (mTau-/-) mice to generate a CAA model lacking endogenous tau (Tg-FDD/mTau-/-). Behavioral, electrophysiological, histological, and transcriptomic analyses were performed.

Results: Tau depletion ameliorated motor and synaptic impairments, reduced vascular amyloid deposition, and prevented …