Dorothy M. Davis Heart and Lung Research Institute 

Jay Zweier, MD, Director

The Ohio State University’s Dorothy M. Davis Heart and Lung Research Institute (OSU DHLRI) is one of the nation’s few free-standing facilities devoted entirely to the research of diseases affecting the heart, lungs and blood vessels. Its mission is to develop novel strategies to prevent and cure heart and lung diseases. The Institute is an internationally recognized center of excellence for medical research that leads to findings with broadbased applications to other diseases and conditions.

Ongoing Research Programs

Four major thematic areas:

  • Myocardial ischemia and metabolism
  • Myocyte biology and disease
  • Inflammation, fibrosis and immune function
  • Regenerative medicine

Sub-areas of specialized focus:

  • Cardiovascular and molecular imaging
  • Cardiovascular genomics and pharmacogenomics
  • Myocardial salvage and regeneration post myocardial infarction
  • Molecular therapies and devices for the treatment of heart failure
  • Fibrosis, remodeling and lung injury
  • Innate immune system function
  • Mitochondria biology and critical care disease
  • Control of lung inflammation to prevent lung fibrosis
  • Environmental and smoking-induced heart and lung disease
  • Tissue engineering and stem cell biology
  • Nitric oxide biology and signaling
  • Redox biology and free-radical research
  • Molecular and cellular therapies of tissue repair and wound healing

Research Accomplishments of 2006

  • Demonstrated that sustained reverse left ventricular structural remodeling, at one year, can be achieved with cardiac resynchronization, and that this efficacy is a function of the etiology of heart failure.
  • Demonstrated that monocyte chemoattractant protein-1 induces a novel transcription factor that causes cardiac myocyte apoptosis and ventricular dysfunction.
  • Identified an aspirin derivative that donates nitric oxide, is highly effective in myocardial protection and shows potential to enhance cancer therapy.
  • Determined the effects of platelet antigen polymorphism on platelet inhibition by aspirin, clopidogrel or their combination.
  • Demonstrated that microRNA-155 regulates human angiotensin II type 1 receptor expression.
  • First identified that abnormal interactions of calsequestrin with the ryanodine receptor calcium release channel are linked to exercise-induced sudden cardiac death.
  • Demonstrated that mitochondrial iPLA2 activity modulates apoptosis through the release of cytochrome c from mitochondria and influences the permeability transition.
  • Demonstrated that proteasome inhibition downregulates endothelial nitric oxide synthase phosphorylation and function.
  • Characterized the mechanism by which nitric oxide and nitrosothiol generation occurs from organic nitrates.
  • Performed the first transcriptome analysis of the ischemia-reperfused remodeling myocardium, which identified the temporal changes in inflammation and extracellular matrix.
  • Collaboratively recruited key assistant professors in the Department of Internal Medicine’s Division of Cardiovascular Medicine and in the School of Public Health.
  • Collaboratively recruited key professors in the Department of Internal Medicine’s Division of Cardiovascular Medicine and in the Department of Surgery’s Division of Cardiothoracic Surgery
  • Established an Intramural Thematic Grants Program to encourage and support DHLRI investigators in developing programs and careers in the four major thematic research areas. In autumn 2006, the program funded 12 investigators for a total of $831,855.
  • Identified three genetic mutations that predispose young individuals to sudden cardiac death.
  • Received two National Institutes of Health programmatic grants (PPGs) in ischemic heart disease and myocardial protection in partnership with other institutions.
  • Received approximately $4 million from the National Institutes of Health and the National Institute of Biomedical Imaging and Bioengineering for establishing the nation’s first program for proton electron hyperpolarization imaging.
  • Received funding for the first redox proteomics grant.
  • Created the Ohio State University Vascular Research and Imaging Center and recruited a director.
  • Continued growth of the Cardiac MRI and CT program.
  • Created the Clinical and Research Center for Echocardiography and recruited a director.
  • The Comprehensive Wound Center, established by DHLRI investigators, became a University-recognized center. 

Research Accomplishments of 2005

  • Identification of a molecular defect in cardiac cells that is a fundamental cause of heart failure. It was shown that, in heart failure, ryanodine receptors become leaky, leading to calcium imbalances.
  • Demonstration that exercise training prevents ventricular fibrillation induced by myocardial ischemia. Endurance exercise training increased cardiac parasympathetic regulation.
  • A recently discovered protein, sarcolipin, was shown to be an important regulator of calcium transport in the heart.
  • Tocotrienol was identified as a potent neuroprotective form of natural vitamin E against stroke.
  • Oxygen-sensing nanoparticulates were developed to label and track stem cells.
  • New molecular imaging agents were developed and shown to detect cell death and apoptosis in atherosclerotic coronary lesions.
  • The clinical value of cardiac resynchronization in the treatment of heart failure was characterized, leading to improved treatment of heart failure.
  • A molecular pathway of the activation of the antianginal drug nitroglycerin was elucidated.
  • Endogenous inhibitors of the critical vasodilating enzyme nitric oxide synthase were identified and shown in cardiovascular disease to rise to levels that induce vascular dysfunction.
  • A technique was developed for in vivo measurement of oxygen levels in the heart, and scientists demonstrated that marked hyperoxygenation occurs upon postischemic reperfusion.
  • The Institute established four thematic programs of central importance linking all OSU DHLRI investigators. These programs include: myocyte biology and disease; ischemia and metabolism; regenerative medicine; inflammation, fibrosis and immune function. Each has a translational research focus linking basic science and clinical studies.
  • The Institute created the OSU Comprehensive Wound Center.
  • The Institute created clinical cardiac MR and CT facilities in partnership with the Heart Center and the OSU Richard M. Ross Heart Hospital, and recruited a leader for cardiac MR and CT research.
  • Collaborative recruitments of key faculty in Cardiovascular Medicine and Vascular Surgery were realized.
  • A high-resolution small-animal MRI system was procured and installed as part of DHLRI Core Laboratories.
  • The Institute received a National Institutes of Health-National Center for Research Resources shared instrumentation grant to help establish a biomedical atomic force microscopy core facility.

OSU Dorothy M. Davis Heart and Lung Research Institute
473 W. 12th Avenue
Columbus, OH 43210
(614) 247-7766

http://medicalcenter.osu.edu/research/centers/dhli/index.cfm