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Long Acting Beta2-Adrenergic Receptor Agonists Reverse Diabetic Nephropathy And Liver Steatosis In Murine Models Of Diabetes And Are Associated With Protection In Retrospective Human Studies, Brennan Winkler Jan 2026

Long Acting Beta2-Adrenergic Receptor Agonists Reverse Diabetic Nephropathy And Liver Steatosis In Murine Models Of Diabetes And Are Associated With Protection In Retrospective Human Studies, Brennan Winkler

MUSC Theses and Dissertations

Diabetes Mellitus (DM) affects 13.9% of men and 14.3% of women worldwide, a total of approximately 828 million people. Patients with diabetes are at risk of several complications including diabetic nephropathy (DN) and metabolic-associated steatohepatitis (MASH). These diseases eventually lead to end stage kidney disease (ESKD) and liver failure requiring dialysis and organ transplantation. In addition, diabetes exacerbates disease severity of autosomal dominant polycystic kidney disease (ADPKD), the most common potentially lethal genetic disease to affect humans with a prevalence of 1 in 500-1000. Therefore, a therapeutic approach that can attenuate organ damage and restore function in patients with DM, …


Sexually Dimorphic Effects Of Gpnmb Modulation On Vertebral Bone Mass Regulation And Intravertebral Disc Health, Hakem Altawil, Fayez Safadi Jan 2026

Sexually Dimorphic Effects Of Gpnmb Modulation On Vertebral Bone Mass Regulation And Intravertebral Disc Health, Hakem Altawil, Fayez Safadi

Williams Honors College, Honors Research Projects

Osteoporosis and vertebral degeneration are major contributors to musculoskeletal morbidity, yet the molecular mechanisms regulating vertebral bone and intervertebral disc (IVD) homeostasis remain incompletely understood. GPNMB (osteoactivin) has been identified as a regulator of bone remodeling, though its role in spine health is unclear. This study evaluated the effects of GPNMB deficiency on lumbar vertebral bone microarchitecture and IVD integrity in a sex-dependent context.

Six-month-old male and female wild-type (WT) and GPNMB knockout (KO) mice were analyzed using micro–computed tomography (µCT) of lumbar vertebrae (L4–L6) and histological assessment of the L5–L6 IVD. KO males exhibited increased bone volume fraction, bone …


Metabolic Syndrome Beyond Diagnostic Criteria: Population-Scale Integrative Metabolomics Characterization, Marwa Talal Jan 2026

Metabolic Syndrome Beyond Diagnostic Criteria: Population-Scale Integrative Metabolomics Characterization, Marwa Talal

Theses and Dissertations

Background: Metabolic syndrome (MetS) is a complex cluster of interrelated metabolic abnormalities associated with elevated cardiometabolic risk. While diagnosis is based on well-established five clinical criteria, these may overlook early or atypical metabolic alterations. Large-scale metabolomic profiling offers an opportunity to identify biochemical signatures of MetS beyond diagnostic bias and to evaluate their relative importance across different presentations of the syndrome.

Methods: Data from 117,147 UK Biobank participants were analyzed in a cross-sectional design. High-throughput NMR quantified 75 circulating metabolites, for. Univariate analyses, MetS subtype stratification, and elastic net models with SHAP interpretation were applied to assess feature …


The Role Of Mscs In The Il23/17 Pathway And Their Response To Mechanical Stress, Norma Aileen Dominguez Jimenez Jan 2026

The Role Of Mscs In The Il23/17 Pathway And Their Response To Mechanical Stress, Norma Aileen Dominguez Jimenez

Honors Theses

Mechanical stress plays a central role in shaping cellular behavior within skeletal tissues. At the enthesis, where tendons and ligaments attach to bone, repeated mechanical loading is strongly associated with inflammation and the development of ankylosing spondylitis (AS). Although mesenchymal stem cells (MSCs) are known to contribute to tissue structure and repair at these sites, their potential role in inflammatory signaling, particularly within the I 23/IL 17 pathway, remains unclear. In this thesis I investigated whether MSCs are capable of expressing cytokines involved in this pathway and how mechanical stress and differentiation influence this expression. Using the mouse derived C3H/10T1/2 …


Effect Of Biodentine And Treated Dentine Matrix On Viability And Proliferation Of Human Dental Pulp Stem Cells, Nada Barakat, Rana El-Qashty, Mohamad E. Helal Jan 2026

Effect Of Biodentine And Treated Dentine Matrix On Viability And Proliferation Of Human Dental Pulp Stem Cells, Nada Barakat, Rana El-Qashty, Mohamad E. Helal

Mansoura Journal of Dentistry

Objective: The present study aimed to assess the dose-dependent effect of Biodentine (BD) and human-treated dentin matrix (hTDM) on the proliferation of human dental pulp stem cells (hDPSCs).

Materials and methods: hTDM was prepared and characterized. The concentration of proteins released from BD and hTDM extracts were quantified using the bicinchoninic acid (BCA) assay after 3 and 7 days. hDPSCs were successfully isolated and characterized, then treated with various concentrations of BD extracts (20, 2, and 0.2 mg/mL) and hTDM extracts (100%, 80%, 60%, 40%, 20%, and 10%). Cell viability was determined after 7 days of incubation using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium …


An Attempt For In Situ Bio-Root Regeneration By Using Treated Dentin Matrix And Dental Pulp Stem Cells In Albino Rats, Amani Mohamad, Ahmad A. Emam, Eman Hany, Mohamed Abdulrahman Jan 2026

An Attempt For In Situ Bio-Root Regeneration By Using Treated Dentin Matrix And Dental Pulp Stem Cells In Albino Rats, Amani Mohamad, Ahmad A. Emam, Eman Hany, Mohamed Abdulrahman

Mansoura Journal of Dentistry

Objectives: This study was conducted to prepare and characterize root-shaped treated dentin matrix (TDM) scaffolds, and to evaluate their efficacy together with seeded dental pulp stem cells (DPSCs) as potential bio-roots in extraction sockets of rat models.

Materials and Methods: Root-shaped TDM specimens were prepared and characterized. Following extraction of maxillary incisors, the alveolar sockets were implanted with TDM segments measuring 8 mm in length, either alone (TDM group) or seeded with dental pulp stem cells (TDM/DPSCs group). Animals were euthanized at two and six weeks post-implantation, specimens were processed for histological, histochemical and immunohistochemical analyses.

Results: TDM group at …


Chronic Alcohol Consumption Reprograms Osteoclast Lineage Communications To Promote Osteoclastogenesis, Hami Hemati, Brianna M. Doratt, Ilhem Messaoudi Jan 2026

Chronic Alcohol Consumption Reprograms Osteoclast Lineage Communications To Promote Osteoclastogenesis, Hami Hemati, Brianna M. Doratt, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chronic alcohol consumption increases the risk of osteoporosis and fracture by disrupting bone remodeling, in part by enhancing osteoclastogenesis. However, the cellular mechanisms underlying this process remain incompletely defined. We analyzed scRNA-seq data from osteoclasts differentiated in vitro from bone marrow mononuclear cells obtained from macaques following 12 months of chronic ethanol or isocaloric control solution consumption. Module scoring, trajectory inference with generalized additive modeling (tradeSeq), and CellChat-based analyses of intercellular communication were applied to uncover ethanol-induced changes in metabolic reprogramming, lineage progression, and signaling network dynamics. Module scoring indicated metabolic reprogramming toward oxidative phosphorylation, with reduced glycolytic, migratory, and …


Alcohol Consumption Exacerbates High-Fat Diet- Mediated Disruptions In Myelopoiesis And Osteoclastogenesis In Mouse Models Of Metabolic Dysfunction-Associated Liver Diseases, Hami Hemati, Madison B. Blanton, Lauren Rutt, Nicholas Keiran, Rebecca Geron, Florence Lima, Rebecca L. Mccullough, Ilhem Messaoudi Jan 2026

Alcohol Consumption Exacerbates High-Fat Diet- Mediated Disruptions In Myelopoiesis And Osteoclastogenesis In Mouse Models Of Metabolic Dysfunction-Associated Liver Diseases, Hami Hemati, Madison B. Blanton, Lauren Rutt, Nicholas Keiran, Rebecca Geron, Florence Lima, Rebecca L. Mccullough, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Objective: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Alcohol-related Liver Disease (MetALD) exhibit systemic immune abnormalities. Given that such immune dysregulation is closely linked to the skeletal complications frequently observed in MASLD and MetALD, we sought to comprehensively characterize the bone marrow hematopoietic compartment and its link to osteoclastogenesis.

Methods: We utilized bone marrow from mouse models of MASLD (high-fat diet, HFD) and MetALD (high-fat diet plus ethanol, HFD+EtOH), followed by flow cytometric analysis to phenotype hematopoietic stem and progenitor cells (HSPCs), as well as in vitro and in vivo assays to evaluate osteoclastogenesis.

Results: We found that …


Characterizing Immune Perturbations In Peripheral Blood Following The East Palestine, Ohio Train Derailment, Sheridan B. Wagner, Hami Hemati, Siva Gandhapudi, Timothy J. Hilbert, Candace J. Brancato, Erin N. Haynes, Ilhem Messaoudi Jan 2026

Characterizing Immune Perturbations In Peripheral Blood Following The East Palestine, Ohio Train Derailment, Sheridan B. Wagner, Hami Hemati, Siva Gandhapudi, Timothy J. Hilbert, Candace J. Brancato, Erin N. Haynes, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: The East Palestine, Ohio, train derailment on February 3rd, 2023, resulted in the exposure of residents and the surrounding area to numerous hazardous chemicals, which included known acute irritants and human carcinogens. Despite evacuation and cleanup, both residents and responders reported high occurrences of symptoms associated with exposure in the months following, such as eye, skin, and respiratory irritation, headaches, and fatigue. The long-term health consequences for residents remain uncertain.

Objective: To assess the potential for immune perturbations resulting from the exposure, we performed a broad investigation of circulating immune cells and mediators from residents of East Palestine, OH, …


Combinatorial Immunotherapy Drives Exhaustion In Tumor Antigen–Specific Cd8+ T Cells Within The Mouse Renal Tumor Microenvironment, Holly R. Stephens, Elizabeth Elkins, Jing Li, Zoey N. Swalley, Henry Nnaemeka Ogbonna, Pia Muri, Zachary Roberts, Francesca R. Dempsey, Md Akkas Ali, Md Hasanul Banna Siam, Richard Kirkman, Jianqing Zhang, Sunil Sudarshan, Daniel J. Tyrrell, Hubert M. Tse, Daniel L. Smith Jr, Lyse A. Norian Jan 2026

Combinatorial Immunotherapy Drives Exhaustion In Tumor Antigen–Specific Cd8+ T Cells Within The Mouse Renal Tumor Microenvironment, Holly R. Stephens, Elizabeth Elkins, Jing Li, Zoey N. Swalley, Henry Nnaemeka Ogbonna, Pia Muri, Zachary Roberts, Francesca R. Dempsey, Md Akkas Ali, Md Hasanul Banna Siam, Richard Kirkman, Jianqing Zhang, Sunil Sudarshan, Daniel J. Tyrrell, Hubert M. Tse, Daniel L. Smith Jr, Lyse A. Norian

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Immunotherapies have greatly improved outcomes for patients with renal cell carcinoma (RCC), yet response rates remain suboptimal and the factors promoting therapy resistance versus sensitivity are incompletely understood. Currently, no preclinical model of orthotopic renal cancer exists that permits evaluation of tumor antigen–specific (TAS) CD8+ tumor-infiltrating lymphocytes (TILs). To address this deficiency, we developed a mouse renal cancer model that permits tracking of adoptively transferred TAS CD8+ T cells. Renca-LUC tumor cells were transduced to express tumor ERK (tERK), a model antigen expressing a one-amino-acid change from wild-type ERK, resulting in recognition by tERK/H-2Kd-specific DUC Thy1.1 …


Ventilation-Perfusion Scan: A Functional Imaging Approach To Regional Lung Disease In Primary Ciliary Dyskinesia, Gabriel Román-Ríos, Gabriel Rosario-Ortiz, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas Jan 2026

Ventilation-Perfusion Scan: A Functional Imaging Approach To Regional Lung Disease In Primary Ciliary Dyskinesia, Gabriel Román-Ríos, Gabriel Rosario-Ortiz, Marcos J Ramos-Benitez, Ricardo A Mosquera, Wilfredo De Jesús-Rojas

Faculty, Staff and Student Publications

Introduction: As a rare genetic disorder defined by defective ciliary motility, Primary Ciliary Dyskinesia (PCD) leads to chronic respiratory complications. A founder variant in the RSPH4A [c.921+3_921+6delAAGT] gene, common in Puerto Rico, impairs ciliary function and contributes to progressive lung disease. Today, the clinical value of ventilation/perfusion (V/Q) scans in PCD has not been thoroughly investigated as well as pulmonary function tests (PFTs) and chest imaging. To explore the role and clinical utility of V/Q scans in PCD.

Methods: Retrospective evaluation of pulmonary function tests, chest imaging, and Tc-99m DTPA ventilation and Tc-99m MAA perfusion scans in ten patients with …


Exploring Biopsychosocial Influences On Hookup Culture And Disrupting Compulsory Behaviors In Emerging Adults: A Multidisciplinary Analysis Of A Contemporary Public Health Concern, Catherine Benjamin Jan 2026

Exploring Biopsychosocial Influences On Hookup Culture And Disrupting Compulsory Behaviors In Emerging Adults: A Multidisciplinary Analysis Of A Contemporary Public Health Concern, Catherine Benjamin

Honors Theses and Capstones

Multidisciplinary analysis, including biology, psychology, and sociology, to better understand the compulsory Hookup Culture that exists as a contemporary public health concern among the age group defined as emerging adults. Sexually Transmitted Infections (STIs) diagnoses are steadily rising in the United States and disproportionately affecting college students. Early socialization and current educational resources that contribute to shame and stigma are discussed to explain how lifestyle and social conditions can act as risk factors for individual health outcomes.


Tick Lipocalin Triggers Mammalian Igfbp-3-Mediated Apoptosis In Macrophages And Keratinocytes, Krittika Nandy, P. P. Mahesh, Lichao Liu, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta Jan 2026

Tick Lipocalin Triggers Mammalian Igfbp-3-Mediated Apoptosis In Macrophages And Keratinocytes, Krittika Nandy, P. P. Mahesh, Lichao Liu, Daniel E. Sonenshine, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ticks secrete several molecules, including lipocalins, in their saliva during blood feeding on a vertebrate host. In this study, we provide novel evidence on the role of Ornithodoros turicata americanus tick lipocalin (Otlip) in modulating cytokine expression and in triggering apoptosis in mammalian macrophages and keratinocytes. The cytokine array analysis revealed significantly increased secretion of insulin-like growth factor-binding protein 3 (IGFBP3) from murine macrophage cell line upon treatment with recombinant Otlip protein (rGST-Otlip) when compared to the secretion noted from cells treated with a control protein (rGST). Similar observation with cytokine protein array analysis was noted when murine macrophages were …


Anatomical Atlas Of Kinase Responsiveness To Weight Gain: Adipose Depot Reprogramming In Diet-Induced Adiposity, Wang-Hsin Lee, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Mei Xu, Terry D. Hinds, Jr. Jan 2026

Anatomical Atlas Of Kinase Responsiveness To Weight Gain: Adipose Depot Reprogramming In Diet-Induced Adiposity, Wang-Hsin Lee, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Mei Xu, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

Background/Objectives: Adipose tissue depots located at different anatomical sites exert differential functions in response to adiposity and glucose intolerance. These fat depots exhibit distinct metabolic signaling patterns that may influence pathological fat accumulation, thereby affecting the efficacy of anti-obesity interventions. Nonetheless, the mechanisms underpinning depot-specific signaling and pathway responsiveness remain insufficiently understood.

Methods: Kinase activity was characterized during the progression of adiposity across five adipose tissue depots in obese versus lean mice using the advanced PamGene kinome technology. Furthermore, kinase pathways in human preadipocytes and mouse 3T3-L1 preadipocytes were analyzed and compared with those in their differentiated, mature adipocytes. The …


A Narrative Review Of The High-Carbohydrate Fueling Revolution (≥100 G/H) In The Professional Peloton, Patrick B. Wilson Jan 2026

A Narrative Review Of The High-Carbohydrate Fueling Revolution (≥100 G/H) In The Professional Peloton, Patrick B. Wilson

Exercise Science Faculty Publications

High-carbohydrate fueling in cycling (defined as ≥ 100 g/h for this paper) has received significant media attention in recent years. Whether this practice improves performance, however, remains an unresolved issue in the scientific literature. The purpose of this narrative review is to provide an up-to-date analysis of the practice of high-carbohydrate fueling, with a specific focus on potential performance implications in professional cycling. Topics covered include historical carbohydrate intake guidelines, research directly comparing high-carbohydrate fueling with traditional fueling guidelines, theorized benefits of high-carbohydrate fueling specific to cycling, potential risks associated with high-carbohydrate fueling, and personalizing carbohydrate intakes. Among a small …


Granulomatous Cellular Signatures In Nontuberculous And Tuberculous Mycobacterial Infections, Brianna M. Doratt, Ethan G. Napier, Mahdi Eskandarian Boroujeni, Sarah Douglas, Michael H. Davies, Luiz Bermudez, Eliot Spindel, Erin F. Mccaffrey, Ilhem Messaoudi Jan 2026

Granulomatous Cellular Signatures In Nontuberculous And Tuberculous Mycobacterial Infections, Brianna M. Doratt, Ethan G. Napier, Mahdi Eskandarian Boroujeni, Sarah Douglas, Michael H. Davies, Luiz Bermudez, Eliot Spindel, Erin F. Mccaffrey, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Mycobacterium tuberculosis (Mtb) and nontuberculous mycobacteria (NTM) are acid-fast bacilli that trigger granuloma formation, a hallmark immune response aimed at containing infection. While the biology of Mtb granulomas has been widely investigated, far less is known about granulomas caused by NTM infection, despite the increasing prevalence and clinical challenge of NTM cases worldwide. Because granulomas influence infection control, pathology, and treatment response, understanding their cellular organization and signaling is critical to improving therapeutic strategies. Therefore, we characterized granulomas formed following infection of rhesus macaques with Mycobacterium avium subsp. hominissuis (MAH) and compared them to granulomas from cynomolgus macaques infected with …


The Influence, Dependency, And Targeting Of Fatty Acid Uptake In Er+ Breast Cancer, Abigail E. Goen Jan 2026

The Influence, Dependency, And Targeting Of Fatty Acid Uptake In Er+ Breast Cancer, Abigail E. Goen

Dartmouth College Ph.D Dissertations

Estrogen Receptor-positive/ Human Epidermal Growth Factor 2-negative, breast cancer (ER+/HER2- BC) is the most prevalent subtype of BC, impacting millions of individuals. Although early screening and treatment with endocrine therapy has greatly enhanced survival, this subtype sustains a steady increase of risk for recurrent disease for decades after diagnosis, indicating the persistence of residual cancer cells that are capable of maintaining dormancy for >20 years prior to metastatic outgrowth. Dormant cells reprogram metabolic pathways which can be profoundly influenced by the tumor microenvironment in promoting quiescence or proliferation. Fatty acid oxidation dependency has been noted as a hallmark of drug …


Photobiomodulation Mitigates The Inhibitory Effects Of Pirfenidone On Cancer-Associated Fibroblasts And Their Pro-Tumorigenic Properties: A Cause For Concern, Nima Rastegar-Pouyani, Alireza Nasirpour, Fatemeh Javani Jouni, Hossein Vazini, Ahmad Moshaii Jan 2026

Photobiomodulation Mitigates The Inhibitory Effects Of Pirfenidone On Cancer-Associated Fibroblasts And Their Pro-Tumorigenic Properties: A Cause For Concern, Nima Rastegar-Pouyani, Alireza Nasirpour, Fatemeh Javani Jouni, Hossein Vazini, Ahmad Moshaii

Electrical & Computer Engineering Faculty Publications

Cancer-associated fibroblasts (CAFs) within the tumor microenvironment highly contribute to cancer progression and poor prognosis. Recent findings introduce pirfenidone, a medication for pulmonary fibrosis, as a promising repurposed candidate for inhibiting CAFs. Moreover, photobiomodulation (PBM), or low-level laser therapy, has surfaced as a potential modality against cancer; however, its impact on CAFs is not thoroughly comprehended. The present study scrutinized the effects of PBM, pirfenidone, and PBM+pirfenidone on CAFs, and their consequent impact on cancer cells using the CAF-conditioned media. After treating CAFs with PBM at wavelengths 660 and 980 nm with/without PFD and then culturing cancer cells in the …


Flexible Cu Nanostructured Laser-Induced Graphene Electrodes For Highly Sensitive And Non-Invasive Lactate Detection In Saliva, Anju Joshi, Gymama Slaughter Jan 2026

Flexible Cu Nanostructured Laser-Induced Graphene Electrodes For Highly Sensitive And Non-Invasive Lactate Detection In Saliva, Anju Joshi, Gymama Slaughter

Center for Bioelectronics Publications

A scalable and facile fabrication strategy is presented for developing a flexible, nanostructured, non-enzymatic electrochemical sensor for lactate detection based on copper-modified laser-induced graphene (CuNPs/LIG). A one-step electrodeposition process was employed to uniformly decorate the porous LIG framework with copper nanostructures, offering a cost-effective and reproducible approach for constructing enzyme-free sensing platforms. Scanning electron microscopy and energy-dispersive X-ray spectroscopy confirmed dense Cu nanostructure loading and efficient interfacial integration across the conductive LIG surface. The resulting CuNPs/LIG electrode exhibited excellent electrocatalytic performance, achieving a sensitivity of 8.56 μA µM−¹ cm−² with a low detection limit of 42.65 …


The Effects Of Stress-Related Hormones On Excitatory Synapse Formation, Autumn C. Garvey Jan 2026

The Effects Of Stress-Related Hormones On Excitatory Synapse Formation, Autumn C. Garvey

Honors Undergraduate Theses

Stress profoundly influences brain function through neuromodulatory hormones that regulate synaptic plasticity, yet how temporal patterns of hormone exposure shape excitatory synapse formation remains poorly understood. This study investigates how exposure to stress hormones, norepinephrine and cortisol, affects excitatory synapse development. While existing research primarily compares concentration models, real-world stress occurs in variable patterns that may produce distinct neural outcomes. To address this gap, differentiated Neuro2A neuronal cells are exposed to norepinephrine or cortisol under a continuous treatment paradigm designed to model chronic stress conditions. Following treatment, immunofluorescence imaging is utilized to quantify excitatory synapse formation through analysis of presynaptic …


Manuka Honey Modulates Oxidative Stress In Neuro2-A Cells Through Mitochondrial Regulation, Rachel Abramovici Jan 2026

Manuka Honey Modulates Oxidative Stress In Neuro2-A Cells Through Mitochondrial Regulation, Rachel Abramovici

Honors Undergraduate Theses

Manuka honey is known for its vital usage in wound healing, being an agonist towards fighting infections, and is an acting antioxidant [32]. Its main constituents are flavonoids and phenolic compounds, with methyl syringate (MSYR) being a major active ingredient. The specific compounds responsible for these antioxidant effects, particularly in the CNS, remain unclear. It is hypothesized that pre-treatment of mouse neuroblastoma cells with MSYR followed by hydrogen peroxide exposure will activate the AMPK/SIRT1/PGC-1a pathway, due to MSYR’s phenolic structure, and thus reduce oxidative stress and improve mitochondrial biogenesis. Hydrogen peroxide is a standard reactive oxygen species (ROS) treatment to …


Impact Of Senescence On Breast Cancer Outcomes, Gracie Sous Jan 2026

Impact Of Senescence On Breast Cancer Outcomes, Gracie Sous

Honors Undergraduate Theses

Cellular senescence is a biological process in which damaged cells exit the cell cycle while remaining metabolically active and accumulating within tissues. Senescence plays a complex role in breast cancer progression, largely through the secretion of senescence-associated secretory phenotype (SASP) factors. These factors include a broad range of inflammatory cytokines, chemokines, and signaling molecules that can influence the tumor microenvironment.

Studies suggest that senescence may significantly promote cancer metastasis. Therefore, this study aims to investigate the genes involved in cancer progression and to improve understanding of how SASP is regulated, which is critical for improving breast cancer outcomes. The central …


Rac1 Gtpase Regulates The Scfβtrcp-Mediated Degradation Of Claspin And The Cellular Response Of Pancreatic Cancer Cells To Gamma Rays, Neha Chaudhary, Tabbatha N. Somers, Surinder K. Batra, Ying Yan, Michel M. Ouellette Jan 2026

Rac1 Gtpase Regulates The Scfβtrcp-Mediated Degradation Of Claspin And The Cellular Response Of Pancreatic Cancer Cells To Gamma Rays, Neha Chaudhary, Tabbatha N. Somers, Surinder K. Batra, Ying Yan, Michel M. Ouellette

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND/OBJECTIVES: Pancreatic ductal adenocarcinomas (PDACs) are lethal tumors exhibiting resistance to most cancer therapeutics, particularly DNA-damaging agents. The

METHODS: Western blot analyses were used to assess the impacts of Rac1 inhibition on the components of the ATR/Chk1 cascade.

RESULTS: Here, we show that Rac1 inhibition disrupts ATR/Chk1 signaling by promoting degradation of Claspin, a key component of the fork protection complex needed for the Ser345-phosphorylation of Chk1 by ATR. In PDACs and normal pancreatic ductal cells, Rac1 inhibition (via inhibitors or siRNA) decreased Claspin protein levels without affecting its mRNA, reflecting a >3-fold reduction in Claspin's half-life. Claspin contains a …


Mucin 5ac Modulates Cancer-Associated Fibroblast Heterogeneity Through Epigenetic Reprogramming Of Precursor Cells, Rachel J. Kehrberg, Namita Bhyravbhatla, Zahraa Wajih Alsafwani, Xiaoqi Li, Gopalakrishnan Natarajan, Imran Khan, Randall E. Brand, Maneesh Jain, Surinder K. Batra, Sushil Kumar Jan 2026

Mucin 5ac Modulates Cancer-Associated Fibroblast Heterogeneity Through Epigenetic Reprogramming Of Precursor Cells, Rachel J. Kehrberg, Namita Bhyravbhatla, Zahraa Wajih Alsafwani, Xiaoqi Li, Gopalakrishnan Natarajan, Imran Khan, Randall E. Brand, Maneesh Jain, Surinder K. Batra, Sushil Kumar

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer (PC) is characterized by extensive desmoplasia, with heterogeneous cancer-associated fibroblasts (CAFs) as a major component. However, the contribution of distinct precursor cells to CAF heterogeneity remains poorly defined. This study investigated the role of Muc5ac in modulating CAF heterogeneity by maturing precursor cells, including adipose-derived mesenchymal stem cells (AD-MSCs), bone marrow-derived MSCs (BM-MSCs), and pancreatic stellate cells (PSCs), into different CAF subsets. RNA sequencing of precursor cells treated with conditioned media from Muc5ac-proficient or -deficient cancer cells revealed distinct transcriptional profiles. Muc5ac significantly modulated the expression of Dnmts and Tets in AD-MSCs, promoting the acquisition of extracellular matrix …


35 Individuals With Huwe1-Related Neurodevelopmental Disorder And Suggested Clinical Evaluations, Mindy H. Li, Deziree L. Coleman, Kelsey Hogan, Danielle Luz, Lindsay Bhandari, Newell Belnap, Tiffany Busa, Charles Coutton, Klaus Dieterich, Svetlana Gorokhova, Clara Hildebrandt, Rachel Logan, Milena Mariani, Manuela Morleo, Vincenzo Nigro, John Pappas, Rachel Rabin, Kelly Schoch, Angelo Selicorni, Vandana Shashi, Rebecca Spillman, Jennifer Sullivan, Charlotte Tardy, Samantha A. Schrier Vergano, Brock Grill, Kristin Baranano Jan 2026

35 Individuals With Huwe1-Related Neurodevelopmental Disorder And Suggested Clinical Evaluations, Mindy H. Li, Deziree L. Coleman, Kelsey Hogan, Danielle Luz, Lindsay Bhandari, Newell Belnap, Tiffany Busa, Charles Coutton, Klaus Dieterich, Svetlana Gorokhova, Clara Hildebrandt, Rachel Logan, Milena Mariani, Manuela Morleo, Vincenzo Nigro, John Pappas, Rachel Rabin, Kelly Schoch, Angelo Selicorni, Vandana Shashi, Rebecca Spillman, Jennifer Sullivan, Charlotte Tardy, Samantha A. Schrier Vergano, Brock Grill, Kristin Baranano

Department of Pediatrics Faculty Publications

HUWE1 (HECT, UBA, and WWE Domain Containing E3 Ubiquitin Protein Ligase1, OMIM 300697), located at Xp11.22, encodes a ubiquitin ligase that is highly conserved across species. Genetic variants in HUWE1 described in multiple independent studies cause X-linked intellectual disability, including in the patients identified by Juberg, Marsidi, and Brooks. This report describes 35 additional cases of individuals with variants in HUWE1 and suggested guidelines for clinical management. Our study includes several female cases, which have not been widely reported previously. Our findings confirm earlier reported clinical features including developmental delay, autism, hypotonia, short stature, and dysmorphic facial features as well …


Stat4-Dependent Regulation Of Neuroinflammation In Atherosclerosis, Natalie Stahr, Alina K. Moriarty, Shelby D. Ma, W. Coles Keeter, Woong-Ki Kim, Larry D. Sanford, Elena V. Galkina Jan 2026

Stat4-Dependent Regulation Of Neuroinflammation In Atherosclerosis, Natalie Stahr, Alina K. Moriarty, Shelby D. Ma, W. Coles Keeter, Woong-Ki Kim, Larry D. Sanford, Elena V. Galkina

Department of Biomedical and Translational Sciences Faculty Publications

Atherosclerosis is linked to an increased risk of cognitive decline, with chronic inflammation being a common feature of both pathologies. IL-12 activates STAT4 to regulate myeloid cell functions, and blockade of this pathway alleviates cognitive impairment in Alzheimer's models. However, the mechanisms connecting vascular pathology to neuroinflammation remain unclear. Here, we examine whether STAT4 functions as a common mediator of neuroinflammation in atherosclerosis. We demonstrate that LysMCre-specific STAT4 deficiency ameliorates deficits in long-term memory in low-density lipoprotein-deficient (Ldlr-/-) mice fed a high-fat diet (HFD-C). STAT4 deficiency moderately reduces Ser199-phosphorylated Tau burden. Atherosclerosis alters brain immune …


Revised Microbiology Core Knowledge Objectives For Modern Undergraduate Medical Education, Timothy J. Bauler, Cindy G. Arvidson, Samina Akbar, Dennis N. Arvidson, Margaret E. Bauer, Dwayne M. Baxa, Rebecca J. Greenblatt, Kerstin Honer Zu Bentrup, Yingguang Liu, Inaia Phoenix, Julie A. Kerry Jan 2026

Revised Microbiology Core Knowledge Objectives For Modern Undergraduate Medical Education, Timothy J. Bauler, Cindy G. Arvidson, Samina Akbar, Dennis N. Arvidson, Margaret E. Bauer, Dwayne M. Baxa, Rebecca J. Greenblatt, Kerstin Honer Zu Bentrup, Yingguang Liu, Inaia Phoenix, Julie A. Kerry

Department of Biomedical and Translational Sciences Faculty Publications

Defining the core content for each scientific discipline in a modern preclinical medical education curriculum is critical to ensure optimal student learning and application of foundational knowledge for clinical practice. Attendees of the Association of Medical School Microbiology and Immunology Chairs (AMSMIC) Educational Strategies Workshop recently highlighted the need for updated medical microbiology learning objectives, given the shift in medical education toward less time for preclinical coursework and more integrated learning. Herein, we describe the process of developing a comprehensive, educator-driven set of knowledge objectives for medical microbiology. These objectives emphasize common pathogens, as well as pathogens associated with severe …


Distinct Glycosyltransferase Expression Governs Organ-Specific Survival In Pancreatic Cancer Metastasis, Venkatesh Varadharaj, Frank Leon, Nivedeta Krishna Kumar, Palanisamy Nallasamy, Pratima Raut, Annant Bir Kaur, Kirtana Arikath, Wyatt Petersen, Sanchita Rauth, Neelanjana Gayen, Zahraa Wajih Alsafwani, Poompozhil Mathivanan, Saravanakumar Marimuthu, Kavita Mallya, Madhu Bommideni, Jesse L. Cox, G. Talmon, Paul M. Grandgenett, Michael A. Hollingsworth, Dominick J. Dimaio, Jean L. Grem, Surinder K. Batra, Moorthy P. Ponnusamy Jan 2026

Distinct Glycosyltransferase Expression Governs Organ-Specific Survival In Pancreatic Cancer Metastasis, Venkatesh Varadharaj, Frank Leon, Nivedeta Krishna Kumar, Palanisamy Nallasamy, Pratima Raut, Annant Bir Kaur, Kirtana Arikath, Wyatt Petersen, Sanchita Rauth, Neelanjana Gayen, Zahraa Wajih Alsafwani, Poompozhil Mathivanan, Saravanakumar Marimuthu, Kavita Mallya, Madhu Bommideni, Jesse L. Cox, G. Talmon, Paul M. Grandgenett, Michael A. Hollingsworth, Dominick J. Dimaio, Jean L. Grem, Surinder K. Batra, Moorthy P. Ponnusamy

Journal Articles: Biochemistry & Molecular Biology

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal cancers, with over 83% of patients presenting metastases to vital organs such as the liver, lungs, and peritoneum. Although glycosylation has been established as a critical factor in PDAC development, little is known about the molecular underpinnings of organ-specific metastasis. In this study, we investigated the role of glycosyltransferases (GTs) in mediating PDAC metastatic organotropism. Through an unbiased transcriptomic screen, we identified distinct GT expression patterns in liver- and lung-tropic PDAC cells. Notably, GCNT3 and B3GNT3 were selectively upregulated in liver and lung-tropic cells, respectively. These mutually exclusive expression patterns were …


From Screens To Stress: Public Health Implications Of Cancer Worry In A Digitally Connected World, Shreya Mathur, Ethan Burns, Michael Pokojovy, Tzu-Liang Bill Tseng, Sunil Mathur Jan 2026

From Screens To Stress: Public Health Implications Of Cancer Worry In A Digitally Connected World, Shreya Mathur, Ethan Burns, Michael Pokojovy, Tzu-Liang Bill Tseng, Sunil Mathur

Mathematics & Statistics Faculty Publications

Aims:

This study examines how digital information environments, genetic testing experiences, health behaviors, and psychological distress influence cancer-related worry among adults in the United States. It further considers the public health implications of elevated or reduced cancer worry for prevention and risk communication.

Methods:

Data were drawn from a nationally representative survey of 6,252 U.S. adults. Measures included reliance on social media for health decision-making, smoking status, history of genetic testing, and psychological distress. Multivariable analyses assessed associations between these factors and levels of cancer worry.

Results/Findings:

Reliance on social media for health decisions was associated with greater cancer worry, …


Dupilumab In Chronic Rhinosinusitis Without Nasal Polyps: Randomized Phase 2 Trial (Orion), Stella E. Lee, Anju T. Peters, Philippe Gevaert, Joseph K. Han, Claus Bachert, Francisco Moreira Da Silva, Andrés Rosenblüt, Chih-Chi Hu, Jennifer Maloney, Paolo Caferra, Adrianna Michalak, Andrew P. Fontenot, Lacey B. Robinson, Neelam A. Phadke Jan 2026

Dupilumab In Chronic Rhinosinusitis Without Nasal Polyps: Randomized Phase 2 Trial (Orion), Stella E. Lee, Anju T. Peters, Philippe Gevaert, Joseph K. Han, Claus Bachert, Francisco Moreira Da Silva, Andrés Rosenblüt, Chih-Chi Hu, Jennifer Maloney, Paolo Caferra, Adrianna Michalak, Andrew P. Fontenot, Lacey B. Robinson, Neelam A. Phadke

Department of Otolaryngology (ENT) Faculty Publications

BACKGROUND: Chronic rhinosinusitis (CRS) is often driven by type 2 inflammation and is characterized by nasal obstruction/ discharge, facial pain/pressure, and/or reduced smell, either with or without nasal polyps (CRSwNP or CRSsNP).

OBJECTIVE: To test whether dupilumab improves radiographic features in CRSsNP. Methods: ORION (NCT04678856), a phase 2, randomized, multicenter, double blind, placebo-controlled study, assessed dupilumab efficacy and safety in adults with uncontrolled CRSsNP. Patients were randomized 1:1 to dupilumab or placebo for 24 to 52 weeks. Endpoints included changes from baseline at week 24 in Lund–Mackay computed tomography (LMK-CT) score (dupilumab only [primary] and vs placebo [secondary]), sinus Total …