A5056559242- interferon and immune responses
- Tissue Engineering and Regenerative Medicine
- Cardiac Ischemia and Reperfusion
- Muscle Physiology and Disorders
- Caveolin-1 and cellular processes
- Cardiac Fibrosis and Remodeling
- Cellular transport and secretion
- Heme Oxygenase-1 and Carbon Monoxide
- Congenital heart defects research
- Virus-based gene therapy research
- Cancer Research and Treatments
- Ion channel regulation and function
- Immune Response and Inflammation
- Inflammasome and immune disorders
- SARS-CoV-2 and COVID-19 Research
- Cancer, Hypoxia, and Metabolism
- Hemoglobin structure and function
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Ion Channels and Receptors
- Erythrocyte Function and Pathophysiology
- Signaling Pathways in Disease
- Autophagy in Disease and Therapy
- RNA Interference and Gene Delivery
- Drug Transport and Resistance Mechanisms
University of Virginia
2023-2024
The Ohio State University Wexner Medical Center
2020-2024
The Ohio State University
2020-2023
Albany Medical Center Hospital
2015-2023
Lung Institute
2021
Johnson University
2006-2015
University of Louisville
2011-2015
Rutgers, The State University of New Jersey
2008-2015
Chinese Academy of Sciences
2004
Institute of Biophysics
2004
Defective membrane repair can contribute to the progression of muscular dystrophy. Although mutations in caveolin-3 (Cav3) and dysferlin are linked dystrophy human patients, molecular mechanism underlying functional interplay between Cav3 muscle physiology disease has not been fully resolved. We recently discovered that mitsugumin 53 (MG53), a muscle-specific TRIM (Tri-partite motif) family protein (TRIM72), contributes intracellular vesicle trafficking is an essential component machinery...
Recombinant human MG53 protein can increase membrane repair after injury in cells and reduce pathology animal models of muscle muscular dystrophy.
Significance Measles virus (MeV) vaccine is one of the safest and most efficient vaccines with a track record in children. Here, we generated panel rMeV-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S antigens inserted near 3′ MeV genome. The rMeV expressing soluble stabilized, prefusion spike (preS) much more potent triggering SARS-CoV-2–specific neutralizing antibody than full-length candidate. A single dose rMeV-preS sufficient to induce high levels SARS-CoV-2...
Abstract Interferon‐induced transmembrane protein 3 (IFITM3) is an antiviral that alters cell membranes to block fusion of viruses. Conflicting reports identified opposing effects IFITM3 on SARS‐CoV‐2 infection cells, and its impact viral pathogenesis in vivo remains unclear. Here, we show knockout (KO) mice infected with experience extreme weight loss lethality compared mild wild‐type (WT) mice. KO have higher lung titers increases inflammatory cytokine levels, immune infiltration,...
Abstract Influenza virus activates cellular inflammasome pathways, which can be both beneficial and detrimental to infection outcomes. Here, we investigate the function of inflammasome-activated, pore-forming protein gasdermin D (GSDMD) during infection. Ablation GSDMD in knockout (KO) mice ( Gsdmd −/− ) significantly attenuates influenza virus-induced weight loss, lung dysfunction, histopathology, mortality compared with wild type (WT) mice, despite similar viral loads. Infected exhibit...
Membrane recycling and remodeling contribute to multiple cellular functions, including cell fusion events during myogenesis. We have identified a tripartite motif (TRIM72) family member protein named MG53 defined its role in mediating the dynamic process of membrane exocytosis striated muscle. is muscle-specific that contains TRIM at amino terminus SPRY carboxyl terminus. Live imaging green fluorescent protein-MG53 construct cultured myoblasts showed although no transmembrane segment it...
Muscular dystrophies (MDs) are caused by genetic mutations in over 30 different genes, many of which encode for proteins essential the integrity muscle cell structure and membrane. Their deficiencies cause vulnerable to mechanical biochemical damages, leading membrane leakage, dystrophic pathology, eventual loss cells. Recent studies report that MG53, a muscle-specific TRIM-family protein, plays an role sarcolemmal repair. Here, we show systemic delivery overexpression human MG53 gene...
Abstract TRIM family proteins play integral roles in the innate immune response to virus infection. MG53 (TRIM72) is essential for cell membrane repair and believed be a muscle-specific protein. Here we show human macrophages express MG53, protein expression reduced following Knockdown of leads increases type I interferon (IFN) upon knockout mice infected with influenza comparable titres wild mice, but display increased morbidity accompanied by more accumulation CD45+ cells elevation IFNβ...
Repair of injury to the plasma membrane is an essential mechanism for maintenance cellular homeostasis and integrity that involves coordinated movement intracellular vesicles sites facilitate patch formation. We have previously identified MG53 as component cell repair machinery. In order translocate sites, motor proteins must be involved. Here, we show nonmuscle myosin type IIA (NM-IIA) interacts with regulate vesicle trafficking during repair. cells are deficient NM-IIA expression, cannot...
MG53 is a member of the TRIM protein family that predominantly expressed in striated muscles and participates cell membrane repair. Controversy exists regarding MG53’s role insulin signaling manifestation diabetes. We generated db/db mice with either whole-body ablation or sustained elevation bloodstream order to evaluate physiological function To quantify amount circulation, we developed monoclonal antibody against high specificity. Western blot using this revealed lower no change serum...
The regenerative potential of c-kit(+) cardiac stem cells (CSCs) is severely limited by the poor survival after transplantation in infarcted heart. We have previously demonstrated that preconditioning human CSCs (hCSCs) with heme oxygenase-1 inducer, cobalt protoporphyrin (CoPP), has significant cytoprotective effects vitro. Here, we examined whether hCSCs CoPP enhances CSC and improves function a model myocardial infarction induced 45-minute coronary occlusion 35-day reperfusion...
Aging is associated with chronic oxidative stress and inflammation that affect tissue repair regeneration capacity. MG53 a TRIM family protein facilitates of cell membrane injury in redox-dependent manner. Here, we demonstrate the expression was reduced failing human hearts aged mouse hearts, concomitant elevated NF-κB activation. We evaluated safety efficacy longitudinal, systemic administration recombinant (rhMG53) mice. Echocardiography pressure-volume loop measurements revealed...
Cardiac dysfunction is a common complication of severe influenza virus infection, but whether this occurs due to direct infection cardiac tissue or indirectly through systemic lung inflammation remains unclear. To test the etiology aspect disease, we generated novel recombinant heart-attenuated via genome incorporation target sequences for miRNAs expressed in cardiomyocytes. Compared with control virus, mice infected miR-targeted had significantly reduced heart viral titers, confirming...
Zinc is an essential trace element that participates in a wide range of biological functions, including wound healing. Although Zn2+ deficiency has been linked to compromised healing and tissue repair human diseases, the molecular mechanisms underlying Zn2+-mediated remain unknown. Our previous studies established MG53, TRIM (tripartite motif) family protein, component cell membrane machinery. Domain homology analysis revealed MG53 contains two Zn2+-binding motifs. Here, we show binding...
Studies on cardiac progenitor cells (CPCs) and their derived exosomes therapeutic potential have demonstrated only modest improvements in function. Therefore, there is an unmet need to improve the efficacy of CPCs attain clinically relevant improvement The hypothesis this project assess from human (hCPCs) cultured under normoxia (21% O2), physoxia (5% O2) hypoxia (1% conditions. hCPCs were characterized by immunostaining CPC-specific markers (NKX-2.5, GATA-4, c-kit). Cell proliferation cell...
Ubiquitin carboxyl-terminal esterase L1 (UCHL1) has been thought to be a neuron specific protein and shown play critical roles in Parkinson's Disease stroke via de-ubiquiting stabilizing key pathological proteins, such as α-synuclein. In the present study, we found that UCHL1 was significantly increased both mouse human cardiomyocytes following myocardial infarction (MI). When LDN-57444, pharmacological inhibitor of UCHL1, used treat mice subjected MI surgery, administration LDN-57444...
Abstract Human cardiac stem/progenitor cells (hCPCs) may serve in regenerative medicine to repair the infarcted heart. However, this approach is severely limited by poor survival of donor cells. Recent studies suggest that mammalian globin cytoglobin (CYGB) regulates nitric oxide (NO) metabolism and cell death. In present study, we found CYGB expressed hCPCs. Through molecular approaches aimed at increasing or decreasing expression hCPCs, functions as a pro-survival factor response oxidative...
Mitsugumin 53 (MG53) participates in the membrane repair of various cells, and skeletal muscle is major tissue that expresses MG53. Except for regulatory effects MG53 on SERCA1a, role(s) unique functions such as contraction have not been well examined. Here, a new MG53-interacting protein, Orai1, identified muscle. To examine functional relevance MG53-Orai1 interaction, was over-expressed mouse primary or C2C12 myotubes properties were examined using cell physiological biochemical...
The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome 2 (SARS-CoV-2) has led to dramatic economic and health burdens. Although the worldwide SARS-CoV-2 vaccination campaign begun, exploration other vaccine candidates is needed due uncertainties with approved vaccines, such as durability protection, cross-protection against variant strains, costs long-term production storage. In this study, we developed a methyltransferase-defective...
In cells undergoing apoptosis, a 22-amino-acid presenilin-2-loop peptide (PS2-LP, amino acids 308–329 in presenilin-2) is generated through cleavage of the carboxyl-terminal fragment presenilin-2 by caspase-3. The impact PS2-LP on progression however, not known. Here we show that potent inducer mitochondrial-dependent cell death pathway when transduced as fusion protein with HIV-TAT. Biochemical and functional studies demonstrate TAT-PS2-LP can interact inositol 1,4,5-trisphosphate receptor...