About

Michael Tranter, PhD, is an Associate Professor in the Department of Molecular Medicine and Therapeutics at Ohio State College of Medicine. His research focuses on understanding the molecular mechanisms of post-transcriptional gene regulation that drive cardiometabolic diseases. His lab has demonstrated a functional role for the RNA binding protein HuR in the pathophysiology of cardiac remodeling, acting in both myocytes and fibroblasts. Additionally, his work has contributed to the field of adipose tissue biology, particularly in understanding how disruptions in adipose tissue homeostasis impact cardiac physiology. Dr. Tranter's research employs multi-disciplinary, mechanism-focused translational systems physiology approaches using both mouse and human tissues. His ongoing projects include studying pathological left ventricular cardiac hypertrophy and fibrosis leading to heart failure, calcium-mediated thermogenic metabolism in brown adipocytes, and adipose tissue-mediated endocrine effects on cardiac physiology. He earned his PhD in Molecular Pharmacology from the University of Cincinnati, College of Medicine, and his BS in Molecular Biology from Rose-Hulman Institute of Technology.

Research topics

• Internal medicine
• Endocrinology
• Medicine
• Biology
• Genetics
• Pharmacology
• Immunology
• Biochemistry
• Cardiology

Selected publications

• Pulmonary fibroblast activation during Aspergillus fumigatus infection enhances lung defense via immunomodulation and tissue remodeling

  Nature Communications · 2026-03-31

  articleOpen access

  Aspergillus fumigatus is the etiologic agent of invasive aspergillosis, a life-threatening fungal pneumonia initiated by the inhalation of conidia into the lung. If the conidia are not cleared, they secrete large quantities of hydrolytic enzymes and toxins as they grow, causing extensive pulmonary damage. Fibroblasts are central mediators of tissue repair in many organs, but their functional response to pulmonary damage caused by A. fumigatus remains unexplored. Here, we employ cell lineage tracing, targeted cell ablation, and single-cell RNA sequencing to monitor fibroblast dynamics upon exposure to A. fumigatus in immunocompetent and immunosuppressed hosts. We find that a subset of pulmonary fibroblasts becomes activated in an immunocompetent host following a challenge with A. fumigatus conidia, initiating a gene expression program with acquired immunomodulatory properties and enhanced extracellular matrix-secreting capacity. Remarkably, targeted ablation of fibroblasts expressing the profibrotic activation marker periostin shows that invasive A. fumigatus infection accelerates in the absence of periostin lineage cells, accompanied by aberrant immune infiltration, tissue damage and severe alveolar hemorrhage. These findings uncover a protective immunomodulatory role for fibroblasts in limiting A. fumigatus-induced pulmonary injury and emphasize the importance of the pulmonary stroma in host defense against this invasive fungal infection.

  PublisherOA PDFDOI

• Systemic Consequences of Chronic Ethanol Intake: From Microbiome Shifts to Metabolic Impairment

  Comprehensive physiology · 2026-03-26

  articleOpen access

  Chronic ethanol (EtOH) consumption is a major contributor to multi-organ dysfunction, yet its systemic effects remain incompletely understood. To address this, we utilized a physiologically relevant long-term mouse model, administering 20% EtOH in drinking water for 60 weeks, to investigate the integrated consequences of chronic exposure. EtOH-consuming mice (0.4-0.5 mL/day) exhibited > 30% reductions in chow and fluid intake, resulting in a 12% decrease in total caloric intake compared to controls (p < 0.001). Body mass remained similar until Week 52, after which EtOH-treated mice had lower body mass due to reductions in both lean and fat mass (p ≤ 0.004). Functional assessments revealed impaired treadmill endurance (-17%) and grip strength (-11%) (p ≤ 0.037), while motor coordination remained unaffected (p = 0.203). Chronic EtOH exposure significantly altered gut microbiota composition, reducing Lactobacillus and enriching Faecalibaculum, Clostridium, and Bifidobacterium at the genus level. These changes were accompanied by marked depletion of short-chain fatty acids (p ≤ 0.05). Indirect markers of gut permeability (serum LPS & zonulin) and liver injury (serum ALT & AST, hepatic amyloid content) were elevated, alongside increased total cholesterol and > 62% upregulation of hepatic TNFα, IL-6 & serum amyloid A (p ≤ 0.046). EtOH also induced dyslipidemia and glucose intolerance (p ≤ 0.041), although transcriptomic changes in white adipose tissue were minimal despite elevated free fatty acids. In conclusion, chronic EtOH consumption disrupts energy balance, compromises gut barrier integrity, and impairs hepatic metabolism, collectively driving systemic and metabolic dysfunction. These findings underscore the gut-liver axis as a key mediator of EtOH-induced pathology and highlight the gut microbiome as a promising therapeutic target.

  PublisherDOI

• PAR2 (Protease-Activated Receptor 2) Deficiency Attenuates Atherosclerosis in Mice

  UNC Libraries · 2026-03-20

  articleOpen access

  OBJECTIVE: PAR2 (protease-activated receptor 2)-dependent signaling results in augmented inflammation and has been implicated in the pathogenesis of several autoimmune conditions. The objective of this study was to determine the effect of PAR2 deficiency on the development of atherosclerosis. APPROACH AND RESULTS: PAR2 mRNA and protein expression is increased in human carotid artery and mouse aortic arch atheroma versus control carotid and aortic arch arteries, respectively. To determine the effect of PAR2 deficiency on atherosclerosis, male and female low-density lipoprotein receptor-deficient (<em>Ldlr</em>^-/-) mice (8-12 weeks old) that were <em>Par2</em>^+/+ or <em>Par2</em>^-/- were fed a fat- and cholesterol-enriched diet for 12 or 24 weeks. PAR2 deficiency attenuated atherosclerosis in the aortic sinus and aortic root after 12 and 24 weeks. PAR2 deficiency did not alter total plasma cholesterol concentrations or lipoprotein distributions. Bone marrow transplantation showed that PAR2 on nonhematopoietic cells contributed to atherosclerosis. PAR2 deficiency significantly attenuated levels of the chemokines <em>Ccl2</em> and <em>Cxcl1</em> in the circulation and macrophage content in atherosclerotic lesions. Mechanistic studies using isolated primary vascular smooth muscle cells showed that PAR2 deficiency is associated with reduced <em>Ccl2</em> and <em>Cxcl1</em> mRNA expression and protein release into the supernatant resulting in less monocyte migration. CONCLUSIONS: Our results indicate that PAR2 deficiency is associated with attenuation of atherosclerosis and may reduce lesion progression by blunting <em>Ccl2</em>- and <em>Cxcl1</em>-induced monocyte infiltration.

  PublisherDOI

• Wnt1-Inducible Signaling pathway Protein-1 (WISP1) A New Mediator for Fibroblast Activities

  Journal of Molecular and Cellular Cardiology Plus · 2025-06-01

  articleOpen accessSenior author
  PublisherDOI

• <scp>HuR</scp> inhibition reduces post‐ischemic cardiac remodeling by dampening myocyte‐dependent inflammatory gene expression and the innate immune response

  The FASEB Journal · 2025-03-14 · 6 citations

  articleOpen accessSenior authorCorresponding

  The RNA-binding protein human antigen R (HuR) has been shown to reduce cardiac remodeling following both myocardial infarction and cardiac pressure overload, but the full extent of the HuR-dependent mechanisms within cells of the myocardium has yet to be elucidated. Wild-type mice were subjected to 30 min of cardiac ischemia (via LAD occlusion) and treated with a novel small molecule inhibitor of HuR at the time of reperfusion, followed by direct in vivo assessment of cardiac structure and function. Direct assessment of HuR-dependent mechanisms was done in vitro using neonatal rat ventricular myocytes (NRVMs) and bone marrow-derived macrophages (BMDMs). HuR activity is increased within 2 h after ischemia/reperfusion (I/R) and is necessary for early post-I/R inflammatory gene expression in the myocardium. Despite an early reduction in inflammatory gene expression, HuR inhibition has no effect on initial infarct size at 24 h post-I/R. However, pathological remodeling is reduced with preserved cardiac function at 2 weeks post-I/R upon HuR inhibition. RNA sequencing analysis of gene expression in NRVMs treated with LPS to model damage-associated molecular pattern (DAMP)-mediated activation of toll-like receptors (TLRs) demonstrates a HuR-dependent regulation of pro-inflammatory chemokine and cytokine gene expression in cardiomyocytes. Importantly, we show that conditioned media transfer from NRVMs pre-treated with HuR inhibitor loses the ability to induce inflammatory gene expression and M1-like polarization in bone marrow-derived macrophages (BMDMs) compared to NRVMs treated with LPS alone. Functionally, HuR inhibition reduces macrophage infiltration to the post-ischemic myocardium in vivo. Additionally, we show that LPS-treated NRVMs induce the migration of peripheral blood monocytes in a HuR-dependent endocrine manner. These studies demonstrate that HuR is necessary for early pro-inflammatory gene expression in cardiomyocytes following I/R injury that subsequently mediates monocyte recruitment and macrophage activation in the post-ischemic myocardium.

  PublisherOA PDFDOI

• Translational link between gene expression in human subcutaneous adipose tissue and cardiac function

  Journal of Molecular and Cellular Cardiology Plus · 2025-06-01

  articleOpen accessSenior author
  PublisherDOI

• <i>MCM2</i> mediates post-MI cardioprotection by promoting the pro-angiogenic cardiosome signaling

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-12-17 · 1 citations

  preprintOpen access

  Abstract Background In the past decade, induced cardiac rejuvenation has emerged as a leading approach to repair cardiac injury. Recent studies demonstrate that promoting cell cycle reentry in adult cardiomyocytes (CM) enhances cardiac rejuvenation by influencing paracrine signaling. We previously demonstrated that the inhibition of two cell cycle inhibitors, Retinoblastoma 1 (Rb1) and Meis homeobox 2 (Meis2), in the adult CM enhances angiogenesis and cardiac function following ischemic injury, but the underlying mechanisms have yet to be elucidated. The goal of this study is to determine the mechanisms by which inhibition of Rb1 and Meis2 promotes cardiac rejuvenation in a mouse model of myocardial infarction. Methods Myocardial infarction was induced in adult C57/Bl6 mice via permanent LAD occlusion followed by direct injection of either control or Rb1 + Meis2 siRNA cocktail to the ischemic myocardium. MCM2 overexpression done via direct myocardial injection of an MCM2- plasmid DNA expression cassette. Cardiac function and LV wall motion was assessed via echocardiography, and fibrosis and CM hypertrophy were assessed via histology. RNA-sequencing was performed on isolated adult murine CMs with siRNA-mediated Rb1 + Meis2 knockdown to delineate the downstream mechanisms. Further identification of Rb1, Meis2, and MCM2 -dependent mechanisms were done using in vitro techniques in isolated CMs and HUVEC cells. Results We show that siRNA-mediated knockdown of Rb1 and Meis2 in vivo reduces pathological LV remodeling and preserves cardiac structure and function in adult mouse hearts post-MI. RNA-seq analyses revealed MCM2 as a potential downstream target of Rb1/Meis2 to enhance protective paracrine signaling in primary adult CMs. Indeed, re-expression of MCM2, which is developmentally lost from neonatal to adult CM in the heart, improves cardiac function and LV wall motion while reducing myocyte hypertrophy and fibrotic scar size post-MI. Mechanistically, re-expression of MCM2 promotes the secretion of pro- angiogenic factors from adult CM, and transfer of conditioned media from MCM2 expressing CM induced vasculogenesis in HUVEC cells. Proteomic analysis of the MCM2 interactome confirmed a significant enrichment of angiogenic mediators and suggests an MCM2 -dependent protein packaging of pro- angiogenic factors in CM-derived small extracellular vesicles (cardiosomes). Conclusion Re-expression of MCM2 in adult CM promotes the secretion of pro-angiogenic cardiosomes that induce paracrine revascularization of endothelial cells and mitigates cardiac injury post-MI. SUMMARY DIAGRAM

  PublisherOA PDFDOI

• Wnt1-Inducible Signaling Pathway Protein-1 (WISP1) Modulation of Cardiac Fibroblasts Activity

  Journal of Pharmacology and Experimental Therapeutics · 2024-05-13

  articleSenior author
  PublisherDOI

• HuR-dependent expression of RyR2 contributes to calcium-mediated thermogenesis in brown adipocytes

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-10-24

  preprintOpen accessSenior authorCorresponding

  Abstract Several uncoupling protein 1 (UCP1)-independent thermogenic pathways have been described in thermogenic adipose tissue, including calcium-mediated thermogenesis in beige adipocytes via sarco/endoplasmic reticulum ATPase (SERCA). We have previously shown that adipocyte-specific deletion of the RNA binding protein human antigen R (HuR) results in thermogenic dysfunction independent of UCP1 expression. RNA sequencing revealed the downregulation of several genes involved in calcium ion transport upon HuR deletion. The goal of this work was to define the HuR-dependent mechanisms of calcium driven thermogenesis in brown adipocytes. We generated (BAT)-specific HuR-deletion (BAT-HuR -/- ) mice and show that their body weight, glucose tolerance, brown and white adipose tissue weights, and total lipid droplet size were not significantly different compared to wild-type. Similar to our initial findings in Adipo-HuR -/- mice, mice with BAT-specific HuR deletion are cold intolerant following acute thermal challenge at 4°C, demonstrating specificity of acute HuR-dependent thermogenesis to BAT. We also found decreased expression of ryanodine receptor 2 (RyR2), but no changes in RyR2, SERCA1, SERCA2, or UCP1 expression, in BAT from BAT-HuR -/- mice. Next, we used Fluo-4 calcium indicator dye to show that genetic deletion or pharmacological inhibition of HuR blunts the increase in cytosolic calcium concentration in SVF-derived primary brown adipocytes. Moreover, we saw a similar blunting in β-adrenergic-mediated heat generation, as assessed by ERtherm AC fluorescence, in SVF-derived brown adipocytes following HuR inhibition or deletion. Mechanistically, we show that HuR directly binds and reduces the decay rate of RyR2 mRNA in brown adipocytes, and stabilization of RyR2 via S107 rescues β-adrenergic-mediated cytosolic calcium increase and heat generation in HuR deficient brown adipocytes. In conclusion, our results suggest that HuR-dependent control of RyR2 expression plays a significant role in the thermogenic function of brown adipose tissue through modulation of SR calcium cycling.

  PublisherOA PDFDOI

• Pulmonary fibroblast activation during <i>Aspergillus fumigatus</i> infection enhances lung defense via immunomodulation and tissue remodeling

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-12-20

  preprintOpen access

  ABSTRACT Aspergillus fumigatus is the etiologic agent of invasive aspergillosis, a life- threatening fungal pneumonia that is initiated by the inhalation of conidia (spores) into the lung. If the conidia are not cleared, they secrete large quantities of hydrolytic enzymes and toxins as they grow, resulting in extensive damage to pulmonary tissue. Stromal fibroblasts are central responders to tissue damage in many organs, but their functional response to pulmonary injury caused by A. fumigatus has not been explored. In this study, we employed cell lineage tracing, targeted cell ablation, and single-cell RNA sequencing to monitor the dynamics of fibroblast behavior upon exposure to A. fumigatus in both immunocompetent and immunosuppressed hosts. The results demonstrate that a subset of pulmonary fibroblasts becomes activated in an immunocompetent host in response to a challenge with A. fumigatus conidia, acquiring a gene expression program reflecting the acquisition of new immunomodulatory properties as well as enhanced extracellular matrix (ECM)-secreting ability. Remarkably, through targeted ablation of fibroblasts that express the profibrotic activation marker periostin, we demonstrate that the progression of an invasive A. fumigatus infection in an immunosuppressed host is accelerated by the absence of periostin lineage cells and is accompanied by severe alveolar hemorrhage and angioinvasion. These findings uncover a novel protective role for fibroblasts in limiting the severity of A. fumigatus -induced pulmonary injury and emphasize the importance of the pulmonary stroma in host defense against this invasive fungal infection.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HL132111

  NIH · $1.8M · 2022

Frequent coauthors

• Sarah Anthony

  The Ohio State University

  45 shared

• Xiaoping Ren

  Guangxi University of Chinese Medicine

  22 shared

• Samuel Slone

  University of Cincinnati Medical Center

  22 shared

• Jack Rubinstein

  University of Cincinnati Medical Center

  22 shared

• A. Phillip Owens

  University of Cincinnati Medical Center

  21 shared

• Michelle L. Nieman

  University of Cincinnati Medical Center

  18 shared

• Adrienne Guarnieri

  University of Cincinnati Medical Center

  18 shared

• W. Keith Jones

  Loyola University Chicago

  17 shared

Education

• Post-Doctoral Fellowship, Pharmacology

  University of Cincinnati College of Medicine

  2012

• Ph.D., Molecular, Cellular, and Biochemical Pharmacology

  University of Cincinnati College of Medicine

  2010

• B.S.

  Rose Hulman Institute of Technology

  2004