SCHOOL OF MEDICINE

Department of Medicine

Pulmonary, Critical Care, Sleep & Occupational Medicine

Welcome to the Lahm Lab

The overall goal of the Lahm lab is to find novel treatments for pulmonary hypertension (PH), a sexually dimorphic and progressive cardiopulmonary disease characterized by excessive pulmonary artery (PA) vasoconstriction and remodeling, ultimately leading to right ventricular (RV) failure and death. One of our main projects is to identify the mechanisms by which sex hormones and their receptors affect pulmonary vascular remodeling and RV function in PH. In particular, we are investigating how global and local hypoxia affect estrogen receptor expression and function in the pulmonary vasculature and right ventricle. We have now expanded these studies in order to study the role of testosterone and the androgen receptor in RV failure. Another major project centers around the role of autophagy in the development of right ventricular failure.

 

We perform our research in in vivo rodent models of adaptive and maladaptive right ventricular remodeling (hypoxia-induced pulmonary hypertension and sugen/hypoxia-induced pulmonary hypertension), in an ex vivo model of isolated rat pulmonary artery rings, and in vitro in primary pulmonary artery endothelial cells, H9c2 cardiomyoblasts and isolated primary cardiomyocytes (isolated via a perfused heart model). The Lahm lab has a unique set up for the comprehensive assessment of physiological endpoints such as hemodynamics (in collaboration with Dr. Robert Presson, IU Dept. of Anesthesia), pressure-volume loops, echocardiography, and exercise capacity (with Dr. Mary Beth Brown, IU Dept. of Physical Therapy). Assessment of morphological and biochemical endpoints centering around cell survival, autophagy and mitochondrial bioenergetics is performed in collaboration with Dr. Irina Petrache (National Jewish Health). Resources in the Lahm lab include two in vivo hypoxia chambers, an in vitro hypoxia workstation, advanced hemodynamic monitoring equipment, a pulmonary artery ring bath, a Flexivent rodent pulmonary function testing machine, and a chemidoc. The Lahm lab takes particular pride in the mentoring of several fellows, residents, as well as Life Health Sciences Initiative (LHSI) students, Bridges to Baccalaureate students, and Project SEED students. We are funded by the Department of Veterans Affairs and the NIH, as well as through intramural grants.

 

Active basic science projects in the Lahm lab are as follows:

  • Protective estrogen receptor signaling in hypoxia-induced pulmonary hypertension and severe right ventricular failure (Dr. Andrea Frump, postdoctoral fellow)

  • Testosterone effects in right ventricular failure (Dr. Jordan Whitson, postdoctoral fellow)

  • Role of autophagy in right ventricular failure (Collaboration with Dr. Michael Boulton, IU Dept. of Ophthalmology)

  • Sex differences in the right ventricular autophagy response to exercise in experimental pulmonary hypertension (Collaboration with Dr. Mary Beth Brown, IU Dept. of Physical Therapy)

  • Estrogen effects on RV-PA coupling in RV failure (Collaboration with Dr. Naomi Chesler, Univ of Wisconsin)

  • Sex steroid receptor expression in human RV failure (Collaboration with Drs. Sebastien Bonnet and Steeve Provencher; Université Laval, Quebec, CA)

  • Effects of perinatal hyperoxia and arrested lung development on development of pulmonary hypertension later in life (in collaboration with Dr. Kara Goss, Univ of Wisconsin, Dr. Shawn Ahlfeld, Cincinnati Children’s Hospital, and Dr. Robert Tepper, IU Dept. of Pediatrics)

  • Effects of chronic hypoxia exposure on lung development (Collaboration with Dr. Robert Tepper, IU Dept. of Pediatrics)

  • Role of EMAP II in pulmonary hypertension development (Collaboration with Dr. Matthias Clauss, Indiana Center for Vascular Biology and Medicine)

 

The Lahm lab is actively involved with the following clinical investigations:

  • Clinical Investigation of a Daily Walking Program plus L-Arginine Supplementation for the Treatment of Pulmonary Arterial Hypertension (role: co-investigator; PI: Mary Beth Brown, PhD)

  • Inhaled nitric oxide to treat severe PE (iNOPE; role: co-investigator; PI: Jeff Kline, MD; IU Dept. of Emergency Medicine)

  • Combined pulmonary fibrosis and emphysema in veterans (role: PI; collaboration with Dr. Karina Serban; National Jewish Health)

  • Analyzing the Veterans Affairs-Clinical Assessment Reporting and Tracking (VA-CART) database to define national trends in prevalence, clinical profile, and consequences of pulmonary vascular disease on outcome in a large patient population (role: study committee member; PIs: Bradley A. Maron, MD (Harvard University) and Gaurav Chaudhary, MD (Brown University))

  • National Biological Sample and Data Repository for PAH (role: local PI; PI: Dr. William Nichols, Cincinnati Children’s Hospital)

 

Current lab members:

  • Tim Lahm, MD (PI)

  • Andrea Frump, PhD (Postdoctoral fellow)

  • Jordan Whitson, MD (Postdoctoral fellow)

  • Marjorie Albrecht (Research Associate)

  • Bakhtiyor Yakubov, PhD (Research Associate)

  • Jordan Baum (LHSI student)

 

Lahm lab alumni and their destiny:

  • Dr. Brent Toney - Private Practice; St. Vincent Hospital, Indianapolis, IN

  • Dr. Mona Selej - Pulmonary Hypertension Fellowship; Stanford University; now at Actelion Pharmaceuticals, San Francisco, CA

  • Dr. Kara Goss - Assistant Professor of Medicine, Pulmonary/Critical Care Division; University of Wisconsin, Madison, WI

  • Dr. Anthony Cucci - Private Practice; Akron, OH

 

Helpful links:

 

Contact and mailing address:

Lahm lab

980 W. Walnut Street, room C407

Indianapolis, IN 46202

Phone: 317.278.5397

Fax: 317.278.7030