The current program of the Singh laboratory is aimed at deciphering molecular identity of mitochondrial ion channels, establish their localization and biophysical properties, and study their role in mitochondrial as well as cell physiology. Mitochondria is a key player in pathological and physiological conditions ranging from heart failure, cancer to normal functioning of organs. The lab’s immediate interest is on studying mitochondrial ion channels and their relation to heart function and heart failure. The lab’s research program is focused on following projects:
Molecular identity and Physiological role of mitochondrial potassium channels
The Singh lab has established that the large conductance calcium and voltage activated potassium channel (BKCa) is exclusively present in mitochondria of adult cardiomyoyctes. Activating BKCa protects the heart from ischemia-reperfusion (IR) injury and blocking BKCa increases myocardial infarction. The lab’s program is focused on understanding the mechanism of cardioprotection from IR injury via activating BKCa.
Mitochondrial Chloride Channels
Mitochondrial membranes are known to possess several ion channels which play a key role in maintaining and regulating ionic homeostasis. The singh lab has discovered that the Chloride Intracellular Channel 5 (CLIC5) localizes to the inner membrane of cardiac mitochondria whereas CLIC4 is present in both membranes. The lab is now focused on understanding the role of CLIC4 and CLIC5 in cardiac mitochondrial physiology. It is also studying their roles in cardiopulmonary diseases and molecular mechanisms involving CLICs.
The Singh lab’s long term goal is [to] determine molecular mechanisms involved in cardiac physiology and pathophysiology which could result in identifying new therapeutic targets for cardiovascular diseases.