SCHOOL OF MEDICINE

Department of Medicine

Pulmonary, Critical Care, Sleep & Occupational Medicine

Research

Researchers in the Pulmonary Division pursue a variety of basic, translational and clinical research projects in the fields of Pulmonary and Critical Care Medicine. Research in the Division is conducted in facilities located on the campus of the Indiana University School of Medicine, its affiliated hospitals, and in collaboration with investigators at other academic institutions. Faculty and the research they conduct are recognized both nationally and internationally. Our research is funded by the National Institutes of Health, the Department of Veterans Affairs, non-profit organizations, foundations, and industry. Close collaborations exist with researchers in other Divisions and Centers in the Department of Medicine, as well as in the Basic Science Departments and in the Departments of Emergency Medicine, Pediatrics, and Physical Therapy. In addition, we collaborate extensively with investigators across the US.

The Division has a T32 Research Training Program that is administered jointly with the Pediatric Pulmonary Section. Research fellows have the opportunity to pursue additional training through the Clinical Investigation and Translational Education (CITE) Program or the Translational Science Education Program. We are holding a weekly Interdisciplinary Pulmonary Research Conference (R3/Walther Hall, room C303/305) during which physician scientists and basic science investigators from across campus present their ongoing work. A T32 Research Journal Club (held jointly with Pediatric Pulmonology) is held on a monthly basis

The Pulmonary Research Core is located in R3/Walther Hall. Resources in the Pulmonary Core include an RT-PCR machine, Thermal Cycler, Flow Cytometry equipment, an ECIS machine, Cytospin, Biosafety Cabinets and cell culture equipment, an Animal Procedure/Harvest Room, and a Flexivent PFT system. Additional specific resources are available in the individual PIs’ labs.

Investigators in the Pulmonary Division perform research in the following areas:

 


Cystic Fibrosis

Research is an integral part of the Adult Cystic Fibrosis Clinic at Indiana University. Our center is one of 82 sites that participates in the Cystic Fibrosis Foundation’s Therapeutic Development Network, the largest CF clinical trials network in the world. This robust network of centers works together under the guidance of the CF Foundation to perform high quality clinical trials in a broad range of therapeutic areas, including CFTR modulation, anti-inflammatories, anti-infectives, nutrition, and airway surface liquid hydration among others. Our center is currently active or in preparation for at least 6 different studies sponsored by this network, and with the CF Foundation pipeline only continuing to grow, we anticipate further growth in our clinical research activities in the upcoming year. In addition to research sponsored by the TDN, the Adult CF program also participates in independent investigation. Areas of our research focus include outcomes after transition from pediatric to adult CF care and vitamin D supplementation. Our research team consists of Dr. Cynthia Brown, the Adult CF Program Director, and Annette Hempfling, RN, lead Research Coordinator. Anyone with interest in CF research may contact us through our research coordinator at ahempfli@iu.edu.

Researcher(s):
Dr. Cynthia Brown


ICU Delirium

The Indiana University Delirium group has been conducting randomized clinical trials to reduce the burden of delirium in the ICU. These trials include both efficacy trials and pragmatic, effectiveness trials. In addition, a biorepository for ICU patients with delirium has been established to answer specific pathophysiological mechanisms predisposing to delirium.

Survivors of ICU are followed up at the Critical Care Recovery Center (CCRC), an ICU survivor clinic to improve long term cognitive, functional and psychological sequelae of critical illness

Collaborators: Local: Indiana University Center for Aging Research/Regenstrief Institute/Thoracic Surgery. National: Mayo Clinic, Vanderbilt University

Researcher(s):
Dr. Babar Khan


Lung Cancer

Researchers in the Pulmonary Division pursue NIH and VA-funded basic, translational and clinical projects studying a variety of aspects of non-small cell lung cancer (NSCLC). Active research areas are as follows:

  • mechanistic impact of DNA repair processes on the development of smoking-related NSCLC (Dr. Catherine Sears)

  • the role of DNA damage and repair in the lung microenvironment and their role in early stage lung cancer (Dr. Catherine Sears)

  • DNA damage response pathways effects on combination chemotherapeutic and radiation treatments cancer (Dr. Catherine Sears)

  • interplay of eicosanoid lipid mediators balancing pro-tumorigenic and anti-tumorigenic signals in NSCLC (Dr. Mark Geraci, Dr. Bob Stearman)

  • genetic polymorphisms within the prostacyclin synthase gene as disease modifiers in NSCLC (Dr. Mark Geraci, Dr. Bob Stearman)

  • Phase II/III clinical trial of iloprost and other FDA approved prostacyclin analogs for chemoprevention of lung squamous cell cancer (Dr. Mark Geraci, Dr. Bob Stearman)

Current methods for treating NSCLC result in poor survival. This illustrates the need to understand how chemotherapeutic drugs and radiation treatment affect lung cancer cells, why certain lung cancers respond to therapy, and to augment the efficacy of existing treatments as well as guide the development of new therapies. Our studies make use of in vitro methods and mouse models, including transgenic mouse models assessing the eicosanoid pathways. Cigarette smoke is the most common source of lung cancer carcinogens, so we use in vivo mouse models for these studies.

The Phase II/III clinical trial is being conducted in collaboration with Dr. Robert Keith (PI, Denver VA Hospital and the University of Colorado School of Medicine).

Researcher(s):
Dr. Mark Geraci
Dr. Catherine Sears
Dr. Bob Stearman


Lung Immunology and Lung Microbiome

Research in this area is performed by Dr. Homer Twigg. Dr. Twigg is a lung immunologist who has spent his career studying how HIV impairs pulmonary host immunity and leads to pulmonary complications seen in this patient population. This includes studies on how highly active antiretroviral therapy (HAART) affects pulmonary HIV viral loads and restores pulmonary immune responses and inflammation towards normal. More recently he has been studying the lung microbiome in HIV infection and in uninfected subjects. His lab has been at the forefront of describing the lung microbiome in both normal subjects and HIV-infected subjects. Dr. Twigg helped establish standards for acquiring lung samples for study, using appropriate controls, and performing analysis on complex data sets. His lab is now expanding its research focus to the lung virome, hypothesizing that viruses within the microbial milieu of the lung lead to chronic inflammation and some of the common chronic lung conditions like COPD, pulmonary hypertension, and cancer, both in HIV-infected and normal subjects.

Researcher(s):
Dr. Homer Twigg III


Pulmonary Hypertension

Researchers in the Pulmonary Division pursue NIH and VA-funded basic, translational and clinical projects in pulmonary vascular disease and right heart failure. Active research areas are as follows:

  • genetic polymorphisms within the PGI synthase gene as disease modifiers in pulmonary hypertension (Dr. Mark Geraci, Dr. Bob Stearman)

  • genomic analyses (gene expression and copy number) of human pulmonary hypertension lung (Dr. Mark Geraci, Dr. Bob Stearman)

  • long-term consequences of postnatal hyperoxic pulmonary vascular injury (Dr. Tim Lahm)

  • mechanisms of adaptive and maladaptive right ventricular remodeling in pulmonary hypertension (Dr. Tim Lahm)

  • novel genetic and genomic approaches to the study of human tissue samples in patients with pulmonary hypertension (Dr. Mark Geraci, Dr. Bob Stearman)

  • sex steroid signaling in the right ventricle and pulmonary vasculature in pulmonary hypertension (Dr. Tim Lahm)

In collaborations with Dr. Jeff Kline in the Department of Emergency Medicine, we study platelet function and right heart adaptation to acute and chronic pulmonary embolism. A collaboration with Dr. Mary Beth Brown in the Dept. of Physical Therapy investigates exercise effects on the pulmonary vasculature and right ventricle in pulmonary hypertension. We also collaborate closely with investigators in Physiology (Dr. Matthias Clauss) and Pediatric Pulmonary (Dr. Robert Tepper) to study lung angiogenesis and lung development, respectively.

We are part of the Pulmonary Hypertension Breakthrough Initiative (PHBI), a multi-institute program for bio-banking normal and pulmonary hypertension lung tissues and primary cell cultures. Our role is to provide genomics materials (DNA, RNA, and cDNA) to the PHBI members and complete microarray analysis. In addition, we are an enrolling center for the National Biological Sample and Data Repository for PAH. Lastly, we are participating in several multicenter clinical PH trials.

Our pulmonary vascular researchers serve as faculty on the Pulmonary and Cardiovascular T32 training grants and are members of the Indiana Center for Vascular Biology and Medicine. A monthly interdisciplinary Pulmonary Vascular Research in Progress Conference is being held on the first Thursday of each month (R3 C428, from 4:30-5:30 pm).

Researcher(s):
Dr. Mark Geraci
Dr. Tim Lahm
Dr. Bob Stearman