A5005545384- Immune Cell Function and Interaction
- Hematopoietic Stem Cell Transplantation
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- T-cell and B-cell Immunology
- Renal Transplantation Outcomes and Treatments
- interferon and immune responses
- Acute Lymphoblastic Leukemia research
- Cancer-related molecular mechanisms research
- Immunotherapy and Immune Responses
- Autophagy in Disease and Therapy
- Gut microbiota and health
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Virus-based gene therapy research
- Mesenchymal stem cell research
- Railway Engineering and Dynamics
- Viral Infections and Outbreaks Research
- Genomics and Chromatin Dynamics
- Cytomegalovirus and herpesvirus research
- Mycobacterium research and diagnosis
- MicroRNA in disease regulation
- Immune Response and Inflammation
- Immune cells in cancer
- Pancreatic function and diabetes
Indiana University Health
2023-2025
Indiana University – Purdue University Indianapolis
2023-2025
Indiana University
2025
Indiana University School of Medicine
2023-2025
University of Michigan–Ann Arbor
2007-2022
Michigan Medicine
2017-2021
Michigan Center for Translational Pathology
2021
Pediatrics and Genetics
2019
Bipar
2009-2010
University of Illinois Urbana-Champaign
2008
Abstract Microbiome-derived metabolites influence intestinal homeostasis and regulate graft-versus-host disease (GVHD), but the molecular mechanisms remain unknown. Here we show metabolite sensor G-protein-coupled receptor 43 (GPR43) is important for attenuation of gastrointestinal GVHD in multiple clinically relevant murine models. GPR43 critical protective effects short-chain fatty acids (SCFAs), butyrate propionate. Increased severity absence not due to baseline differences endogenous...
Innate immune pathways are early defense responses important for the immediate control and eventual clearance of many pathogens, where signaling is initiated via pattern recognition receptor (PRR)-mediated events that occur in a ligand- cell-type specific manner. Within CNS neurons, innate likely crucial to pathogens target these essential yet virtually irreplaceable cells. However, relatively little known about induction regulation neuronal PRR signaling. In this report, we used human cell...
DCs undergo metabolic reprogramming from a predominantly oxidative phosphorylation (OXPHOS) to glycolysis mount an immunogenic response. The mechanism underpinning the remains elusive. We demonstrate that miRNA-142 (miR-142) is pivotal for this shift in metabolism, which regulates tolerogenic and responses of DCs. In absence miR-142, fail switch OXPHOS show reduced production proinflammatory cytokines ability activate T cells vitro vivo models sepsis alloimmunity. Mechanistic studies miR-142...
Introduction: Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare subtype of cutaneous (CTCL) that when refractory or complicated by hemophagocytic syndrome (HPS) has poor prognosis. Romidepsin histone deacetylase inhibitor (HDACi), but its efficacy for SPTCL unknown. The allogeneic hematopoietic cell transplantation (allo-HCT) also unclear. Herein, we report case with HPS was successfully treated romidepsin followed consolidation allo-HCT. Case Presentation: A 26-year-old...
Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT) that caused by donor immune cells attacking and damaging host tissues. Immune suppressive small molecule protein-based therapeutics targeting anti-host are currently used for GVHD prophylaxis treatment. Even with these therapies, aGVHD progresses to life-threatening steroid-refractory (SR-aGVHD) in up 50% cases risk factor the subsequent development debilitating chronic...
Cross-presentation initiates immune responses against tumors and viral infections by presenting extracellular antigen on MHC I to activate CD8+ T cell-mediated cytotoxicity. In vitro studies in dendritic cells (DCs) established SNARE protein SEC22B as a specific regulator of cross-presentation. However, the vivo contribution cross-presentation has not been tested. To address this, we generated DC-specific Sec22b knockout (CD11c-Cre Sec22bfl/fl) mice. Contrary paradigm, SEC22B-deficient DCs...
Neurotropic alphaviruses such as western, eastern, and Venezuelan equine encephalitis viruses cause serious potentially fatal central nervous system infections in humans are high-priority potential bioterrorism agents. There currently no widely available vaccines or licensed therapies for these virulent pathogens. To identify novel antiviral drugs, we developed a cell-based assay with western virus replicon that expresses luciferase reporter gene screened small molecule diversity library of...
ABSTRACT Cell-intrinsic innate immune responses mediated by the transcription factor interferon regulatory 3 (IRF-3) are often vital for early pathogen control, and effective in neurons may be crucial to prevent irreversible loss of these critical central nervous system cells after infection with neurotropic pathogens. To investigate this hypothesis, we used targeted molecular genetic approaches cultured study cell-intrinsic host defense pathways primarily using alphavirus western equine...
Allogeneic hematopoietic cell transplantation (allo-HCT) through its graft-versus-tumor (GVT) effects is a curative therapy against many hematological malignancies. However, GVT linked to harmful graft-versus-host disease (GVHD) after allo-HCT. Both and GVHD require allogeneic T responses, which an energetically costly process that causes oxidative stress. Sirtuin 3 (SIRT3), mitochondrial histone deacetylase (HDAC), plays important role in cellular processes inhibition of reactive oxygen...
A potent graft-versus-leukemia (GVL) response is crucial in preventing relapse, the major impediment to successful allogeneic hematopoietic cell transplantation (HCT). In preclinical studies, type 1 interferon (IFN-α) enhanced cross-presentation of leukemia-specific antigens by CD8α dendritic cells (DCs) and amplified GVL. This observation was translated into a proof-of-concept phase 1/2 clinical trial with long-acting IFN-α (pegylated [pegIFNα]) patients undergoing HCT for high-risk acute...
Corticosteroids are the first line therapy for acute graft-versus-host disease (GVHD). However, outcome of steroid refractory GVHD (SR-GVHD) is poor due to a lack effective treatments. The development therapies SR-GVHD limited by an incomplete understanding its pathophysiology partly because absence clinically relevant animal models SR-GVHD. Here we addressed need model developing both MHC matched multiple minor histocompatibility antigens (miHAs) mismatched and haploidentical murine We...
T cell–mediated responses are dependent on their secretion of key effector molecules. However, the critical molecular determinants these proteins largely undefined. Here, we demonstrate that cell activation increases trafficking via ER-to-Golgi pathway. To study functional role this pathway, generated mice with a cell–specific deletion in SEC23B, core subunit coat protein complex II (COPII). We found SEC23B critically regulated secretome following activation. SEC23B-deficient cells exhibited...
Abstract Autophagy is a vital cellular process whose role in T immune cells poorly understood, specifically, its regulation of allo-immunity. Stimulation wild-type vitro and vivo with allo-antigens enhances autophagy. To assess the relevance autophagy to T-cell allo-immunity, we generated T-cell–specific Atg5 knock-out mice. Deficiency ATG5-dependent reduced proliferation increased apoptosis following allo-stimulation. The absence ATG5 allo-stimulated enhanced their ability release effector...
LncRNAs are differentially expressed by allogeneic antigen-stimulated T cells, and Linc00402 regulates cells.