Digital Commons Network^™

Variation In Antiviral Immunity And Inflammation Pathways Precedes Hiv-1 Infection In A High-Risk African Cohort, Mwikali Kioko, Shaban Mwangi, Lynn Fwambah, Amin Hassan, Jason Blackard, Philip Bejon, Eduard Sanders, Thumbi Ndung’U, Eunice Nduati, Abdirahman Abdi

Institute for Human Development, East Africa

BACKGROUND. Susceptibility to HIV-1 infection varies between individuals, but the biological determinants of acquisition risk remain poorly defined.

METHODS. We conducted a case-control study nested within a high-risk cohort in Kenya. We compared the plasma extracellular RNA collected before HIV-1 acquisition with that from matched uninfected individuals acting as controls to identify immunological processes linked to infection risk.

RESULTS. Individuals who later acquired HIV-1 exhibited upregulation of immune processes that facilitate viral infection, including T cell suppression and type II IFN and Th2 immune responses. In contrast, processes associated with antiviral defence and tissue repair, such as …

Elevated Serum Lipopolysaccharides And Intrinsic Factor Autoantibodies Correlate With Macrocytic Anemia Among People With Hiv, Daniel Amakye, Samuel Hammond, Osbourne Quaye, Upal Roy, Peter Puplampu, Vincent Ganu, Emmanuel Ayitey Tagoe

Health & Biomedical Sciences Faculty Publications

Introduction: Human immunodeficiency virus (HIV) infection is associated with various comorbidities, including macrocytic anemia, though the role of the infection is unclear. HIV has been implicated in microbial translocation and altered immune responses. This study aimed to establish the relationship between gut microbial translocation and immune response, and macrocytic anemia among people with HIV (PWH).

Materials and methods: Fifty-five PWH on combination antiretroviral therapy (cART) were age-matched with 55 HIV-negative individuals. Demographic data and blood samples were collected from February to July 2023. Hematological indices, including red blood cell (RBC) count, hemoglobin concentration, and mean corpuscular volume (MCV), were measured. …

Recommended Best Practices For Construct-Centered Adaptation Of The Harmonized Cognitive Assessment Protocol, Emily M. Briceño, Darina T. Bassil, Pranali Khobragade, Anthony Ngugi, Martine El Bejjani, Eric Ochieng, Silvia Mejia-Arango, Salima Douhou, Kazione Kulisewa

School of Medicine Publications

Objectives: The Harmonized Cognitive Assessment Protocol (HCAP) neuropsychological assessment approach aims to support the collection of harmonizable data on cognitive function for cross-national cognitive aging and dementia research. As the measurement of cognition is sensitive to differences in contextual, cultural, educational, linguistic, social, and other factors that may influence cognitive test performance, HCAP requires adaptation to be appropriate for the contexts in which it is administered. We aim to provide methodological recommendations for the adaptation and implementation of the HCAP and other cognitive data collection tools in novel settings.

Methods: We drew from existing guidelines on cross-cultural psychological test adaptation …

A Narrative Review On The Therapeutic Potential Of Stem Cells In Neurodegenerative Diseases: Advances, Insights, And Challenges, Tirath Patel, Fathimathul Henna, Iman Sharif, Inaya Javed, Fatima Mustafa, Hannan Sharif, Fatima Nasir, Mirat Javaid

School of Medicine Publications

Background: Neurodegenerative diseases (NDs) such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) are set apart by progressive neuronal loss and concomitant functional decline. Traditional therapies are equipped with only symptomatic relief, devoid of neurorestorative properties. Stem-cell-based therapies have the potential to revolutionize neurological care by replenishing lost cells, mitigating inflammation, and fostering a neuroprotective environment.

Objectives: This narrative review aims to appraise the treatment potential of various stem cell types in managing NDs, highlighting their functional pathways, delivery methods, and current experimental validation.

Methods: A comprehensive literature search was carried out based on …

Effects Of Peripheral Sympathetic Denervation On Phytohemagglutinin (Pha) Induced Cutaneous Swelling In The Hock And Tail Of Mice, Ayusha Pokharel '27, Masyn Naegele '26

Annual Student Research Poster Session

The sympathetic nervous system (SNS) carries stress signals directly to the site of injury and activates the immune system via direct neuronal innervation or release of systemic hormones. 6-hydroxydopamine (6-OHDA) is a neurotoxin that causes denervation of the SNS by eliminating the peripheral nerve terminals, which are responsible for sending the stress signals. The effect of sympathetic denervation on the localized immune response is unexplored in the literature. Therefore, our study aims to investigate the effect of 6-OHDA-induced sympathetic denervation on local inflammation following phytohemagglutinin (PHA)-induced swelling. Even under resting circumstances, some baseline level of stress is communicated to the …

Investigating The Effects Of Novel Hexylamine Compounds On Hn6 Carcinoma Cell Survival, Lydia Neven '27, Dominic Pittman '26

Annual Student Research Poster Session

Cancer is a broad term encompassing hundreds of distinct diseases, each arising from unique genetic and environmental factors. Because of this diversity, there is a continual need to develop new chemotherapies. Oral cancer, in particular, remains one of the most common cancers worldwide, yet effective therapeutic options for this malignancy remain limited. Although billions of dollars are invested annually in cancer drug discovery in the United States, the process of evaluating and advancing candidate compounds often represents a critical bottleneck, leading many promising therapies to be abandoned before their full potential is understood. In collaboration with the Hansen lab, we …

Pregnancy Outcomes Among Women With And Without Hiv Infections Who Underwent Excisional Treatment For High-Grade Cervical Intraepithelial Neoplasia: A Retrospective Cohort Study In Low-Resource Settings, Poli Amubuomombe, Peter Itsura, Philiph Tonui, Elkanah Orang'o, Benjamin Odongo, Patrick Loehrer, Susan Cu-Uvin

Obstetrics and Gynaecology, East Africa

Objective The standard treatment for high-grade squamous intraepithelial lesions is excisional involving the uterine cervix, while surveillance is an acceptable approach for low-grade squamous intraepithelial lesions. There is controversy about excisional treatment on pregnancy outcomes. The objective of this study was to determine pregnancy outcomes in women living with and without HIV who underwent excisional treatment for high-grade cervical intraepithelial lesions.

Design This retrospective cohort study compared the pregnancy outcomes of women with and without HIV who were or were not treated for cervical intraepithelial lesions. A cohort of 488 women with and without HIV infection who did or did …

Longitudinal Peripheral Blood Transcriptomics Reveal Novel Signatures During Cardiac Allograft Rejection., Rachad Ghazal, Min Wang, Akshatha N. Srinivas, Jenny J. Cao, Hridyanshu Vyas, Duan Liu, Asha Nair, Byron H. Smith, Li Wang, Daniel S. Yip, Parag C. Patel, David E. Steidley, Brian W. Hardaway, Alfredo L. Clavell, Sudhir S. Kushwaha, Walter D. Park, Mark D. Stegall, Howard Eisen, Naveen L. Pereira

Division of Cardiology Faculty Papers

Background: Acute cellularrejection (ACR) remains a major cause of morbidity afterhearttransplantation despite advances in immunosuppression. Whole genometranscriptomicprofiling offers a systems-based, unbiased approach to elucidate the molecular mechanisms underlying ACR. However, noninvasive,longitudinal biomarker assessments capable of capturing the temporal dynamics ofrejection biology remain scarce.

Methods: RNA sequencing ofperipheralblood fromheart transplant recipients before, during, and after ACR was compared with nonrejection controls. Pathway analysis was conducted using differentially expressed genes (DEGs), and a machine learning approach was applied to assessgene-based prediction of ACR.

Results: A total of 235 rejection-specific significant DEGs and 863 postrejection DEGs (false discovery rate < 0.05) were identified. During ACR, DEGs were enriched for T-cell activation/differentiation, apoptosis, and B-cell receptor signaling pathways. By combining the 2 sets of DEGs, a panel of 71 common genes was identified that reflected the significant, longitudinal transcriptomic dynamics of ACR. In an elastic net machine learning-based classifier, DYNLL1 and SERF2 were …

Ubiquitination Of Oncogenic Mutant P53 Via Attenuation Of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth, Mudassier Ahmad, Sahir Sultan Alvi, Haider Ahsan, Carlos Perez, Vivek Kashyap, Neeraj Chauhan, Dae Joon Kim, Nirakar Sahoo, Tamer Oraby, Murali Yallapu, Subhash Chuahan, Bilal Hafeez

School of Medicine Publications

Dysregulated ribosome biogenesis and p53 mutations are known to play oncogenic roles in various cancers, including pancreatic cancer. In this study, we demonstrated the therapeutic potential of BMH-21, a pharmacologic inhibitor of RNA polymerase I, against pancreatic cancer by uncovering a novel molecular mechanism involving RPA194-mediated ubiquitination of mutant p53 without affecting the ubiquitination of wild-type p53. Our key findings are that (i) BMH-21 selectively induces apoptosis and cell growth inhibition of pancreatic cancer cells with no effect on normal human pancreatic ductal epithelial cells; (ii) BMH-21 degrades RPA194; (iii) BMH-21 inhibits recruitment of both RPA194 and RPA135 on rDNA …

Cellstaar: Incorporating Single-Cell-Sequencing-Based Functional Data To Boost Power In Rare Variant Association Testing Of Noncoding Regions, Eric Van Buren, Yi Zhang, Xihao Li, Margaret Sunitha Selvaraj, Zilin Li, Nicholette D. Palmer, Donna K. Arnett, John Blangero, Eric Boerwinkle, Joanne E. Curran, Ravi Duggirala

School of Medicine Publications

Understanding how rare genetic variants influence complex traits remains a major challenge, particularly when these variants lie in noncoding regions of the genome. The effects of variants within candidate cis-regulatory elements (cCREs) often depend on the cell type, making interpretation difficult. Here we introduce cellSTAAR, which integrates whole-genome sequencing data with single-cell assay for transposase-accessible chromatin using sequencing data to capture variability in chromatin accessibility across cell types via the construction of cell-type-specific functional annotations and regulatory elements. To reflect the uncertainty in cCRE–gene linking, cellSTAAR uses a comprehensive strategy to link cCREs to their target genes. We applied …

Prediabetes Associates With Musculoskeletal Alterations Independent Of Total Body Adiposity, Alan Fappi, Clifton J Holmes, Chao Cao, Vasavi Shabrish, Aman P Aher, Karen Shen, Paul K Commean, Dwight A Towler, Dominic N Reeds, Gretchen A Meyer, Bettina Mittendorfer

2020-Current year OA Pubs

BACKGROUND: Excess adiposity is a major risk factor for insulin resistance, prediabetes, and Type 2 diabetes and increases the risk for sarcopenia and osteosarcopenia later in life. It has been proposed that altered metabolic function and musculoskeletal status in people with obesity are directly linked, presumably because they share common pathophysiological mechanisms. However, the effect of metabolic dysfunction, independent of adiposity, on musculoskeletal status is unknown.

METHODS: We performed a comprehensive assessment of musculoskeletal status in people with overweight/obesity and prediabetes (n = 12; 72% women; age: 67 ± 6 years; weight: 81 ± 11 kg; mean ± SD) and …

In-Silico Trial Of Same-Day Simulation-Free Spatially Fractionated Adaptive Radiotherapy (Sf2-Art), Dennis N Stanley, Alyssa R Birchmeier, Carlos E Cardenas, Richard A Popple, Natalie Viscariello, Joel A Pogue, Courtney B Stanley, Mehran Yusuf, Michael Soike, Samuel R Marcrom, Joseph Harms

2020-Current year OA Pubs

PURPOSE: Here we present an in-silico trial of the feasibility and deliverability of a same-day, simulation-free workflow for spatially fractionated adaptive radiotherapy (SF

METHODS AND MATERIALS: Ten patients (five thoracic and five extremity), previously treated with spatially fractionated radiotherapy (SFRT), were selected for this in silico trial. A two-phase regimen was simulated: Phase 1 delivered 12 Gy SBRT to a uniform, predefined high-dose lattice and 4 Gy to the gross tumor volume (GTV); Phase 2 consisted of 4 additional fractions of 4 Gy to the GTV. The planning workflow was performed entirely in silico, without the need for CT simulation. …

How To Measure, Analyze, And Interpret Age-Related Changes In Caenorhabditis Elegans: Lessons For Mechanistic And Evolutionary Theories Of Aging, Zuzana Kocsisova, Brian M Egan, Andrea Scharf, Xavier Anderson, Franziska Pohl, Aaron Anderson, Kerry Kornfeld

2020-Current year OA Pubs

Aging is characterized by progressive degenerative changes in tissue organization and function, some of which increase the probability of mortality. Major goals of aging research are to elucidate the series of events that cause degenerative changes, and to identify environmental, pharmacological, and genetic factors that influence these changes; this information might lead to new strategies to extend health span and lifespan. Mechanistic studies of aging depend on accurate and precise descriptions of age-related changes, since these descriptions define the aging phenotype. Here, we review studies that describe age-related changes in C. elegans, including measurements of integrated functions such as behavior …

Carbohydrate Restriction Drives Greater Perturbations In Circulating Metabolites Than Low Energy Availability In Elite Male Athletes, Kyle A. Dunlop, Nathan G. Lawler, Jamie Whitfield, Alannah K.A. Mckay, Nicolin Tee, Megan L. Ross, Stacey N. Reinke, John A. Hawley, David Broadhurst, Louise M. Burke

Research outputs 2022 to 2026

Periods of low energy availability (LEA) are common in elite athletes and typically arise from reduced energy intake, often involving some degree of carbohydrate (CHO) restriction. Whether the metabolic profile created by energy restriction per se is distinct compared to that driven by CHO restriction is unknown. Using untargeted metabolomics, we examined metabolic perturbations linked to CHO restriction and energy restriction in plasma from elite male endurance athletes. In a semi-randomized controlled trial, athletes (n = 20) completed one of three 5-day dietary interventions: high energy-high CHO (HCHO); LEA (energy-restricted, CHO-reduced); or low-CHO, high-fat (LCHF; energy-matched, CHO-restricted). Plasma samples were …

Harmonizing Neuropsychological Test Data Across Prospective Studies, Rosita Shishegar, James D. Doecke, Yen Ying Lim, Pierrick Bourgeat, Vincent Dore, Bhargav Tallapragada, Simon M. Laws, Tenielle Porter, Samantha Burnham, Azadeh Feizpour, Ashley Gillman, Michael Weiner, Jason Hassenstab, Christopher C. Rowe, Victor L. Villemagne, Colin L. Masters, Jurgen Fripp, Hamid Sohrabi, Paul Maruff

Research outputs 2022 to 2026

Introduction: Alzheimer's disease (AD) research relies on large datasets and advanced statistical models. However, individual population studies often lack sufficient sample size for conclusive results. Harmonizing cognitive test data across studies can address this gap, despite differences in testing protocols. This study harmonizes cognitive data from three major AD cohorts to support robust clinical–pathological modelling. Methods: Information from the Alzheimer's Disease Neuroimaging Initiative (N = 1446); Australian Imaging, Biomarkers and Lifestyle (N = 1764); and Open Access Series of Imaging Studies-3 (N = 440) were integrated, including cognitive scores, demographics, genetics, and clinical and neuroimaging data. Neuropsychological tests relevant to …

Seeg-Guided Responsive Neurostimulation To Treat Neocortical Epilepsy: A Multicenter Retrospective Study Of The Efficacy And Safety Of Depth Electrode-Mediated Neuromodulation, Sina Sadeghzadeh, Jon T Willie, Et Al.

2020-Current year OA Pubs

OBJECTIVES: Pivotal trials have established the effectiveness of the Responsive Neurostimulation System (RNS® System) in treating focal epilepsy. In clinical trials, depth leads were primarily used to treat mesial temporal seizure onsets while cortical strip leads were used to treat neocortical seizure onsets. Here, we systematically analyze the safety and efficacy of stereoelectroencephalography (sEEG)-guided depth leads to provide responsive stimulation to neocortical gray matter.

METHODS: Patients were stratified as strong responders (>median cohort seizure reduction %), weak responders (>0% and ≤median cohort seizure reduction %), and anti-responders (≤0%) based on percent seizure reduction at 1 year post-implant (1-Y). …

Association Of Sleep Disturbance With Survival After Colorectal Cancer Diagnosis: Results From The Colocare Study, Anita R Peoples, Adetunji T Toriola, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Sleep problems are common among cancer patients. The relationship between sleep disruption and clinical outcomes after colorectal cancer (CRC) diagnosis remains poorly understood. We investigated associations of sleep disruption with survival and recurrence in patients with CRC.

METHODS: CRC patients with stages I-IV (N = 895) were included in this study. Self-reported sleep disturbance was assessed presurgery using the sleep item from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core-30 and classified into "no/mild" or "moderate/severe" sleep disturbance. Cox-proportional hazard models were computed (HRs and 95% confidence intervals) to investigate associations of sleep disturbance …

A Systemic Selective Modified Mrna Delivery Platform For Preventing Chemotherapy-Induced Cardiotoxicity, Jimeen Yoo, Mengcheng Shen, Et Al.

2020-Current year OA Pubs

Doxorubicin (Dox) is a widely employed chemotherapeutic agent, but its use is clinically limited by dose-accumulative cardiotoxicity. More specifically, Dox induces oxidative stress and causes pro-apoptotic ceramide accumulation in cardiomyocytes (CMs). Acid ceramidase (AC) modified mRNA (modRNA) has been shown to reduce ceramide levels and protect the heart following ischemic injury; however, therapeutic modRNA applications have been hindered by the need for invasive delivery. Here, we present a platform for minimally intrusive transmission of modRNA to the heart. This CM-selective modRNA translational system (cmSMRTs) is encapsulated in lipid nanoparticles for intravenous (IV) delivery to enable systemic administration with high cardiac …

Sequence And Chemical Specificity Define The Functional Landscape Of Intrinsically Disordered Regions, Iris Langstein-Skora, Ryan J Emenecker, Alex S Holehouse, Et Al.

2020-Current year OA Pubs

Intrinsically disordered regions (IDRs) pervasively engage in essential molecular functions, yet they are often poorly conserved as assessed by sequence alignment. To explore the seeming paradox of how sequence variability is compatible with persistent function, we examined the functional determinants for a poorly conserved but essential IDR. We show that IDR function depends on two distinct but related properties: sequence and chemical specificity. Whereas sequence specificity operates via binding motifs and depends on the precise order and identity of residues, chemical specificity reflects the sequence-encoded chemistry of multivalent interactions across an IDR and depends on local and global chemical properties. …

Blood Dna Methylation-Predicted Plasma Protein Levels And Colorectal Cancer Survival, Alicia R Richards, Maria F Gomez, Bianca I Dowling, Esther Jean-Baptiste, Biljana Gigic, Jane C Figueiredo, Christopher I Li, David Shibata, Adetunji T Toriola, Doratha A Byrd, Cornelia M Ulrich, Paul A Stewart, Erin M Siegel, Jacob K Kresovich

2020-Current year OA Pubs

BACKGROUND: Protein EpiScores are a novel class of DNA methylation (DNAm)-based metrics proposed to measure peripheral immune system characteristics. Although Protein EpiScores have been associated with chronic disease risk, their relationship with colorectal cancer (CRC) survival has not been investigated.

METHODS: We generated new genome-wide DNAm data on pre-treatment whole blood samples from a case-control sample of 136 newly diagnosed CRC patients nested in the ColoCare Study and calculated 107 Protein EpiScores using the developer's algorithm. Over a median follow-up of 7.3 years (range: 0.3-13.8 years), 35 (26%) patients experienced disease recurrence, and 47 (35%) died. Protein EpiScore associations with …

Associations Of Child Amygdala Development With Borderline Personality Symptoms During Adolescence, Anna Constantino-Pettit, Kirsten Gilbert, Kiran Boone, Katherine Luking, Benjamin Geselowitz, Rebecca Tillman, Diana Whalen, Joan Luby, Deanna M Barch, Alecia Vogel

2020-Current year OA Pubs

BACKGROUND: The current understanding of the neural correlates of borderline personality disorder (BPD) is limited, but some evidence suggests that alterations in limbic structures play a role in adult BPD. The developmental course of structural neural differences in BPD is unknown. Whether there is specificity for structural alterations in BPD compared to other psychiatric presentations, such as major depressive disorder (MDD), remains unexplored. In the current study, we examined childhood trajectories of 2 limbic regions that have been implicated in BPD, hippocampal and amygdala volume, as they relate to adolescent BPD symptoms compared to MDD symptoms.

METHODS: Participants (n = …

Evaluation Of Host-Immune Biomarker Signatures As Multiplex Qpcr Diagnostic Assays: A Pilot Study Toward Meeting Who Target Product Profiles For Tb Diagnosis In India, Harriet N. Garlant, Kalaiarasan Ellappan, Noyal Mariya Joseph, Carrie Turner, Vishnukanth Govindaraj, Saka Vinod Kumar, Sanjeev Kumar, Seshadri S. Vasan, Karen Elizabeth Kempsell

Research outputs 2022 to 2026

Background: Tuberculosis (TB) remains the leading cause of death from a single infectious agent. Current diagnostic tools are limited, especially in low-resource settings. The World Health Organization's (WHO) Target Product Profiles (TPPs) call for rapid, non-sputum-based diagnostics with high sensitivity and specificity. This study evaluates our previously published TB-associated host-immune biomarkers alongside small-size signatures from other studies, in our previously published non-human primate (NHP) TB infection study dataset (GSE76703) and two previously published human datasets (GSE144127, GSE42834), which include other disease group comparators, including sarcoidosis. These were also evaluated in a small-scale, exploratory qPCR pilot study to assess the feasibility …

Comment On ‘Muscle-Specific Strength Better Predicts Physical Performance Decline Than Conventional Metrics: The I-Lan Longitudinal Aging Study’ By Chien Et Al., Ricardo M. Lima, Anthony J. Blazevich

Research outputs 2022 to 2026

No abstract provided.

Novel Small-Molecule Analogues Of Iu1 Ameliorate Amyloid-Β Mediated Toxicity In Alzheimer’S Disease Cell And Worm Models, Ajish Ariyath, Fraulein Denise Arigo, Izhar Wallach, W. M.A.D.Binosha Fernando, Ralph N. Martins, Prashant Bharadwaj

Research outputs 2022 to 2026

Dysregulation of the deubiquitinating enzyme Ubiquitin-specific peptidase 14 (USP14) is implicated in several neurodegenerative diseases, and IU1, an allosteric inhibitor, has shown neuroprotective effects by reducing protein aggregate toxicity. This study aimed to develop new IU1 analogues and evaluate their ability to mitigate amyloid-β (Aβ) accumulation and toxicity in Alzheimer’s disease (AD) cell and Caenorhabditis elegans worm models. IU1 and 71 newly designed analogues identified using the AtomNet^® virtual screening platform were assessed in an amyloid precursor protein-C terminal fragment/amyloid-β (APP-C99/Aβ)-producing AD cell model using a high-throughput toxicity assay. Lead compounds were further evaluated for their effects on neurodegeneration, …

Plasma Biomarker Progression Across The Alzheimer's Disease Amyloid Beta And Tau Positron Emission Tomography Trajectories, Rodrigo Cánovas, Christopher J. Fowler, Azadeh Feizpour, Vincent Dóre, Pierrick Bourgeat, Ziad S. Saad, Gallen Triana-Baltzer, Hartmuth C. Kolb, Manu Vandijck, Gwendlyn Kollmorgen, Clara Quijano-Rubio, Jurgen Fripp, Simon Laws, Anthony W. Bannon, Kaj Blennow, Henrik Zetterberg, Stephanie Rainey-Smith, Sulantha Mathotaarachchi, Christopher C. Rowe, Colin L. Masters, James D. Doecke

Research outputs 2022 to 2026

Introduction: With increased uptake in disease-modifying treatments for amyloid beta (Aβ) removal, it is important to measure performance of highly sensitive plasma biomarkers to detect the presence of Aβ and tau in cognitively impaired populations. Methods: In this study, we investigated a large set of plasma biomarkers for their capability to predict Aβ and tau positron emission tomography (PET) and their association with increasing Aβ and tau burden. RESULTS: From the biomarkers assessed, tau phosphorylated at threonine 217 (pTau217) showed the largest increases across the full range of Aβ and tau levels. Furthermore, pTau217/Aβ42 had the smallest proportion of participants …

Age And Sex Impact The Role Of Thrombospondin-2 And Thrombospondin-5 In Response To Hindlimb Ischemia, Irene Helenowski, Ashley Peters, Melissa Rangel, Corinne Bunn Md, Xuerong Wang, Kristopher Maier, Vivian Gahtan

Biostatistics Collaborative Core: Faculty Publications and Other Works

Peripheral arterial disease progression to critical limb ischemia remains a significant burden in the aged, necessitating revascularization. Therapies to enhance neovascularization, such as angiogenesis or arteriogenesis, may provide an option for patients not suitable for surgery. The thrombospondins (TSPs) are secreted matricellular glycoproteins, with TSP-1, TSP-2, and TSP-5 implicated in neovascularization. Currently, there is little data regarding the effects of TSP-2, TSP-5, sex, and aging on angiogenesis and arteriogenesis. In vitro, the effect of TSP-2 or TSP-5 on early or late passage endothelial cell (EC) tubule formation or disruption was assessed. In vivo, angiogenesis, and arteriogenesis in male and female, …

Monosaccharide Binding To Synthetic Carbohydrate Receptor Microarrays, Milan A. Shlain

Dissertations, Theses, and Capstone Projects

Chapter 1: A glycan detection platform comprised of synthetic carbohydrate receptors (SCRs) immobilized onto polymer brushes was prepared. SCR043, an alkene-containing SCR, was incorporated into grafted-from polymer brushes using hypersurface photolithography, resulting in microarrays of SCR043-functionalized polymer brushes, where brush height (h) and SCR grafting density (Γ) is controlled precisely at each feature in the array. The influence of h and Γ on the binding to five fluorescently labelled monosaccharides – α-glucose (α-Gluc-FL), α-galactose (α-Gal-FL), α-mannose (α-Man-FL), β-glucose (β-Gluc-FL), and β-galactose (β-Gal-FL) – in aqueous buffer …

Protein Allostery Probed By Ligands Across Sites, Virgil A. Woods

Dissertations, Theses, and Capstone Projects

Allostery is a pervasive regulatory principle throughout biology, yet the structural pathways by which distal inputs alter active‑site chemistry within protein structures remain incompletely defined and exploited. This dissertation uses protein tyrosine phosphatase 1B (PTP1B) as a tractable model to map those pathways with complementary experimental and computational tools. I integrate high‑resolution hydrogen-deuterium exchange mass spectrometry (HDX-MS), room-temperature crystallography, NMR, steady-state kinetics, crystallographic pseudo-ensembles, and machine-learning-guided ligand discovery. The working premise is that regulation reflects redistribution within a conformational ensemble rather than a binary switch. That orthogonal perturbations by small molecules, mutations, and protein partners can be used to both …

Ischemic Stroke As The Initial Presentation Of Advanced Pancreatic Adenocarcinoma: A Case Of Marantic Endocarditis., Micah Harris

Ambulatory and Primary Care Articles

Nonbacterial thrombotic endocarditis (NBTE), formerly known as marantic endocarditis, is a rare condition characterized by sterile vegetations on cardiac valves and is often associated with hypercoagulable states such as adenocarcinoma. We describe a patient who presented with multiple embolic cerebrovascular accidents, ultimately found to be secondary to NBTE, which served as the initial manifestation of previously undiagnosed advanced pancreatic adenocarcinoma. This case underscores the importance of considering NBTE in patients with multifocal embolic infarcts, particularly when blood cultures are negative, echocardiography reveals valvular abnormalities without evidence of infection, and clinical suspicion for an underlying malignancy is present.

Transcriptomics And Metabolomics Analysis Reveal Cell Subpopulations Of Trophoblast Cells Associated With Preeclampsia, Xiaojun Zhu, Ying Jiang, Lilin Wang, Peiyue Jiang, Zixing Zhong, Hetong Li, Caihong Zheng, Lujiao Chen, Juan Wei, Xishi Lin, Peng Ding, Zehua Dong, Xiaosheng Wang, Qiong Luo

Faculty, Staff and Student Publications

Placental abnormalities are central to preeclampsia (PE), yet the cellular and molecular mechanisms underlying this dysfunction remain unclear. We applied a multi-layered, integrative approach to investigate placental tissue from patients with PE and matched controls. Single-cell RNA sequencing (scRNA-seq; GSE173193) and bulk RNA sequencing (bulk RNA-seq; GSE203507) datasets were obtained from the Gene Expression Omnibus. The scRNA-seq dataset included two PE and two control samples, whereas the bulk RNA-seq dataset focused on eight early-onset PE and five uncomplicated term births. Trophoblast subpopulations were identified via scRNA-seq, and pseudotime analysis was used to trace differentiation trajectories. Differential expression and pathway enrichment …