Biophysical Society Bulletin | December 2022

Biophysicist in Profile

Harpreet Singh Areas of Research Intracellular ion channels: identity and role in cardiac physiology

Institution The Ohio State University College of Medicine

At-a-Glance

Harpreet Singh , Associate Professor in the Department of Physiology and Cell Biology at The Ohio State University College of Medicine, credits his early science teachers with giving him the tools he needed to work through problems. A valuable lesson on its own, this also sparked his interest in research, which he began pursuing as an undergraduate student. The joy of discovery has kept him inspired throughout his career.

Harpreet Singh

Harpreet Singh was born in a village called Odhra, near Dasuya, Punjab, India. His father served in the Indian army, so the family moved around India in Singh’s early years. At 11 years of age, he entered a military boarding school in Chail, Shimla. It was there that he first became interested in science. “The majority of my schooling was done in the Military School, India,” he shares. “My science teachers in the school were the best ones as they encouraged us to think beyond textbooks and challenged us with problems that encouraged us to think.” Singh attended St. Joseph’s College in Bangalore, India for his undergraduate studies. “During my college years, I got an opportunity to work with my zoology professors to carry out small research projects, which earned me publications on butterflies as well as human genetics. Eventually, I was a summer intern in M. K. Mathew ’s lab at the National Centre for Biological Sciences, Bangalore, where I was introduced to ion channels. The group was working on potassium channels, and it was amazing to observe currents being recorded from Xenopus oocytes,” he explains. “That is where my interest in ion channels developed. I was fascinated by electrophysiology and the idea of currents being measured from living cells. I continued my journey into ion channel biophysics at Edin burgh University Medical School where I did my PhD under the mentorship of Drs. Richard Ashley and Michael Cousin .” As he was completing his PhD, Singh began looking for an opportunity to visualize functional ion channels at nanoscales. He undertook a postdoctoral position with Ligia Toro and En rico Stefani at the University of California, Los Angeles. “With Drs. Toro and Stefani, I established the molecular identity of a mitochondrial BK channel and visualized it with a ‘homemade’ [stimulated emission depletion] microscope,” Singh says. “We also discovered that activation of the BK channel can protect the heart from ischemia-reperfusion injury.”

“There was a time when I almost gave up my postdoctoral training, but thanks to Profs. Toro and Stefani who encour aged and supported me, I was able to give myself a second chance. My PhD mentors, Profs. Ashley and Cousin from Edin burgh, kept my morale high, and Prof. Robert Chow from [the University of Southern California] went out of his way to offer me help and guidance. I have had a strong and exceptional mentorship team that believes in my science,” he reveals. “I still remember Prof. Jianmin Cui from Washington University walking up to my poster at the Biophysical Society meeting and encouraging me to apply for faculty positions within the USA, and that was the time I really believed I had a chance at being faculty.” Singh is now an associate professor in the Department of Physiology and Cell Biology at The Ohio State University College of Medicine. “Our group focuses on newly discovered intracellular K and Cl channels in cellular organelles such as exosomes and mitochondrial membranes. We also study their role in heart failure and heart function,” he explains. “We explore the basic biophysical properties of intracellular ion channels using a combination of planar bilayers, patch clamp, near-field electrophysiology, and multi-electrode arrays. We interpret the distribution of proteins by high- and super-reso lution microscopy, and for physiology, we use optical coher ence tomography, echocardiography, and cell-based assays.” “I am extremely fascinated by ion channels and how they function. It is exciting to see how these channels maintain selectivity and open and close under different circumstances, especially in disease scenarios. I always tell my undergradu ate physiology students that ion channels are faster than you think,” says Singh. He finds the challenge of the work and the joy of discovery to be deeply rewarding aspects of his career. “Every single day

December 2022

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