John Osterholzer, M.D.

Professor of Internal Medicine
Department of Medicine, Division of Pulmonary and Critical Care.

Biography

I was granted my undergraduate degree at the University of Michigan (B.S.; Biology) in 1994 having also completed an Undergraduate Honors Thesis in the field of Tumor Immunotherapy (Mentor Bernard Fox, Ph.D.). I obtained my Medical Degree from the University of Michigan Medical School in 1999 having also completed additional graduate school classes and research rotations through the Department of Pathology (Mentor James Mule, Ph.D.). I completed Residency Training in Internal Medicine at the University of Michigan Health System from 1999-2002. From 2002-2003 I completed a postdoctoral fellowship in Pulmonary Immunology funded by the Department of Veterans Affairs Research Enhancement Program (Mentor Jeffrey Curtis, M.D.). Thereafter, I completed a Pulmonary and Critical Care Fellowship Training Program (2003-2006) with additional primary research training in the field of Pulmonary Immunology (Mentor Galen Toews, M.D.). Since 2006 I have been a Faculty Member in the Division of Pulmonary and Critical Care Medicine at the University of Michigan Health System and the Ann Arbor VA Health System. I was appointed Assistant Professor in the Department of Internal Medicine and a Faculty Member in the Graduate Program in Immunology in 2010. I was promoted to Associate Professor in 2016 and have been the VA Ann Arbor Site Leader for the VA Post-Deployment Cardiopulmonary Evaluation Network since 2019.  I was promoted to Professor of Medicine in 2023.  Sources of research funding have included the Department of Veterans Affairs, National Institutes of Health, and the Department of Defense.

Research Interests

As a pulmonologist at the Ann Arbor VA Heatlh System, I am increasingly seeing younger patients experiencing chronic respiratory symptoms following exposures to airborne hazards (military burn pit smoke, sand and dust storms, particulate matter, sulfur dioxide, fuel fumes, etc.) during prior deployments to Iraq and Afghanistan. Abnormal histopathologic features identified on surgical lung biopsies confirm the presence of multi-compartmental lung epithelial injury, chronic inflammation, and fibrosis which has been defined as "Deployment Related Respiratory Disease" (DRRD). Our laboratory uses a variety of murine models that recapitulate features of DRRD to investigate basic interrelationships between damaged/apoptotic airway and alveolar epithelial cells, lung macrophages, and mesenchymal cells to elucidate critical cellular and molecular pathways that contribute to disease pathophysiology. Translational studies seek to identify new methods to diagnose and treat DRRD.

Our laboratory broadly investigates the pathophysiology of deployment related respiratory disease (DRRD). More specifically, we study interrelationships between damaged/apoptotic airway and alveolar epithelial cells, lung macrophages and other myeloid cells, and mesenchymal cells to identify critical cellular and molecular pathways that result in the pathologic changes which define DRRD. To recapitulate the small airways fibrosis observed in DRRD, we use a transgenic model of sustained targeted injury to murine club cells. Using this model, we have shown that alveolar macrophages are critically involved in promoting small airway fibrosis and that targeted depletion of lung macrophages is protective. Comparable studies using a transgenic model of sustained injury to type 2 alveolar epithelial cells indicates a pathologic role of lung macrophages in the development of the alveolar fibrosis observed in DRRD. Ongoing translational studies are evaluating whether treatment with azithromycin and/or anti-fibrotic drugs (including pirfenidone) modulate macrophage function and protect against lung fibrosis.

Our laboratory also partners with colleagues in the Department of Radiology and the Center for Molecular Imaging to investigate new lung imaging techniques that may improve our ability to diagnose DRRD non-invasively. Specific studies apply CT parametric response mapping and X-ray velocimetry to mice with sustained injury to either airway club cells or type 2 alveolar epithelial cells to better understand the effectiveness of these imaging techniques at identifying features of small airway and alveolar fibrosis.