The Pulmonary Division maintains a variety of research initiatives from basic science to large-scale clinical and multidisciplinary research. Many of these studies are open to normal volunteers as well as patients with diseases outlined below which are actively being investigated.

Asthma Clinical Research Center Indiana University is home to an American Lung Association sponsored Asthma Clinical Research Center (ACRC). This center is currently conducting several clinical research protocols in patients with asthma and maintains a large patient database for future studies. Michael Busk, M.D., MPH

Center for Immunobiology The Center for Immunobiology at the Indiana University School of Medicine is committed to be a worldwide leader in the investigation of the immunological basis of disease. David Wilkes, M.D. - Director Janice Blum, Ph.D. - Co-Director

Emphysema / Chronic Obstructive Pulmonary Disease (COPD) Our laboratory investigates the pathogenesis of and repair strategies for the lung injury that occurs in emphysema (COPD). Primarily caused by cigarette smoking, COPD is now the 3rd cause of mortality in the US. For the past decades the predominant paradigm in the emphysema research was that of a protease /antiprotease imbalance. Our work contributed to solidify the notion that cell death of structural components of the lung alveolus, epithelial and endothelial cells is sufficient to cause emphysema. We demonstrated that modifications in the abundance of the signaling sphingolipid ceramide trigger a cascade of events that culminates in emphysema-like disease in animals. To rebalance the sphingolipid homeostasis, we recently demonstrated that augmentation of endothelial pro-survival signaling with sphingosine-1 phosphate agonists is effective in preventing lung structural cell apoptosis and airspace enlargement. In addition, our laboratory studies mechanisms by which the anti-protease alpha 1 antitrypsin (A1AT) protects the lung. We showed that lung endothelial cells take up A1AT, and that A1AT has an anti-apoptotic function in lung vascular cells, which improved our understanding of emphysema pathogenesis and may expand the applications for A1AT therapies. The main established, ongoing projects in the lab are to understand the role and application of sphingolipid signaling in COPD and to investigate the mechanisms by which A1AT has direct cellular protective mechanisms in COPD, with the goal of enhancing its therapeutic application and effectiveness. In addition, we have several ongoing collaborative projects in the lab: 1) with Matthias Clauss, PhD, we study the mechanistic link between apoptosis and inflammation in the lung via the cytokine EMAPII; 2) with Keith March, MD PhD, we investigate the application of adult adipose progenitor cells as regenerative anti-apoptotic therapy in experimental emphysema; 3) with Hal Broxmeyer we investigate the effect of cigarette smoking on hematopoiesis and crosstalk of bone marrow with the lung in COPD; 4) using our expertise in vascular lung biology, with Tim Lahm, MD, we investigate of hypoxic PH both in vivo, in rats and mice, and in vitro, in primary lung endothelial cells; 5) since mechanistic investigation of emphysema and PH requires sophisticated lung function assessment and modern imaging, we implemented a novel intravital two photon excitation microscopy model of the lung in intact rodents, via close collaboration with the IU Biologic Microscopy Core and Robert G. Presson, MD. Irina Petrache, M.D.

Histoplasmosis Basic science and translational research is being conducted to assess the host response to histoplasmosis, a common pulmonary infection in the Midwest. Additionally, the effect of anti-inflammatory treatments (specifically, anti-cytokine therapy) on pulmonary and systemic immune responses against histoplasmosis is being evaluated. Human subjects are being recruited for these studies. Chadi Hage, M.D.

Immunologic Lung Disease Research David S. Wilkes, M.D. - UIP Homer Twigg, M.D. - Immune response in the lung

Interventional Pulmonology Praveen Mathur, M.B.B.S. Frank Sheski, M.D. Robert W. Weller, Jr., M.D.

Intensive Care Indiana University recently became a charter member of the Midwest Critical Care Consortium, a group of institutions conducting studies in the ICU setting. Current areas of interest include physician staffing in the ICU, use of semi-invasive devices, the effects of neuromuscular weakness on ICU outcomes, and the use of bundled protocols (i.e. sepsis treatment, prevention of nosocomial pneumonia) in patient care in the ICU. Karen Wolf, M.D. Michael Ober, M.D.

Lung Immunity in HIV Infection Basic science and translational research is being conducted to assess lung immunity in HIV infection. A current major focus is on pulmonary immune reconstitution in patients starting highly active antiretroviral therapy. HIV-infected subjects, both those starting antiretroviral therapy as well as those already on treatment, are recruited for these studies. Homer Twigg, M.D. Chadi Hage, M.D.

Lung Transplantation Basic scientific research is being performed to investigate mechanisms behind lung transplant rejection. Several animal models are utilized in this research. In addition, clinical samples from patients who have undergone lung transplantation are studied to provide a translational research link between the bench and bedside. David Wilkes, M.D.

Pulmonary Hypertension Research is being conducted investigating mechanisms and therapeutic interventions in acute hypoxic pulmonary vasoconstriction and hypoxic pulmonary hypertension (PH). In particular, we are interested in the effects of estrogens and selective estrogen receptor agonists on hypoxia-induced endothelial cell activation and pulmonary vascular remodeling (e.g. growth factor and cytokine production, and proliferation/apoptosis markers) and endotoxemia-induced pulmonary vascular dysfunction. This research is being pursued in isolated lung endothelial cells (in collaboration with Dr. Mircea Ivan, Division of Hematology/Oncology), in rat pulmonary artery rings, as well as in a rodent model of chronic hypoxic PH (in collaboration with Dr. Robert Presson, Dept. of Anesthesiology). Tim Lahm, M.D. Irina Petrache, M.D.

Sarcoidosis Research Basic science and translational research is being conducted to study the pathogenesis of sarcoidosis and pulmonary immune responses in patients with this disease. Additionally, the effect of anti-inflammatory treatments (specifically, anti-cytokine therapy) on pulmonary and systemic immune responses is being evaluated. Normal volunteers and subjects with sarcoidosis are recruited for these studies. For information on how to donate money for patient-oriented research in sarcoidosis, please contact Michelle Jones. Chadi Hage, M.D.

Sleep Medicine Sleep medicine emerged as a new discipline in medicine during the 1980's and 1990's. Recently, a team of investigators recognized the need for a comprehensive and multi-disciplinary approach to the practice and study of sleep and sleep disorders using the unique resources on the IUPUI campus. This program, which has now received funding from Indiana University (RIF), was developed by the Sleep Medicine Program and supported by a multidisciplinary team from the IUPUI campus. Collaborators include individuals from the School of Medicine (Neurology, Psychiatry, Otolaryngology, Gastroenterology, and Pulmonary), the School of Engineering & Technology (and the Biomedical Engineering Program), the School of Nursing, and the School of Dentistry. Michael Ober, M.D. Shalini Manchanda, M.B.B.S.