Muthu Periasamy

Research Description:

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 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 to contract and relax (heartbeat). Studies show that alterations in these Ca2+ handling proteins and their function 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. These genetically altered models are characterized at the molecular, biochemical and physiological levels, using state of the art techniques, including Genomics, Proteomics and Bioinformatics. Our long-term goal is to dissect the role of several key molecules involved in Ca2+ handling, in cardiac function and disease. This research may identify potential therapeutic targets, to delay or even prevent development of Heart Failure.

Current Areas of Research:

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

Understanding SERCA pump regulation by phospholamban and Sarcolipin (a novel 31 amino acid protein) Role of luminal SR proteins in calcium storage and release (Triadin, junctin and Calsequestrin, a Ca2+ storage protein)