James Marchant is a postdoctoral researcher in Alexandre Colas’s group at Sanford Burnham Prebys. In this Postdoc Portrait, he shares his work on developing a gene therapy for heart failure, why his work matters now, and his goal of developing a therapy that will one day be available in the clinic.
Q | What’s your research background?
My very first research lab experience was supposed to concretize my desire to be a marine biologist. I was a marine biology master’s student at the time, having already completed my undergraduate degree in marine biology. I was studying how fish heart cells respond to calcium at different temperatures studying calcium flux in cell populations. This interest set me on a path toward my current work.
Q | How did you first get interested in your field of research?
I became fascinated with heart cells and how they handle influx and outflow of different ions at every contraction. The coordinated molecular dance that occurs at every heartbeat is profoundly complex, and I became even more fascinated with cardiology when I started to do electrophysiology and optical mapping. Thinking about how cells are activated and interconnected to conduct action potentials to orchestrate each coordinated beat made me realize how complex cardiology is and how fragile this balancing act can be, for such an essential biological function, the being heart. This all drove me to want to learn more and to investigate how to correct the dysfunctional heart.
Q | Tell us about your favorite research project you’re working on.
My favorite research project I am working on is my cardiac reprogramming project. After a heart attack, millions of cardiomyocytes are lost and are replaced by a fibrotic scar, which greatly impairs cardiac function and ultimately leads to heart failure. Currently, there are no heart failure therapies, making this project extremely interesting! My approach uses a single therapeutic viral vector to convert fibrotic scar tissue directly into functional heart muscle. This represents a paradigm shift because previous methods required multiple viral vectors, increasing immunogenicity and reducing clinical viability. I've designed a single viral construct that delivers all necessary genetic material to reprogram non-cardiac cells back into beating cardiac muscle cells. The potential impact is enormous: offering an alternative to heart transplantation for millions of patients and eliminating the need for transplant waiting lists.
Q | What has been the most exciting part of your scientific journey so far?
The most exciting part of my scientific journey so far has been using human induced pluripotent stem cells to generate cardiomyocytes in culture. Going from stem cells to beating cardiomyocytes is extremely satisfying, especially given that they can be used to decipher the genetic determinants of disease and demonstrate the functional consequences of genetic variants on cell function, voltage generation, and calcium handling. With this model, I was able to use high-throughput biology techniques to greatly accelerate discovery in my work. Specifically, I was able to use stem cell derived cardiomyocytes from patient stem cells to discover novel genes involved in hypoplastic left heart syndrome, a congenital heart disease with very little know on its genetic determinants due to its polygenic nature. Having used a high-throughput system, coupled with artificial intelligence to discover these genes involved in disease, I can imagine that future developments in AI will further accelerate scientific discoveries in all scientific fields and I'm very optimistic about the future of science as these tools continue to develop and grow!
Q | If you could be a laboratory instrument, which one would you be and why?
I would be a patch-clamp amplifier—the instrument that measures electrical currents across cell membranes with incredible precision. Just like this instrument, I've spent my career bridging different worlds: connecting the microscopic electrical signals of individual cardiac cells to the macroscopic function of the entire heart and linking fundamental discoveries in fish hearts to clinical applications in human patients. A patch-clamp amplifier takes tiny, almost imperceptible electrical whispers from single cells and amplifies them into meaningful signals that reveal how life works at its most fundamental level. Similarly, I take small discoveries about cellular mechanisms and amplify their significance to address major clinical challenges. The patch-clamp also requires patience and precision—you must carefully approach each cell, form a perfect seal, and maintain stable conditions to get reliable recordings. This mirrors my research approach: methodical, persistent, and always striving for that perfect experimental setup that will reveal something new about how hearts work and how we can fix them when they fail.
Responses have been edited for length and clarity.
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