Harpreet Singh

Research Description:

Our research is focused on organellar ion channels and their physiological roles. Cellular organelles have a wide range of membrane potential which arises from ion channels and transporters. The major challenge is the lack of molecular identity and associated physiological roles of organellar ion channels. Our studies are focused on establishing the molecular identity of organellar ion channels. In our ongoing quest to identify new ions channels, we have so far established the molecular identity of three mitochondrial and one exosomal ion channel. Our next steps involve understanding the role of organellar channels in organelle physiology. It could range from packaging cargo to maintaining structural integrity to energy production. Currently, we are investing the role of organellar channels in cardiac function and cardioprotection from ischemic injuries. These are being tested in animal and HiPSC derived cardiomyocytes. Techniques in the laboratory range from single-channel electrophysiology (Bilayer, patch-clamp, and near field electrophysiology) to super-resolution microscopy, animal physiology, and large-scale electrophysiology screening (multi-electrode arrays and SyncroPatch).

Current research projects are:

1. Molecular identity and role of intracellular chloride channels in cardiac physiology.
We are investigating the roles of CLICs in heart failure and diabetic cardiomyopathy. We have established the molecular identity of the first inner mitochondrial membrane chloride channels as well as the first mitochondrial associated membrane chloride channel.

2. Role of intracellular potassium channels (iBK) in cardiac hypertrophy.
We have discovered the largest conductance K channel is exclusively present in cardiomyocyte mitochondria (but in the plasma membrane in all other cells). We are not determining its role in protecting the heart from ischemic injury. We are using mice (neonates and adults) and human baby hearts models for our studies.

3. Exosomal ion channels.
We have recorded exosomal ion channels by state-of-the-art near-field electrophysiology. We are now establishing the role of exosomal ion channels in exosome integrity. Exosomes are promising vehicles for drug/ cargo delivery in several pathological conditions including but not limited to cancer, and heart and muscle diseases. We have introduced ion channels as key players in regulating exosome physiology.