OSU has a strong program of research in airway inflammation, including Cystic Fibrosis. Our research groups have contributed with seminal discoveries in the role of inhaled pollutants in the regulation of cellular metabolism, and immune responses. Research supported by NIH (R01), DoD., CF Foundation.

Image description: When inhaled, toxicants such as ozone, vehicle exhaust, silica dust, nanoparticles, particulate matter, and cigarette smoke are irritants that will stimulate the pulmonary immune response. This results in an increase in the production of pro-inflammatory cytokines and chemokines, increased epithelial permeability as well as increase immune cell recruitment. Once the pro-inflammatory cascade switches to pro-resolving, exposure to toxicants causes a decrease in anti-inflammatory cytokine release, an increase in apoptotic neutrophils, a decrease in efferocytic macrophages and an increase in aberrant lung repair. This figure has been generated by the Gowdy lab with Biorender.com

Airway and Environmental Lung Diseases faculty

Kymberly Gowdy, MS, PhD
Associate Professor, Division of Pulmonary, Critical Care and Sleep Medicine

Matthew Long, PhD
Assistant Professor

Yohannes A. Mebratu, DVM, MS. PhD
Pulmonary, Critical Care and Sleep Medicine

Critical illness syndromes, including lung inflammation, acute lung injury, ARDS, and sepsis, are major areas of basic, translational, and clinical research at OSU. Our investigators have contributed to the fundamental understanding of pathogenic mechanisms of viral and bacterial infection, inflammasome biology, ventilator induced lung injury, and ubiquitin proteosome system function in lung injury and sepsis. Translational studies utilize human samples from critically-ill patients to understand molecular mechanisms of disease and drug discovery to generate and study novel therapies. Among clinical researchers, our group boasts long-standing participation in major national network trials to study ARDS and sepsis, as well as investigator-initiated trials to evaluate novel therapeutics, the impact of oxygen titration protocols in the delivery of care for patients with respiratory failure, and the role of frailty in post-ICU outcomes. Research is supported by NIH (K08, K23, R01, R33, P01), American Lung Association (ALA).

Image description: The healthy lung functions to exchange oxygen and carbon dioxide gases at the alveoli, or tiny air sacs of the lung. Healthy alveoli are characterized by a thin respiratory epithelium, composed of type I and II pneumocytes covered by a layer of surfactant and juxtaposed to capillaries. The alveolar space is surveyed by resident alveolar macrophages. The alveolus may be damaged by a variety of insults, such as bacterial and viral infection, aspiration of oral secretions and gastric contents, or systemic infections including sepsis. During lung injury, inflammatory signaling molecules released by recruited immune cells result in damage to the alveolar-capillary membrane and influx of fluid, cellular debris, and immune cells into the alveolar space with subsequent impairment in gas exchange. The critical care group aims to understand the upstream regulators of these processes and trials novel therapeutics and interventions that may improve outcomes during lung injury and ARDS. Figure from “Pathogenesis of pneumonia and acute lung injury”, by Long et. Al., published in Clinical Science. Figure from “Pathogenesis of pneumonia and acute lung injury”, by Long et. Al., published in Clinical Science (London), 2022, and created by BioRender.com.

Critical Illness – Acute Respiratory Distress Syndrome and Sepsis faculty

Rama Mallampalli, MD
Chair, Department of Internal Medicine

Joshua Englert, MD
Associate Professor of Medicine
Associate Program Director, Pulmonary and Critical Care Medicine Fellowship Program

James Londino
Research Director, Center for Acute Lung Injury Research

Joseph Bednash, MD
Assistant Professor of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine

Ana L. Mora, MD
Division of Pulmonary, Critical Care and Sleep Medicine

Matthew Exline, MD
Physician, Clinical Professor of Internal Medicine

Sonal Pannu, MD, MBBS
Physician, Clinical Associate Professor of Internal Medicine

MuChun Tsai, MD

Nathan Brummel, MD
Physician, Associate Professor of Internal Medicine

Yohannes A. Mebratu, DVM, MS. PhD
Pulmonary, Critical Care and Sleep Medicine

John Christman, MD
Pulmonary Disease, Critical Care Medicine

OSU has an active research program in basic and translational research for Idiopathic Pulmonary Fibrosis (IPF) and other ILDs including sarcoidosis. Our investigators have contributed to define molecular mechanisms in the pathogenesis of ILDs and provid a better understanding of the fundamental mechanisms that underlie progressive fibrotic lung diseases, including the role of aging in the resilience to acute and chronic lung diseases, the regulation of fibroblast activation and survival, and the critical contributions of mitochondrial dysfunction. Clinical Research in ILD includes contributions to multiple industry sponsored trials, foundation registries, novel therapeutic trials in sarcoidosis. Research is supported by NIH (U54, U01, R01s), and Industry.

Image description: A proposed pathogenic model of Idiopathic Pulmonary Fibrosis in response to persistent injury and altered lung tissue repair. Schematic representation of lung cell types identified by scRNA-Sequencing in the alveoli of healthy and IPF lung Tissue. This figure was generated by the Mora & Rojas Labs using Biorender.com

Interstitial Lung Diseases faculty

Jeffrey Horowitz, MD, ATSF, FCCP
Division Director of Pulmonary, Critical Care and Sleep Medicine, Professor of Medicine

Mauricio Rojas, MD
Division of Pulmonary, Critical Care and Sleep Medicine

Ana L. Mora, MD
Division of Pulmonary, Critical Care and Sleep Medicine

Elliot Crouser, MD
Physician, Professor of Internal Medicine

Megan Ballinger, PhD
Associate Professor, Division of Pulmonary, Critical Care and Sleep Medicine

John Odackal, MD
Physician, Clinical Assistant Professor of Internal Medicine

Richard Nho, PhD
Associate Professor Internal Medicine, Research Associate Professor Medicine

Aging is a gradual and irreversible physiological process. It presents with declines in tissue and cell functions and significant increases in the risks of various diseases. Lung pathologies are no exception; the prevalence of lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) impacts the outcome of acute lung diseases such as acute respiratory distress syndrome (ARDS) and asthma. The lung is a highly heterogeneous organ with various cell types, subtypes, and structures that may contribute to the susceptibility and increased severity of lung diseases associated with aging. Our investigators actively contribute to NIH initiatives to understand this complexity and the correlation with age-related processes at the cellular and molecular levels and design geoscience-tailored approaches. Our collaborative work and unique expertise have created the first NIH-supported training program for fellows and postdocs on lung aging, preparing future generations of scientists and physicians for incoming challenges related to the new demographic patrons worldwide. Research is supported by NIH (U54, U01, R01), private foundations, and industry.

Image description: Biological lung aging is associated with a progressive decline in function, and age is a risk factor for acute and chronic lung diseases that are increasing in incidence and prevalence, including Chronic Obstructive Pulmonary Disease (COPD), Lung Cancer, Idiopathic Pulmonary Fibrosis (IPF), Acute Respiratory Distress Syndrome/ Acute Lung Injury (ARDS/ALI), asthma, pulmonary hypertension, pneumonia and others.

Lung Aging faculty

Ana L. Mora, MD
Division of Pulmonary, Critical Care and Sleep Medicine

Mauricio Rojas, MD
Division of Pulmonary, Critical Care and Sleep Medicine

Rama Mallampalli, MD
Chair, Department of Internal Medicine

Laszlo Farkas, MD
Associate Professor of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine

Bryan Whitson, MD, PHD
Physician, Professor of Surgery

Kymberly Gowdy, MS, PhD
Associate Professor, Division of Pulmonary, Critical Care and Sleep Medicine

Links for Aging Research:

• Midwest Aging Consortium: The Midwest Aging Consortium (MAC) provides a platform to promote and facilitate advances in aging research in the upper Mid-West. The 5th Annual MAC symposium is being conducted at The Ohio State University.
• TriState SenNet | University of Pittsburgh: The TriState SenNet Consortium seeks to comprehensively map senescent cells in the human heart and lung using a multi-modality approach involving various unbiased approaches on whole tissues, organ slices, and isolated cells in order to better characterize the senescent cell population and to identify the physiologically relevant triggers for senescent cell formation. The TriState SenNet Consortium is comprised of the University of Pittsburg, Carnegie Mellon University and the University of Rochester and The Ohio State University.

OSU has an active research program to study the pathobiology of pulmonary vascular diseases. This program dissects immune signaling, endosomal trafficking, endothelial biology, protein turnover, cardiovascular imaging, disease phenotyping, and right ventricular failure. Strong collaboration exists with the DHLRI and Heart Vascular Center investigators.

Image description: The Figure shows the pulmonary arteries (blood vessels in the lung) of animals with experimental pulmonary hypertension on the right after treatment with an experimental new drug. The red staining indicates the binding of Tomatolectin to delineate endothelial cells, which line the blood vessels from the inside. The green staining demonstrates the expression of Snail, a factor that promotes the transition of endothelial cells to mesenchymal cells. Blue staining indicates nuclear deoxyribonucleic acid. Figure from : J Clin Invest. 2024 Feb 1;134(3):e169441. doi: 10.1172/JCI169441. PMID: 38015641; PMCID: PMC10836802.

Pulmonary Vascular Biology and Disease faculty

Laszlo Farkas, MD
Associate Professor of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine

Jing Zhao, MD, PhD
Physiology and Cell Biology

Yutong Zhao, MD, PhD
Physiology and Cell Biology

The Sleep Medicine Research Program focuses on the cardiometabolic consequences of obstructive sleep apnea (OSA), a common condition that affects about a billion people worldwide. It includes both a basic science component examining the effects of hypoxia on adipose tissue biology as well as a clinical research program in sleep disorders. Obesity and OSA often coexist. Adipose tissue hypoxia leading to stabilization of hypoxia-inducible factor 1α (HIF-1α) serves as an early upstream initiator for adipose tissue dysfunction, characterized by macrophage infiltration, fibrosis, and insulin resistance.

Overexpression of a constitutively active form of Hif-1α in adipocytes results in adipose tissue dysfunction; conversely, selective genetic inhibition of Hif-1α in adipocytes results in reduced adipose tissue fibrosis and inflammation, and increased insulin sensitivity in mice. Furthermore, an Irak-M-dependent mechanism likely mediates obesity-related AT dysfunction in conjunction with Hif-1α upregulation. Whether the intermittent hypoxia, characteristic of OSA, contributes to adipose tissue dysfunction related to obesity remains to be explored. Examining these mechanistic pathways would be important in developing novel therapies for OSA in obese individuals.

Current clinical research includes leading a multi-center study examining whether microRNAs are clinically translatable biomarkers for OSA, measuring the efficacy of CPAP treatment, and predicting blood pressure treatment responses in patients with OSA. In addition, together with researchers belonging to the Sleep Apnea Global Interdisciplinary Consortium (SAGIC), we have identified three OSA clinical symptom subtypes across a worldwide sleep center population that has now been robustly validated in various community and clinic-based populations. These OSA symptom subtypes have recently been shown to predict OSA subjects who are at risk for developing cardiovascular events, a step towards personalized care for sleep apnea.

Funding: NIH, AASM Foundation, DOD 

Sleep Medicine Research Program faculty

Ulysses Magalang
Sleep Disorders Program