Muthu Periasamy, Ph.D.

Professor Chair, Department of Physiology and Cell Biology Associate Director, Davis Heart & Lung Research Institute 200 Hamilton Hall 1645 Neil Avenue Columbus  OH  43210-1218 614-292-2310 (office) 614-292-4888 (fax) periasamy.1@osu.edu

Education:
Ph.D., Biochemistry and Molecular Biology, University of Montpellier, Monpellier-Cedex, France (1976-1980)
Postdoctoral Training: Albert Einstein College of Medicine (1980-1982); Harvard Medical School, Boston (1982-1985)

Research Area:
My research is focused on cardiovascular disease, in particular understanding events that lead to heart failure. Heart failure is a progressive disease affecting the myocardium, initially causing poor pumping function and eventually resulting in death. The etiology (mechanisms) of heart failure is poorly understood and the available treatment can only prolong survival for short term. There is no real cure for heart failure and only a heart transplant can save the patient.

The heart is a muscular pump and there is a well-defined set of proteins that determine the beat-to-beat function of the heart. These proteins make up the contractile apparatus responsible for generating force (pumping) and sarcoplasmic reticulum (SR) Ca²⁺ transport proteins that regulate intracellular Ca²⁺ levels. The release and removal of calcium from the sarcoplasmic reticulum is responsible for activating the heart muscle to contract and relax (heartbeat). Studies show that changes in Ca²⁺ handling proteins both in expression and activity can be linked to cardiac dysfunction and heart failure.

Although we now know that the expression and activity of several Calcium handling proteins are altered in heart failure, we do not fully comprehend how these alterations lead to the development of heart failure. To test how altered expression or activity of the SR Ca²⁺ ATPase (SERCA) cause disease we have generated transgenic mouse models with altered SERCA protein levels. Using these genetically altered models we are studying how a decrease or increase in Ca2+ transport affect myocardial biology and function at the molecular, biochemical and physiological levels. We use a variety of techniques, including Genomics, Proteomics and calcium imaging in isolated myocytes. Our long-term goal is to study the role of Calcium homeostasis in cardiac function and disease. This research should also lead to identifying potential therapeutic targets, to delay or even prevent development of Heart Failure.

The current areas of research include:

·  The role of SR Calcium ATPase in cardiac function and disease using genetically altered mouse models

·  Understanding SERCA pump regulation by Phospholamban and Sarcolipin two small phosphoproteins

·  Role of luminal SR proteins in calcium storage and release (Triadin, junctin and Calsequestrin, a Ca²⁺ storage protein)

·  The role of Myosin Isoforms in Smooth muscle

Localization of Calsequestrin WT and Mutant CASQ to the SR. Confocal Microscopy images stained for a-Actinin (green) to mark Z-lines and CASQ2(Red) in cardiomyocytes from CASQ2D307H(TG) and WT mice. Merge shows co-localization.(Kalyanasundaram ,et al 2008)