Biography
Andrew R. Marks graduated from Amherst College in 1976 and from Harvard Medical School in 1980. Following an internship and two years of residency training in internal medicine at the Massachusetts General Hospital he completed a postdoctoral fellowship in the Department of Molecular Biology with Howard Goodman at MGH. Dr. Marks then completed two years of clinical training in cardiology and is board certified in Cardiovascular Diseases. In 1987 he joined the faculty of the Cardiology Division at the Brigham and Women’s Hospital in Boston and at Children’s Hospital where he worked in the laboratory of Bernardo Nadal-Ginard until 1990 when he became an Assistant Professor of Molecular Biology and of Medicine at the Mount Sinai School of Medicine in New York. In 1995 he was named the Fishberg Associate Professor of Medicine (Cardiology) at Mt. Sinai and was Director of the Cardiology Training Program from 1993-1997. In 1997 he moved to the College of Physicians & Surgeons of Columbia University where he is the Clyde and Helen Wu Professor of Molecular Cardiology, Professor of Pharmacology and Director of the Center for Molecular Cardiology. Dr. Marks’ awards and honors include the Syntex Scholars Award, American Heart Association Established Investigatorship Award, membership in the American Society of Clinical Investigation (ASCI), and the Association of American Physicians. Dr. Marks served as an elected member of the ASCI national council (1997-2000). Dr. Marks’ research has focused on the molecular regulation of intracellular calcium release channels.
Abstract
Novel Approaches to Treating Heart Disease
Heart failure is the leading cause of death in the developed world. When heart damage occurs the amount of blood pumped by the heart to the organs of the body (including the brain, kidneys, liver etc.) is diminished. In response to the decreased pumping action of the damaged heart the brain sends out signals to make the heart muscle pump more strongly. These signals include the release of adrenaline into the blood stream. In the normal heart adrenaline makes the heart beat more strongly, but in damaged hearts it fails to do so. Dr. Mark’s work demonstrated that one of the targets of the adrenaline is a calcium channel inside heart muscle cells called the ryanodine receptor. When calcium levels increase heart muscle contracts and pumps blood. The ryanodine receptor is the door that lets calcium out of storage compartments and into the rest of the heart muscle cell where it can trigger muscle contraction. When the brain detects a weakened heart muscle contraction it sends out the message (adrenaline) to tell the heart to beat more strongly. Adrenaline activates the calcium channels to release more calcium resulting in a stronger contraction. In failing hearts adrenaline results in overstimulation of the ryanodine receptor, resulting in loss of calcium from the heart muscle, and an even weaker heart. Thus drugs, such as beta adrenergic blockers (beta blockers) which block the overstimulation of the calcium channel in the heart muscle cell should prevent this calcium leak. Dr. Mark’s work predicts that by blocking the overstimulation of the calcium channel with beta blockers, heart muscle contraction should improve.
The proposed studies will:
- Identify molecules (eg. proteins) that regulate the calcium channel and could become new targets for drug therapy aimed directly at controlling the release of calcium; and
- Identify drugs that can act directly on the calcium channel to stabilize it’s function so that it doesn’t become leaky in response to the over stimulation by adrenaline.
These approaches should allow for more potent therapy with less toxic side effects.