Medical Sciences Commons^™

Using Randomization To Compare Ai And Expert-Generated Formative Assessment Questions In Medical Education, Akshat Kumar, Katie Stinson, Litao Wang, Elizabeth Nugent, Yongsu Lee, Mark Hormann, Latanya Jones Love, Toufeeq Ahmed Syed

Faculty, Staff and Student Publications

Background: AI-generated content is being used across the education spectrum and is beneficial for creating complex multiple-choice questions, such as those used in medical education. However, evaluating AI-generated content is challenging, and existing testing and evaluation methods are falling short. This study uses randomization to compare medical students' performance on and subjective evaluation of AI versus expert-generated questions. We hypothesized that there would be no difference in student performance or subjective evaluation of AI vs expert-generated questions.

Methods: We designed a single-center, randomized study where medical student participants received either one AI- or expert-generated question per day over four weeks. …

Limosilactobacillus Reuteri Promotes Melatonin Release From Human Intestinal Organoids Via 5′Ectonucleotidase Activity, Micah D Forshee, Erika J Nachman, Esha R Shenoy, Heather A Danhof, Ludwig Ermann Lundberg, Stefan Roos, Robert A Britton

Faculty, Staff and Students Publications

Strains of Limosilactobacillus reuteri have been used to prevent or treat various conditions; however, the mechanisms by which they exert beneficial effects are not completely understood. Infant colic is one example in which L. reuteri DSM 17938 reduces clinical symptoms. While the etiology of colic is unknown, abnormal melatonin levels in infants have been suggested as a possible contributor. L. reuteri DSM 17938 has been shown to produce adenosine from AMP via production of the extracellular enzyme 5′ectonucleotidase (5′NT). Adenosine is a potent signaling molecule that impacts several important aspects of host physiology, including the release of melatonin from the …

Steroid Receptor Coactivator 3-Deficient Regulatory T Cells Eradicate Multiple Solid Tumors In Syngeneic Mouse Models, Nuri Sung, Eunsu Kim, Yosef Gilad, Yuri Park, Adam M Dean, Yan Xia, Jianming Xu, Clifford C Dacso, David M Lonard, Sang Jun Han

Faculty, Staff and Students Publications

Steroid receptor coactivator 3 (SRC-3) is highly expressed in regulatory T cells (Tregs) and is important for their immunosuppressive activity. Recently, we demonstrated that disrupting SRC-3 expression in Tregs eliminates triple-negative breast cancer (TNBC) and prostate cancer in syngeneic animal models by generating an anti-tumor immune microenvironment without inducing immune-related adverse events (irAEs). Further analysis of these mice revealed that SRC-3 knockout (KO) Tregs infiltrated breast tumors and facilitated the infiltration of CD8

When Probiotics Guidelines Differ: A Practical Guide For Clinicians And Researchers, Geoffrey A Preidis, Hania Szajewska, Marla Cunningham, Howard Bauchner, Daniel J Merenstein

Faculty, Staff and Students Publications

Many professional organizations publish clinical practice guidelines for the use of probiotics in gastrointestinal disorders. Generally, no two guidelines align perfectly, and some differ markedly. These discrepancies occur because clinical practice guidelines are not purely mechanical outputs of data synthesis. They are shaped by structured interpretation, value judgments, and predefined thresholds for uncertainty. These elements become particularly visible when effect sizes are small, heterogeneity is high, and outcomes vary in clinical relevance-as is the case with probiotic research. This article examines why discordance among probiotic guidelines is predictable and provides practical guidance for clinicians who must decide among conflicting recommendations …

Is Your Cyst Really A Ganglion Cyst? A Case Report Of Angioleiomyoma Mimicking A Plantar Fascia Cystic Lesion, Christopher Anjorin Ms Dpmc, Joseph Bender Dpm

School of Podiatric Medicine - Student Research

Ganglion cysts are among the most common benign soft tissue masses encountered in podiatric clinical practice, and their diagnosis is often presumed based on location, clinical observation, and transillumination. However, this case highlights a diagnostic idiosyncrasy: a lesion clinically presumed to be a ganglion cyst within the plantar fascia was ultimately identified as an angioleiomyoma following surgical excision and histopathological evaluation. This finding underscores the importance of maintaining a broad differential diagnosis when assessing cystic lesions, particularly those that transilluminate, as benign vascular tumors may closely mimic more common entities in both clinical presentation and imaging. More importantly, what if …

Ambulatory Blood Pressure Variability In Prediction Of Target Organ Injury: The Ship Ahoy Study, Coral D Hanevold, Jang Dong Seo, Stephen R Daniels, Bonita E Falkner, Michael A Ferguson, Joseph T Flynn, Julie R Ingelfinger, Philip R Khoury, Marc B Lande, Kevin E Meyers, Mark Mitsnefes, Joshua Samuels, Elaine M Urbina

Faculty, Staff and Student Publications

Background: Ambulatory hypertension is associated with elevated left ventricular mass index (LVMI), cardiac dysfunction, and increased arterial stiffness in adolescents. Whether the addition of measures of BP variability improves the prediction of subclinical cardiovascular target organ damage (TOD) over mean BP measures is not known.

Methods: We assessed clinic and ambulatory BP (ABP), anthropometrics, and TOD in 397 adolescents. ABP means standard deviation (SD), BP, and heart rate (HR) dipping were calculated; coefficients of variability (CV) were calculated (SD/mean) to assess ABP variabilities. Measures of TOD included LVMI, left ventricular hypertrophy (LVH), LV systolic shortening, LV diastolic function (e'/a'), and …

A Genomic Approach For Accurate Identification Of Closely Related Species With Next-Generation Sequencing Samples, Nour Al Dain Marzouka, Amira Al-Aamri, Fatima Alshamsi, Mariam Khalili, Sarah El Hajj Chehadeh, Meera S. Mohamed, Yassir Mohammed Eltahir, Rafeek Koliyan, Mohamed Moustafa Abdelhalim, Assem Attia, Mira Mousa, Guan Tay, Habiba Alsafar

Research outputs 2022 to 2026

Accurate species identification from Whole Genome Sequencing (WGS) data remains challenging, particularly for closely related species such as sheep (Ovis aries) and goats (Capra hircus). Through analysis of mapping quality metrics and Kraken2 taxonomic classification of 40 WGS sheep and goat samples, we demonstrate that conventional approaches yield ambiguous results, with overlapping alignment rates and inconclusive taxonomic assignments. We present a robust comparative genomic approach that uses species-specific genomic regions to distinguish these species in WGS samples. We define species-specific regions as those exhibiting distinctive coverage patterns: average coverage when samples are aligned to their matching reference genome but absent/low …

The Relationship Between Dietary Sodium Intake And Cognitive Function: A Narrative Review, Samantha L. Gardener, M. Fu, L. Morini, T. Schwartzkopff, G. Savage, R. N. Martins, S. R. Rainey-Smith

Research outputs 2022 to 2026

Purpose of Review: This narrative review provides discussion on current evidence regarding the relationship between sodium intake and cognitive function in animal and human studies, as well as potential mechanisms underlying this relationship. Recent Findings: Recent evidence suggests high sodium intake is associated with development of cognitive impairment and neural dysfunction. Additionally, studies have proposed that high sodium intake is associated with increased aggregation of Aβ-amyloid and that hypertension (for which high sodium intake is a risk factor) modulates the relationship between Aβ-amyloid and development of cognitive impairment and Alzheimer’s disease. However, while animal studies demonstrate a consistent relationship between …

Genetic Drivers Of Progression In Alzheimer’S Disease Are Distinct From Disease Risk, Celeste E. Cohen, Shane Fernandez, Umran Yaman, Ahmad R. Ehyaei, Eleftheria Kodosaki, Aydan Askarova, Tenielle Porter, Eleanor O’Brien, Paul Maruff, Alexi Nott, John A. Hardy, Simon M. Laws, Dervis A. Salih, Maryam Shoai

Research outputs 2022 to 2026

Background: Recent trials in Alzheimer’s disease (AD) demonstrate encouraging outcomes. These trials target risk mechanisms identified through genetic analysis whilst directly aiming to reduce progression rates. Evidence from other neurodegenerative diseases suggests the genetics of progression is distinct from risk of disease. To expand these initial successes and improve clinical outcomes further we need to understand genetics of progression of disease. These can be deduced through rigorous analysis of meticulously phenotyped longitudinal cohorts. In this study we first looked at known genetic drivers of risk, namely polygenic risk scores for AD and APOE‑ε4, to assess their role in progression. This …

Mtorc2-Nav1.2 Signaling Drives Early Hyperexcitability In Alzheimer’S Disease Mouse Model, Nolan M Dvorak, Jeffrey L Noebels

Faculty, Staff and Students Publications

Hyperexcitability is a biomarker of early-stage Alzheimer’s Disease (AD) and hastens cognitive decline later in its course. Mechanistic target of rapamycin (mTOR) signaling contributes to the slope of this trajectory, as evidenced by early increased brain expression and the rescue of hyperexcitability by genetic deletion of mTOR complex 2 (mTORC2); however, a molecular mechanism directly linking mTOR signaling to membrane hyperexcitability in early-stage AD remains elusive. Here, we show that hyperactive mTOR signaling stimulates the voltage-gated Na+ channel 1.2 (Nav1.2), a previously identified downstream phosphorylation target of mTORC2 and a key regulator of membrane electrogenesis. Augmented Nav1.2 channel function induced …

In-Hospital Mortality Patterns And Readmissions In Patients With Chronic Obstructive Pulmonary Disease: An Analysis Of The Role Of Pulmonary Hypertension, Saad Afzal Khan, Trishna Parikh, Adishwar Rao, Akriti Agrawal, Aarohi Parikh, Farah Kazzaz, Sarah Shin, Harry Karmouty-Quintana, Maulin Patel, Kha Dinh, Bela Patel, Bindu Akkanti

Faculty, Staff and Student Publications

Chronic obstructive pulmonary disease (COPD) may be complicated by pulmonary hypertension (PH). We aimed to understand the impact of PH on in-hospital mortality and quantify the 30-day readmission rate among patients with COPD. For this cross-sectional study, we used the Nationwide Readmissions Database from 2017-2020 to identify adults ≥18 years with COPD. Patients were stratified according to PH diagnosis. Baseline characteristics between groups were compared using the Pearson chi-square test and two-sample t-test. Predictors of in-hospital mortality were determined using multivariate logistic regression analysis adjusted for demographics and confounders. The 30-day readmission rate and prevalence of PH subgroups by baseline …

Discriminative Performance Of Externally Validated Dementia Risk Prediction Models: A Systematic Review And Meta-Analysis, Blossom C.M. Stephan, Jacob Brain, Kaarin J. Anstey, Tanya Buchanan, Claire V. Burley, Elissa Burton, Jennifer Dunne, Linda Errington, Matthew Gorringe, Zhongyang Guan, Bronwyn Myers, Serena Sabatini, Marc Sim, William Stephan, Eugene Yee Hing Tang, Narelle Warren, Mario Siervo

Research outputs 2022 to 2026

Background: Data on the external validation of current dementia risk prediction models has not yet been systematically synthesised. This systematic review and meta-analysis collated results from three previous reviews to evaluate the predictive discriminative performance of dementia risk models when validated in population-based settings. Methods: Embase (via Ovid), Medline (via Ovid), Scopus, and Web of Science were searched from inception to June 2022 with an updated search conducted up to November 2024. Included studies (1) had a population-based cohort design; (2) assessed incident late-life (i.e. ≥ 60 years) dementia; and (3) reported predictive performance of at least one dementia risk …

Corrigendum To “Characterizing The Metabolites Of The Tyrosine-Kinase Inhibitor Pexidartinib In Mouse Feces, Urine, Plasma, And Liver” [J. Pharm. Biomed. Anal. 265 (2025) 117034], Xuan Qin, Si Chen, John M Hakenjos, Jian Wang, Lei Guo, Ashish Dogra, Zhaoyong Hu, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

No abstract provided.

Dean's Report- Fall 2026, Marina K. Holz

GSBMS Dean’s Report

No abstract provided.

Adjunctive Embolization Of Target Vessel Dissections To Improve Suitability For Fenestrated-Branched Endovascular Aortic Repair, Zemia C Ferreira, Hannah V Oden-Brunson, Ying Huang, Steven Maximus, Naveed Saqib, Erin Greenleaf, Thanila A Macedo, Gustavo S Oderich

Faculty, Staff and Students Publications

Suitability of renal-mesenteric target arteries is an essential criterion for fenestrated-branched endovascular aortic repair (FB-EVAR). We describe a staged adjunctive technique of target vessel false lumen (FL) embolization to improve suitability for FB-EVAR in patients with chronic postdissection thoracoabdominal aortic aneurysms (PD-TAAA) and dissection extension into the superior mesenteric artery (SMA). Three patients with SMA dissection and ectasia (diameter > 12-14 mm) underwent staged FL embolization with pre-emptive stent placement to optimize SMA incorporation. Using bilateral transfemoral access with intravascular ultrasound guidance, the proximal SMA true lumen was stented with an 8 L × 39 mm VBX balloon-expandable stent graft (W. …

Newborn Screening Reduces Survival Disparities In Scid After Stem Cell Transplant: A Pidtc Report, Lena E Winestone, Brent R Logan, Xuerong Liu, Olatundun Williams, Elizabeth A Dunn, Monica S Thakar, Sharon A Kidd, Talal Mousallem, Morna J Dorsey, Richard J O'Reilly, Neena Kapoor, Lisa Forbes Satter, Malika Kapadia, Soma C Jyonouchi, Sharat Chandra, Christen L Ebens, Deepakbabu Chellapandian, Sonali Chaudhury, Karin Chen, Blachy J Dávila Saldaña, Ahmad Rayes, Troy C Quigg, Shanmuganathan Chandrakasan, Jeffrey J Bednarski, Kenneth B Desantes, Pierre Teira, Alfred P Gillio, Hesham Eissa, Alan P Knutsen, Victor M Aquino, Evan B Shereck, Theodore B Moore, Emi H Caywood, Mark T Vander Lugt, Jacob Rozmus, Larisa Broglie, Lolie C Yu, Ami J Shah, Avni Y Joshi, Rebecca H Buckley, Jasmeen Dara, Joseph H Oved, Hisham Abdel Azim, Caridad A Martinez, Susan Prockop, Kathleen E Sullivan, Jack J Bleesing, Michael D Keller, Lisa M Madden, Suhag Parikh, Shalini Shenoy, Christine M Seroogy, Tamar Rubin, Jennifer Licata, Jeffrey R Andolina, Donald B Kohn, Lauri Burroughs, Jennifer W Leiding, Rebecca A Marsh, Luigi D Notarangelo, Sung-Yun Pai, Troy R Torgerson, Michael A Pulsipher, Jennifer Heimall, Geoffrey D E Cuvelier, Linda M Griffith, Jennifer M Puck, Christopher C Dvorak, Morton J Cowan, Elie Haddad

Faculty, Staff and Students Publications

Black race and Hispanic ethnicity are associated with higher mortality in severe combined immunodeficiency (SCID) following hematopoietic cell transplantation (HCT), though mechanisms remain unclear. We evaluated 796 children with SCID who received nonsibling HCT between 1982 and 2020 using data from the Primary Immune Deficiency Treatment Consortium. Overall survival for Black (aHR 2.47, 95%CI 1.64, 3.71) and Asian/Pacific Islander patients (aHR 1.82, 95%CI 1.00, 3.30) was significantly lower compared with non-Hispanic White patients, while Hispanic patients had lower event-free survival (aHR 1.83, 95%CI 1.27, 2.63) compared with non-Hispanic White patients. Even after adjusting for age and infection, Black patients with …

Neurochemical Impact Of Psychostimulants: Longitudinal Mri Analysis Of Brain Iron Content In Children With Adhd, Hugo A.E. Morandini, Sjoerd B. Vos, Paola Chivers, Tim J. Silk, Pradeep Rao

Research outputs 2022 to 2026

Background: Attention Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in school-aged children and has been associated with impaired brain iron homeostasis. Evidence has shown that psychostimulant treatment may affect brain iron content in children with ADHD, however, longitudinal evidence remains limited. The present longitudinal study investigated the effect of psychostimulant treatment duration and age at treatment onset on brain iron content in children with ADHD. Methods: Neuroimaging and phenotypical data were collected from the publicly available Oregon ADHD-1000 dataset. After screening, data from 29 psychostimulant-medicated children with ADHD and 38 neurotypical children were included. Individual General Estimating Equation (GEE) …

Mir-27a Expression During Inflammatory Organ Injury Associated With Ards And A Novel Tissue-Specific Knockout Model, Jieun Kim, Synthea Horton, Oleg D Makarevich, Yan Levitsky, Thu Thien Tran, In Hyuk Bang, Xiangsheng Huang, Xuebo Chen, Katherine Figarella, Xiaoyi Yuan

Faculty, Staff and Student Publications

No abstract provided.

Cerebellar Atrophy In Pediatric-Onset Opsoclonus-Myoclonus-Ataxia Syndrome: A Large International Cohort Study, Rebecca Macrae, Kierstin Hederstedt, Christopher Cortina, Kumaran Deiva, Andrea Klein, Ming Lim, Thomas Rossor, Elizabeth A Sokol, Yasmin Khakoo, Nikita Malani Shukla, Timothy E Lotze, Wendy G Mitchell, Sarah Hopkins, Bo Zhang, Mark P Gorman

Faculty, Staff and Students Publications

Background and objectives: Pediatric-onset opsoclonus-myoclonus-ataxia syndrome (POOMAS) is a rare, neuroinflammatory syndrome that targets the cerebellum and can cause irreversible cerebellar structural changes, namely cerebellar atrophy. We investigated the frequency of cerebellar atrophy, as well as associated risk factors and functional outcome measures, using the largest active POOMAS registry.

Methods: This was a retrospective observational study of participants with POOMAS with disease onset from 1995 to 2025 using data from the multinational, multicenter POOMAS registry. Variables were compared between the cerebellar atrophy subgroups using the Fisher exact test or Wilcoxon rank-sum test.

Results: Of participants with follow-up imaging, cerebellar atrophy …

Bivip: A Competitive Neural Network For Bilateral Visuo-Haptic Processing, Eleonore Federica Di Rosa, Aaisha Sheth, Jeffrey Min-In Yau, Laura Astolfi, Cristiano Cuppini

Faculty, Staff and Students Publications

Visuo-haptic interactions are gaining interest in perception research because of their relevance to robotics and rehabilitation. While the benefits of integrating concurrent visuo-tactile cues are well-documented, the temporal dynamics of competitive interactions between vision and touch remain less understood. Building on extant empirical evidence of unilateral intersensory switching, we ask whether bilateral detection of visual and tactile stimuli can be explained by cross-sensory competition and explore the underlying sensorineural dynamics via a multi-level neural network model. Tested against results from a speeded reaction time task to unilateral and bilateral visual, tactile, and visuo-tactile targets, the network successfully predicts higher switch …

Translational Initiative To Minimize Childhood Hemiparesis After Asymmetrical Perinatal Brain Injury, Susan V. Duff, Emily Garavatti, Terrie Inder

Physical Therapy Faculty Articles and Research

The purpose of this perspective paper is to present a translational approach aimed at identifying the critical periods in brain development during which to provide neuroprotective and neurorestorative strategies, followed by prehensile training, to minimize hemiparesis and foster skill acquisition after asymmetrical perinatal brain injury (APBI). We contend that hemiparesis could be minimized after APBI through a multimodal sequential approach based on timely implementation of evidence-based intervention strategies. If APBI is identified early, neuroprotective techniques can be used in the first 10 days of life to minimize cell death. This can be followed in the next 3 months by the …

Cells And Networks In Flux: Rethinking Ontogenesis And Pathogenesis, Mark L. Tykocinski

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Organ and tissue functions emerge from the coordinated activity of cell networks. Therapeutics that act on pathogenic cell networks, modulating their cellular interplay, follow naturally. Over several decades, our laboratory has developed a series of approaches for rewiring cell networks, culminating in a class of cell surface-directed signal converter proteins (SCPs) that do so by modulating juxtacrine and autocrine signaling in and among their nodal cells. A first such SCP has now produced encouraging clinical data for cancer immunotherapy. Yet, these early network-directed fusion proteins rest on a deliberately simplified picture: discrete end-cell types plugged into graphically tractable networks. That …

Amyloid-Related Imaging Abnormalities Summit Special Proceedings: Cardiovascular And Stroke Considerations For Β-Amyloid Immunotherapy In Alzheimer Disease., Steven M Greenberg, Costantino Iadecola, Sherry H-Y Chou, Petrice M Cogswell, Mitchell S V Elkind, William J Hicks, Caitlin Le, Deborah A Levine, Richard Lipton, Lauren Massimo, Stephanie M Mohl, Sudha Seshadri, Heather M Snyder, Kristine Yaffe, Kori S Zachrison, Aria Summit Working Group

Neuroscience Articles

BACKGROUND: New antiamyloid therapies (AAT) for treating patients with early Alzheimer disease (AD) have become available in the past 3 years. Although AAT can be beneficial in slowing progression of AD, they also come with potentially serious side effects, particularly for patients requiring anticoagulation or thrombolysis for cardiovascular conditions. Given that most patients with AD are older and likely to have cardiovascular risk factors, there is urgent need for additional guidance for clinicians about potential risks and benefits associated with AAT for patients with cardiovascular comorbidities, best practices for management of these patients, and special considerations with respect to emergency …

Selective Loss Of Primary Cilia And Neurotrophic Signaling In G51d Α-Synuclein Mice Highlights A Common Pathway To Parkinson’S Disease, Yu-En Lin, Ebsy Jaimon, Youngdoo Kim, Annabeth Loftman, Aaran Vijayakumaran, Benjamin D W Belfort, Claire Y Chiang, Benjamin R Arenkiel, Huda Y Zoghbi, Suzanne R Pfeffer

Duncan NRI Faculty and Staff Publications

Parkinson's disease is characterized by dopaminergic neuron loss and accumulation of α-synuclein aggregates in the brain. G51D α-synuclein knock-in mice provide a genetically and clinically relevant model of disease, exhibiting early olfactory deficits, age-dependent motor impairment, and progressive phospho-α-synuclein accumulation. In multiple Parkinson's disease models, striatal cholinergic and parvalbumin interneurons, as well as astrocytes, lose primary cilia and the neurotrophic signaling needed to sustain dopaminergic neurons. We show here that G51D α-synuclein mice share these phenotypes. Phospho-Ser129 α-synuclein accumulation correlates with cilia loss in cholinergic interneurons but not in spiny projection neurons that accumulate higher phospho-α-synuclein levels. In the piriform …

Brain Perivascular Macrophages Regulate Endothelial Cell Function Via A Cmaf-Dependent Transcriptional Program In Mouse And Human, Simone Brioschi, Julia A Belk, Steffen E Storck, Yue Wu, Zhuoying Wang, Ziang Feng, Lynn Van Olst, Josie L Emery, Raki Sudan, Junjie Wu, Siling Du, Marco Genua, Federica La Terza, Alex J Edwards, Khai M Nguyen, Jessie Sanford, Daniel D Lee, Mattia Bugatti, Arnold J Federico, Yun Chen, Zuoxu Wang, Silvia Penati, Patrick Fernandes Rodrigues, Alina Ulezko Antonova, Hui Qi Loo, Igor Smirnov, Susan Gilfillan, Carmen M Halabi, Jennifer Ponce, Jun Yan, Howard Y Chang, Gwendalyn J Randolph, William Vermi, Marina Cella, Michael Meers, Renato Ostuni, David Gate, Aivi T Nguyen, Carlos Cruchaga, Song Hu, Jonathan Kipnis, Marco Colonna

The Brown Foundation: Institute of Molecular Medicine

Brain perivascular macrophages maintain brain physiology, yet their transcriptional regulators and functions in health and disease remain unclear. Using single-cell multi-omics and functional experiments, we identify cellular musculoaponeurotic fibrosarcoma oncogene (cMAF) as a key transcription factor for brain perivascular macrophages, and conditional deletion of cMAF disrupts their phenotype in vivo. Functionally, cMAF drives insulin-like growth factor-1 (IGF1) expression in perivascular macrophages, enabling communication with endothelial cells. Consistently, cMAF deletion in perivascular macrophages causes transcriptional alterations in cerebral arteries, affecting vascular functions. Notably, cMAF emerges as the main transcription factor for human perivascular macrophages, suggesting conservation of this transcriptional module. During …

Telomere-To-Telomere Genome Assembly And A Pangenome For The Rat, Kai Li, Julia L Ciosek, Sergey Koren, Adam M Phillippy, Yaming Zhu, William A Lauer, Shelise Y Brooks, Gerard G Bouffard, Brandon D Pickett, Beth L Dumont, Melissa L Smith, Theodore S Kalbfleisch, Peter A Doris

The Brown Foundation: Institute of Molecular Medicine

We report a complete rodent telomere-to-telomere genome assembly from the brown rat, Rattus norvegicus. Annotation was enriched with multi-tissue long-read RNA sequencing and uncovered numerous novel genes. Assembly of both sex chromosomes reveals the absence of gene coding in the presumed pseudo-autosomal regions and the presence of centromeric satellite repeats on distal chromosome Y (chrY). We provide evidence of meiotic conjunction between Xp and Yq. The genome assembly reveals several expanded autosomal regions enriched for testis-expressed genes. Finally, we have generated a pangenome from recent high-quality assemblies of 8 distinct inbred rat strain genomes. This allows the strain-specific distribution of …

Bcg Overexpressing Ag85b Reprograms Host Immune Response Through Coordinated Transcriptional Networks, Vivek Chauhan, Rakesh Kumar, Raja Veerapandian, Enrique I. Ramos, Chinnaswamy Jagannath, Shrikanth Gadad, Subramanian Dhandayuthapani

School of Medicine Publications

Antigen 85B (Ag85B), an immunodominant protein secreted by Mycobacterium tuberculosis (Mtb), induces robust T-cell-mediated immunity in host cells. Previous studies have demonstrated that recombinant BCG strains overexpressing Ag85B (BCG85B) confer significant protection against tuberculosis in mouse models. This study hypothesized that enhanced protection by recombinant BCG85B results from modulation of host immune gene expression by the Ag85B antigen. To test this, RNA-seq analysis was performed on splenocytes from mice immunized with the wild-type BCG (BCG-WT) and BCG85B strains. Differentially expressed genes (DEGs) in the splenocytes of BCG85B-immunized mice indicated upregulation of immune-related KEGG pathways, including Th1/Th2 and Th17 differentiation, NF-kappa …

Runx1+23 Enhancer Marks Erythro-Megakaryocyte Lineages In Early Waves Of Hematopoiesis In Human Esc Differentiation, Chika Nishida, Michihiro Kobayashi, Alina Syed, Philipp Kramer, Haizi Cheng, Pamela L Wenzel, Motomi Osato, Jason David Chobirko, Andrew Grimson, Igor I Slukvin, Brian R Davis, Momoko Yoshimoto

The Brown Foundation: Institute of Molecular Medicine

No abstract provided.

Cigarette Smoke Induces Fasn-Dependent Fatty Acid Metabolic Rewiring To Drive Bladder Cancer Progression, Chandra Sekhar Amara, Danthasinghe Waduge Badrajee Piyarathna, Abu Hena Mostafa Kamal, Yuen San Chan, Karthik Reddy Kami Reddy, Chandra Shekar R Ambati, Mohammed Khurshidul Hassan, Pratik Shriwas, Tanmay Gandhi, Antrix Jain, Tanja Gangnus, Pooja Popli, Roshan Borkar, Sung Wook Kang, Silvia L Summers, Vasanta Putluri, Sandra L Grimm, Sharan Venkatesh, Ningxin Song, Erin H Seeley, Jenna Hedlich-Dwyer, Shu-Hsia Chen, Nupam P Mahajan, Abhinav K Jain, Lacey Elizabeth Dobrolecki, Gabrielle A Wells, Hugo Villanueva, Jenny Li, Xuefeng Liu, Roni J Bollag, Anna Malovannaya, Sung Yun Jung, Hyun-Sung Lee, Irfan A Asangani, Martha K Terris, Chad J Creighton, Leomar Y Ballester, Balasubramanyam Karanam, Suyu Liu, Minjae Lee, Rajeeva R Raju, M Minhaj Siddiqui, Livia S Eberlin, Ramakrishna Kommagani, Arun Sreekumar, Jianjun Gao, Nicolas L Young, H Courtney Hodges, Cristian Coarfa, Natalie R Gassman, Seth P Lerner, Yair Lotan, Nagireddy Putluri

Faculty, Staff and Students Publications

Cigarette smoke promotes bladder tumor growth by enhancing cancer cell survival and proliferation through smoke mediated carcinogens. FASN, a key enzyme in fatty acid synthesis, is dysregulated in many cancers and correlates with aggressive phenotypes. In this study, we demonstrate elevated fatty acid levels and FASN specifically in smokers with bladder cancer. Elevated FASN under smoke exposure imparted epigenetic alterations, particularly histone acetylation, impacts DNA repair and DNA-binding transcription factors which regulate metabolic pathways. Under cigarette smoke, bladder cancer cells undergo a metabolic shift, utilizing glutamine as a major carbon source through reductive carboxylation to fuel fatty acid biosynthesis via …

A Distinct Form Of Fat Fibrosis Is Linked To Insulin Resistance In People With Hiv, Diana L Alba, Alaa Abdellatif, Moon Kyung Choi, Stephen M Brown Mayfield, Thuy An T Pham, David I Berrios, Antonio E Rodriguez, Marin Ewing, Tony R Figueroa, Judy Gonzalez-Vargas, Ningyan Zhang, Zhiqiang An, Dawei Bu, Steven G Deeks, Philipp E Scherer, Peter W Hunt, Suneil K Koliwad

The Brown Foundation: Institute of Molecular Medicine

BACKGROUND

Despite antiretroviral therapy (ART), people with HIV (PWH) are at heightened risk for insulin resistance (IR) and type 2 diabetes (T2D). Subcutaneous adipose tissue (SAT) fibrosis contributes to metabolic disease, but its role in IR among PWH is unknown. We investigated the relationship between SAT fibrosis and IR in PWH, along with transcriptional signatures to distinguish it from SAT fibrosis due to obesity.

METHODS

We analyzed body composition and SAT fibrosis (hydroxyproline) in 46 PWH and 74 people without HIV (PWoH), excluding individuals with T2D. We examined fibrosis-related gene transcription in the SAT using a targeted panel and measured …