Medical Specialties Commons^™

Limosilactobacillus Reuteri Promotes Melatonin Release From Human Intestinal Organoids Via 5′Ectonucleotidase Activity, 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 …

Mucin-Derived Sugars Act As Metabolic Brakes Controlling Growth Initiation In Akkermansia Muciniphila, Bryan D Lakey, Katherine J Wozniak, Robert A Britton, Jeffrey J Tabor

Faculty, Staff and Students Publications

Akkermansia muciniphila is a key member of the gut microbiota and plays important roles in host metabolism and health. In the colon, A. muciniphila extracts nutrients from oligosaccharide-rich mucin glycans that comprise the mucosa. However, this environment is complex and shaped by dietary inputs, microbiome metabolism, and mucin glycan composition varying across hosts, gastrointestinal regions, and physiological states. How strains of A. muciniphila integrate these nutrient signals into growth initiation and niche colonization remains unclear. Here, we compare physiological responses of a human- and mouse-derived strain of A. muciniphila, finding that dietary sugars differentially affect these isolates, suggesting host-associated …

Gut-Derived Bacterial Extracellular Vesicles: The Microbial Dark Matter Contributing To Host Inflammation And Cardiometabolic Disease, Blayne Oliver, Michael Sun, Young Seo Lee, Ssanggoo Cho, Tianyi Zhu, David Durgan, Gary Sweeney

Faculty, Staff and Students Publications

Cardiometabolic diseases (CMDs) represent a growing global health burden, with chronic inflammation and gut microbiota dysbiosis emerging as central contributors to their pathogenesis. Among the diverse microbial products influencing host physiology, bacterial extracellular vesicles (BEVs) have gained attention as potent mediators of interkingdom communication. These nanoscale vesicles, secreted by both gram-positive and gram-negative bacteria, carry a complex cargo of proteins, lipids, nucleic acids, and pathogen-associated molecular patterns (PAMPs) that interact with host pattern recognition receptors (PRRs) to modulate immune and metabolic responses. BEVs can traverse intestinal barriers, disseminate systemically, and accumulate in cardiometabolic tissues, where they influence inflammation, insulin sensitivity, …

When Probiotics Guidelines Differ: A Practical Guide For Clinicians And Researchers, 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 …

Steroid Receptor Coactivator 3-Deficient Regulatory T Cells Eradicate Multiple Solid Tumors In Syngeneic Mouse Models, 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

Mtorc2-Nav1.2 Signaling Drives Early Hyperexcitability In Alzheimer’S Disease Mouse Model

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 …

A Massively Parallel Reporter Assay Of Mecp2 Cis-Regulatory Elements Reveals Genetic Candidates For Male-Biased Autism, Rebecca Meyer-Schuman, Fisher Cherry, Yang Sui, Athanasios Papastathopoulos-Katsaros, Yi Zhong, Yidan Li, Tianyun Wang, Kelsey Hennick, Druha Karunakaran, Hanna Berk-Rauch, Zhandong Liu, Aravinda Chakravarti, Tomasz Nowakowski, Evan E Eichler, Huda Zoghbi

Faculty, Staff and Students Publications

Autism affects male individuals four times more often than female individuals, yet the basis of this sex bias remains unclear. One hypothesis is that this sex bias is due to genetic variants in X chromosome genes where haploinsufficiency causes neurodevelopmental disorders (NDDs). In heterozygous XX female probands, a complete loss-of-function variant in one of these genes often causes syndromic NDD, but the same variant is too deleterious for survival in hemizygous XY males. A mild hypomorphic variant, however, may be tolerated in a female carrier but may produce milder neurological phenotypes in a male proband. We tested this by investigating …

Forniceal Deep Brain Stimulation Improves Memory In Rett Syndrome Mice By Promoting The Maturation Of Newborn Hippocampal Neurons, Qi Wang, Bin Tang, Zhenyu Wu, Huda Y Zoghbi, Jianrong Tang

Faculty, Staff and Students Publications

Deep brain stimulation (DBS) is associated with an increase in hippocampal neurogenesis and memory benefits, but the causal mechanism is unclear. Here, we use a mouse model of Rett syndrome, a severe learning disability syndrome caused by MECP2 loss of function, to find that DBS promotes the maturation and integration of newborn dentate granule cells (DGCs) into the neural circuit. Suppressing hippocampal neurogenesis prevented DBS from improving learning and memory. Newborn methyl-CpG-binding protein 2 (MeCP2)-deficient DGCs in Rett syndrome mice showed attenuated development and synaptic dysfunction, but DBS rescued DGC dendritic arborization, synaptogenesis, and long-term synaptic plasticity. DBS achieves this, …

Multiple Quality Control Checkpoints Safeguard Small Nuclear Rna Biogenesis And Prevent Assembly Of Aberrant Spliceosomes, Tiantai Ma, Claire Huntington, Zhuoyi Song, Rea M Lardelli, Eric L Van Nostrand, Jens Lykke-Andersen

Faculty, Staff and Students Publications

Defective small nuclear (sn)RNAs are produced from hundreds of human snRNA pseudogenes and mutant snRNA genes associated with human developmental disorders. Machineries that prevent defective snRNAs from disrupting pre-mRNA splicing remain poorly defined. Here, we identify multiple checkpoints in snRNA biogenesis monitored by quality control machineries that subject defective snRNAs to degradation and prevent their assembly into spliceosomes. We show that variant U1 snRNAs produced from human pseudogenes, some at rates approaching canonical snRNAs, are impaired in 3' cleavage and targeted for degradation by the NEXT-exosome while failures in subsequent protein assembly steps promote NEXT-exosome- or terminal uridylyl transferase 4/7-mediated …

Hyaluronic Acid Rectal Wall Infiltration And Reversal In Patients With Prostate Cancer Undergoing Radiation Therapy-A Case Series, Michael K Rooney, Stephen R Lee, Stephen E Mcrae, Ketan Y Shah, Mohamed E Abdelsalam, Ethan Y Lin, Comron Hassanzadeh, Seungtaek Choi, Quynh-Nhu Nguyen, Steven J Frank, Mohamed Shelan, Lauren L Mayo, Sean Mcguire, Steven Yevich, Osama Mohamad

Faculty, Staff and Students Publications

No abstract provided.

Relationship Extraction For Adverse Drug Events In Clinical Notes Using Large Language Models: A Retrospective Cross-Sectional Study, Joseph M Plasek, Yiming Li, Mary G Amato, Dinah Foer, Diane L Seger, Shayma Alzaidi, Huiyuan Zhou, Gretchen Purcell Jackson, David W Bates, Li Zhou

Faculty, Staff and Students Publications

Background: Adverse drug events (ADEs) are a critical indicator of patient safety but are often documented only in free-text clinical notes. The potential of recent advances in natural language processing (NLP), particularly generative large language models (LLMs), to identify ADEs remains understudied. This study aimed to compare the performance of multiple LLMs in identifying ADE-Drug relationships in inpatient and ambulatory clinical notes.

Methods: We used clinical notes from the 2018 National NLP Clinical Challenge (n2c2) ADE dataset (inpatient; n = 505) and from outpatient encounters (n = 2555) between October 1, 2018, and December 31, 2019, at a large academic …

Glial Dysfunction And Memory Impairments In A Model Of Pediatric Obstructive Sleep Apnea, Thea Zlatkov, Akdes Serin Harmanci, Christopher J Yates, Kenneth Nobleza, Roshan Ailani, Adam C Adler, Farrah Kheradmand, Hyun Kyoung Lee, Benjamin Deneen, Hyun-Hwan Jeong, Arvind Chandrakantan

Faculty, Staff and Students Publications

Pediatric obstructive sleep apnea (POSA) is a common childhood disease that often causes aberrant brain development and cognitive deficits. The pathophysiological underpinnings of cognitive impairments in POSA remain unclear. Here, we examined cellular and molecular aspects of pathology in a mouse model of POSA that features learning and memory deficits. We performed single-nucleus RNA-sequencing (snRNA-seq) of the hippocampus to examine gene expression changes in an unbiased and cell type-specific manner. This dataset revealed a striking perturbation of transcriptomes across all brain cell types, particularly within glia and neural stem cells. We validated reduced expression of several differentially expressed genes at …

Natural History Of Pi-Rads 3 Lesions On Serial Prostate Mpmri, Ron Marom, Yuval Rand, Meitar Atias, Sophie Barnes, Ibrahim Fahoum, Gal Keren-Paz, Mario Sofer, Ofer Yossepowitch, Snir Dekalo, Avi Beri, Roy Mano

Faculty, Staff and Students Publications

Objective: PI-RADS 3 lesions on prostate multiparametric MRI (mpMRI) are indeterminate findings with debated management. We evaluated their radiologic evolution on follow-up mpMRI and correlated imaging changes with biopsy outcomes.

Methods: We retrospectively identified 166 men with at least one PI-RADS 3 lesion on initial mpMRI and at least one follow-up mpMRI without intervening treatment. Lesions were classified at follow-up as regressed (downgraded to PI-RADS ≤ 2), stable (remained PI-RADS 3), or progressed (upgraded to PI-RADS 4-5). Lesions were stratified by zonal location. MRI-targeted biopsy results were reviewed when available (n = 64).

Results: On follow-up, 52% of lesions regressed, …

Comparative Performance Of Predictive Nomograms For Pathological Upstaging In Clinical T1 Renal Masses: An Independent External Validation, Michael Vainrib, Amos Neheman, Omri Schwarztuch Gildor

Faculty, Staff and Students Publications

Background: Preoperative identification of pathological upstaging (≥ pT3a) in clinical T1 (cT1) renal masses is critical for surgical planning. We externally validated three established predictive models, Barra, Nocera, and Mei, to assess their discrimination, calibration, and clinical utility in a contemporary cohort.

Patients and methods: We retrospectively reviewed patients undergoing surgery for cT1 renal masses at our institution. The primary endpoint was pathological upstaging to pT3a. Model performance was evaluated using the Area Under the Curve (AUC) for discrimination and the Brier Score for overall accuracy. Calibration was assessed using parametric and nonparametric Loess-smoothed curves. Clinical utility was quantified using …

Genome Sequence Of Clostridioides Difficile Prb1128, A Rt023 Strain Containing A Mobile Genetic Element Allowing For Xylitol Utilization, Katherine J Wozniak, Jeroen Corver, Ed J Kuijper, Wiep Klaas Smits, Robert A Britton

Faculty, Staff and Students Publications

Clade 3 strains of Clostridioides difficile, dominated by PCR ribotype 023 (RT023) strains, remain the least well studied in the phylogeny. We sequenced a strain of RT023 C. difficile (PRB1128) to gain molecular genetic insights and add to the limited repository of RT023 genomes in existence.

Progressive Remodeling Of Global Protein Interaction Networks In A Mouse Model Of Tauopathy, Noah Lampl, Morgan C Stephens, Zihan Wang, Joseph T Nigro, Alejandro Rondon Ortiz, Ryan Hekman, Anna Lourdes F Cruz, Rebecca Roberts, Lulu Jiang, Juan Botas, Andrew Emili, Benjamin Wolozin

Faculty, Staff and Students Publications

Neurodegenerative disease is marked not just by loss of proteins or cells, but by dynamic rewiring of macromolecular interaction networks that precede and drive pathology. Here, we present a temporally resolved, systems-scale map of multi-protein complex remodeling in a tauopathy model, integrating co-fractionation mass spectrometry, quantitative phosphoproteomics, and machine learning to decode phosphorylation-dependent shifts in protein interactomes across disease progression. This interactomic atlas serves as a resource to investigate functional assemblies, including MAPT-Dpysl2 and Cyfip1-actin, as well as ptk2b-Kars/Dars and ptk2b-Msn-Farsb-complexes, that modulate early disease phenotypes in vivo. Notably, it captures the composition, dynamics, and regulatory state of protein complexes …

Progressive Remodeling Of Global Protein Interaction Networks In A Mouse Model Of Tauopathy, Noah Lampl, Morgan C Stephens, Zihan Wang, Joseph T Nigro, Alejandro Rondon Ortiz, Ryan Hekman, Anna Lourdes F Cruz, Rebecca Roberts, Lulu Jiang, Juan Botas, Andrew Emili, Benjamin Wolozin

Faculty, Staff and Students Publications

Neurodegenerative disease is marked not just by loss of proteins or cells, but by dynamic rewiring of macromolecular interaction networks that precede and drive pathology. Here, we present a temporally resolved, systems-scale map of multi-protein complex remodeling in a tauopathy model, integrating co-fractionation mass spectrometry, quantitative phosphoproteomics, and machine learning to decode phosphorylation-dependent shifts in protein interactomes across disease progression. This interactomic atlas serves as a resource to investigate functional assemblies, including MAPT-Dpysl2 and Cyfip1-actin, as well as ptk2b-Kars/Dars and ptk2b-Msn-Farsb-complexes, that modulate early disease phenotypes in vivo. Notably, it captures the composition, dynamics, and regulatory state of protein complexes …

Fgfr1/Klb-Mfg-E8 Maintains Microvascular Integrity And Adaptive Cardiac Remodeling, Sanskruti R Gare, Nasser H Alatawi, Xinyi Chen, Jiayan Zhang, Claire Ross, Oveena Fonseka, Yihua Han, Namrita Kaur, Andrea Ruiz-Velasco, Xiangjun Zhao, Yingjuan Liu, Riham R E Abouleisa, Susanne S Hille, Tao Wang, Sabu Abraham, Bernard D Keavney, Martin K Rutter, Elizabeth J Cartwright, Gareth Howell, Tamer M A Mohamed, Oliver J Müller, Wei Liu

Faculty, Staff and Students Publications

Background: Endothelial defects in the heart are a contributor to cardiac pathological remodeling and dysfunction, which can be influenced by cardiomyocytes. Here, we explore cardioprotective crosstalk between cardiomyocytes and endothelial cells under diabetic conditions.

Methods: Type 2 diabetes was induced in male and female mice using a high-fat, high-sucrose diet in conjunction with low-dose streptozotocin. Cardiomyocyte-specific deletion of FGFR1 (fibroblast growth factor receptor 1) or KLB (beta-Klotho) was achieved by crossing floxed mice with αMHC (alpha-myosin heavy chain)-Cre transgenic mice, while the treatment potential was assessed by recombinant adeno-associated virus 9 delivery systems or administration of recombinant protein. Various in …

Frequency-Dependent Cerebellar Circuits Independently Gate Social Vocalizations And Movement, Tao Lin, Benjamin R Arenkiel, Roy V Sillitoe

Faculty, Staff and Students Publications

Communication depends on precise coordination between motor execution and cognition. Here we reveal that the cerebellum exerts real-time control over social vocalizations in adult mice. Optogenetic activation of excitatory cerebellar output in the superior cerebellar peduncle suppressed ultrasonic vocalizations with frequency-dependent potency while inducing distinct motor phenotypes. Systematic functional mapping across cerebellar regions and cell types revealed that vocal suppression can occur in the absence of overt motor impairment, suggesting selective control of vocal output beyond gross movement disruption. We identified the periaqueductal gray (PAG), a conserved midbrain vocal control center, as a key downstream mediator of this effect. Deep …

Aberrant One-Carbon Metabolism And Ancestral Genetics Underlie Edematous Severe Acute Malnutrition, Aarti Jajoo, Jared Redmond, Aparna Haldipur, Solome Zewdu, Emilyn Banfield, Shanker Swaminathan, Sharon Howell, Orgen Brown, Roa Sadat, Nancy J Hall, Kwesi Marshall, Katharina V Schulze, Thaddaeus May, Marvin E Reid, Carolyn Taylor-Bryan, Mark J Manary, Indi Trehan, Mamana Mbiyavanga, Wisdom A Akurugu, Colin A Mckenzie, Dhriti Sengupta, Elizabeth G Atkinson, Ananyo Choudhury, Neil A Hanchard

Faculty, Staff and Students Publications

Edematous severe childhood malnutrition is distinct from the non-edematous form of malnutrition and remains a major cause of under-five mortality. Its etiology remains unclear, although aberrant one-carbon metabolism has emerged as a potential contributor. Here, we assess genetic variants at loci known to influence one-carbon metabolism, and determine their association with edematous malnutrition in Jamaica and Malawi. Six loci show evidence of association, including four related to homocysteine and folate metabolism - AHCYL1, PRICKLE2, GABBR2, and PLD2, with SNPs at the latter three also having direct effects on homocysteine-related metabolites in Mendelian Randomization. Collectively, one-carbon metabolism-related variants were significantly associated …

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], Jian Wang, Lei Guo, Ashish Dogra, Zhaoyong Hu, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

No abstract provided.

Single-Nuclei Transcriptomics Reveals Cellular Senescence In Pediatric Anthracycline-Induced Cardiomyopathy, Hanna J Tadros, Yi Zhao, Lalita Wadhwa, Iki Adachi, Xiao Li, James F Martin

Faculty, Staff and Students Publications

Chemotherapy drugs that fight childhood cancer can age heart cells prematurely. We found this "cellular aging" throughout the hearts of children with treatment-related heart failure.

Transcriptomic Data And Biomedical Literature Synergize In Finding Pharmacologic Gene Regulators, Athanasios Papastathopoulos-Katsaros, Yi Zhong, Yidan Li, Tianyun Wang, Kelsey Hennick, Druha Karunakaran, Hanna Berk-Rauch, Zhandong Liu, Aravinda Chakravarti, Tomasz Nowakowski, Evan E Eichler, Huda Zoghbi

Faculty, Staff and Students Publications

Autism affects male individuals four times more often than female individuals, yet the basis of this sex bias remains unclear. One hypothesis is that this sex bias is due to genetic variants in X chromosome genes where haploinsufficiency causes neurodevelopmental disorders (NDDs). In heterozygous XX female probands, a complete loss-of-function variant in one of these genes often causes syndromic NDD, but the same variant is too deleterious for survival in hemizygous XY males. A mild hypomorphic variant, however, may be tolerated in a female carrier but may produce milder neurological phenotypes in a male proband. We tested this by investigating …

Expanding The Clinical And Molecular Spectrum Of Tubb2b Through Distinct Variants Identified Across Multiple Families, Haowei Du, Lauren E Westerfield, Chloe Munderloh, Divya Kalra, Yifan Wu, Yi Chen, Marie-Claude Gingras, Shalini N Jhangiani, Sarenur Yilmaz, Maha S Zaki, Daniel G Calame, Davut Pehlivan, Richard A Gibbs, Richard A Lewis, James R Lupski, Jennifer E Posey

Faculty, Staff and Students Publications

TUBB2B encodes a β-tubulin isotype essential for neuronal proliferation, migration, and organization during brain development. Pathogenic heterozygous variants in TUBB2B are associated with neurodevelopmental disorders including polymicrogyria and corpus callosum abnormalities. However, the phenotypic spectrum remains heterogeneous, most likely reflecting variant-specific effects on microtubule formation and stability. Homozygous TUBB2B variants are exceedingly rare, with one family reported to date. We describe five individuals in four families with rare TUBB2B variants. Four variants are described, including a previously reported de novo missense variant, c.292G>A (GenBank: NM_178012.5) (p.Gly98Arg), with potential phenotypic expansion including panhypopituitarism; a previously reported de novo missense variant, …

Expanding The Clinical And Molecular Spectrum Of Tubb2b Through Distinct Variants Identified Across Multiple Families, Haowei Du, Lauren E Westerfield, Chloe Munderloh, Divya Kalra, Yifan Wu, Yi Chen, Marie-Claude Gingras, Shalini N Jhangiani, Sarenur Yilmaz, Maha S Zaki, Daniel G Calame, Davut Pehlivan, Richard A Gibbs, Richard A Lewis, James R Lupski, Jennifer E Posey

Faculty, Staff and Students Publications

TUBB2B encodes a β-tubulin isotype essential for neuronal proliferation, migration, and organization during brain development. Pathogenic heterozygous variants in TUBB2B are associated with neurodevelopmental disorders including polymicrogyria and corpus callosum abnormalities. However, the phenotypic spectrum remains heterogeneous, most likely reflecting variant-specific effects on microtubule formation and stability. Homozygous TUBB2B variants are exceedingly rare, with one family reported to date. We describe five individuals in four families with rare TUBB2B variants. Four variants are described, including a previously reported de novo missense variant, c.292G>A (GenBank: NM_178012.5) (p.Gly98Arg), with potential phenotypic expansion including panhypopituitarism; a previously reported de novo missense variant, …

Autoimmune Cd4+T Cells Cause Meibomian Gland Dysfunction In An Adoptive Transfer Model, Kaitlin K Scholand, Paola A Guevara Montoya, Emre Aksan, Yangluowa Qu, Sean Paiboonfungfuang, Laura Schaefer, Elizaveta A Demianova, Elaine Vo, Sudhir Verma, Elle Joy J San Juan, Zhiyuan Yu, Tarsis F Gesteira, Vivien J Coulson-Thomas, Cintia S De Paiva

Faculty, Staff and Students Publications

Sjögren disease (SjD) is an autoimmune disease driven by autoimmune CD4+T cells that leads to an immune-mediated loss of lacrimal glands (LG). Meibomian glands are lipid-producing glands in the eyelids that help prevent tear evaporation. While the role of T cells in LG-mediated destruction is well established, it is unknown whether pathogenic T cells can cause MG dysfunction (MGD). Herein, we investigated whether autoimmune CD4+T cells induce MGD and characterized the pathophysiologic mechanisms using an adoptive transfer model. T cells were isolated from CD25KO (KOCD4) or wild-type (WTCD4) mice and transferred into Rag1KO mice. In comparison, KO cells were co-adoptively …

Mapping Long-Read Sequences To A Complete Reference Genome Reveals Uncaptured Variants Across The Β-Globin Cluster In Africans With Sickle Cell Disease, Pamela Lurie, Medhat Mahmoud, Aparna Haldipur, Yixing Han, Qing Li, Edmond Wonkam Tingang, Natalie Asmus, Emilyn Banfield, Nancy J Hall, Bamidele Tayo, Richard Cooper, Titilola Akingbola, George Ayodo, Stephen Obaro, Guillaume Lettre, Qing Meng, Shalini Jhangiani, R Alan Harris, Kim C Worley, Juyhun Kim, Arang Rhie, Adam M Phillippy, Fritz Sedlazeck, Ambroise Wonkam, Neil A Hanchard

Faculty, Staff and Students Publications

African genomes are marked by extensive complexity in the number and distribution of variants yet remain under-represented in genetic databases and the human reference genome. This gap in representation limits the broad application of genomic medicine. Sickle cell disease (SCD)-one of the most common monogenic diseases-has its highest prevalence in Africa, and variation in disease severity has consistently been linked to the β-globin locus, including levels of fetal hemoglobin (HbF). Modulation of HbF is central to current SCD gene therapies; however, the inherent complexity and variation at the locus in African genomes present a challenge to translating these advances to …

Diopt: The Drsc Integrative Ortholog Prediction Tool, 2026 Update, Austin Veal, Shinya Yamamoto, Stephanie E Mohr, Norbert Perrimon

Faculty, Staff and Students Publications

Mapping orthologous proteins is a critical step for cross-species literature mining, data integration, experimental design, and more, making the ability to quickly predict orthologs across species a key tool for functional genomic studies. The DRSC Integrative Ortholog Prediction Tool (DIOPT) was initially developed in 2011 to provide a centralized portal for identifying inferred orthologs among major model organisms. By integrating results from multiple ortholog prediction algorithms, DIOPT allows users to compare predictions across methods and prioritize high-confidence ortholog relationships. Over the years, we regularly updated the underlying genome annotations and refreshed predictions from each integrated algorithm. In addition, both the …

Immune Hallmarks Of Recurrent Immune Checkpoint Inhibitor-Mediated Inflammatory Arthritis, Synat Keam, Yuanteng Jeff Li, Yanshuo Chu, Jean H Tayar, Huifang Lu, Michael Wu, Sandeep K Agarwal, Nitin Jain, Pavlos Msaouel, Adi Diab, Linghua Wang, Cara Haymaker, Roza Nurieva, Sang T Kim

Faculty, Staff and Students Publications

Immune checkpoint inhibitor (ICI) therapy is often associated with immune-related adverse events including inflammatory arthritis (IA). However, the mechanisms underlying ICI-mediated IA (ICI-IA), especially its recurrence, are not well understood. In this study, we sought to elucidate mechanisms of recurrent ICI-IA by analyzing longitudinal synovial fluid (SF) samples from patients with ICI-IA. SF samples were collected from six patients with ICI-IA at the first and second occurrences of ICI-IA and analyzed with single-cell RNA sequencing (n = 3), single-cell T-cell receptor sequencing (n = 3), single-cell B-cell receptor sequencing (n = 3), and flow cytometry (n = 6). SF samples …

Mechanisms Of Cd4+T Tolerance To A Corneal Epithelial Neoantigen, Jeremias G Galletti, Kaitlin K Scholand, Jianming Shao, Eric P Fujisaki, Prashant Kumar, Elizaveta A Demianova, Elle Joy J San Juan, Laura Schaefer, Cintia S De Paiva

Faculty, Staff and Students Publications

Tissue-specific peripheral tolerance mechanisms are essential to prevent autoimmunity. The cornea is immune privileged, and anterior chamber-associated immune deviation (ACAID) governs its inner surface. However, the mechanisms governing corneal epithelial (outer surface) antigens remain unknown. Using an inducible, cornea-restricted neoantigen mouse model, we found that tolerance of corneal epithelial antigens is associated with antigen-specific regulatory T cell (Treg) induction. Although the cornea is both avascular and alymphatic, its epithelial antigens are still efficiently presented by ocular surface-derived antigen-presenting cells to T cells in draining lymph nodes under homeostatic conditions, leading to conventional antigen-specific Treg expansion without ocular pathology. This tolerance …