Alex Sternisha is an M.D./Ph.D. student in the Medical Scientist Training Program (MSTP) at UT Southwestern. In the McBrayer lab, he studies how small molecules that are produced and consumed by living cells can control the fate of individual cells by shaping genomic DNA structure.
What are you researching?
I am studying how cells regulate the abundance of a small molecule metabolite, called alpha-ketoglutarate (aKG), that controls DNA organization and cell identity. aKG is best known for its role in the tricarboxylic acid (TCA) cycle in the mitochondria but is also used by enzymes in the nucleus that chemically modify DNA. Importantly, relatively small changes in aKG levels can have a dramatic impact on DNA structure, which in turn affects gene expression. In many cellular contexts, alpha-ketoglutarate metabolism has been linked with regulation of gene expression programs that dictate cell fate decisions and influence differentiation.
Although the ability of aKG to control DNA structure is well established, the network in cells that controls this molecule is not well understood, in part because over 100 enzymes either produce or consume this metabolite. To tackle this problem, I have been working on developing a new technology to directly assess changes in aKG levels in living cells. Combining this technology with focused genetic screens will allow us to identify critical nodes in the metabolic network that controls aKG abundance.
After optimizing this technology, I plan to apply it to study aKG metabolism in a variety of physiological and pathophysiological conditions, including cancer. Our work will hopefully reveal important ways that metabolism shapes the behavior of tumor cells and highlight new strategies for cancer therapy.
How did you end up at CRI?
When I was interviewing for M.D./Ph.D. programs, I was impressed by the quality of science that was being undertaken at the CRI. During my first two years in medical school, the MSTP hosted weekly works-in-progress talks from faculty members who shared their research. Dr. Sam McBrayer gave an impressive talk highlighting the research he did during his postdoctoral fellowship, and I requested a meeting with him to discuss projects in his newly formed laboratory. I ended up doing a rotation in the lab and really enjoyed my time working with him and the CRI community. A common theme within the institute is the push to make impactful discoveries and the CRI provides many resources to do so, including a collaborative and supportive environment.
How did you become interested in your field?
I’ve been drawn to a career as a physician-scientist primarily by my desire to make impactful research discoveries to improve our understanding and treatment of cancers. Nearly everyone is affected by cancer in their lifetime. The burden of cancer is significant, both in terms of morbidity and mortality. Historically, cancer treatments have been relatively nonspecific and come with unwanted side effects. In recent years, the scientific community has made advances in improving targeted therapies, and my hope is to contribute to that throughout my career.
What do you like to do when you’re not in the lab?
Dallas has a great food scene, and I’ve enjoyed going out and exploring the wide array of quality restaurants in the area. Besides that, I like playing sports and trying to stay active. I also follow the NFL closely, with my favorite team being the Buffalo Bills.
What is the hardest part of grad school?
Like many of my colleagues would say, the hardest part of grad school is the uncertainty. The contrast with medical school is especially stark, as the medical school curriculum is extremely regimented. Nothing in science is guaranteed to work out, but I’m fortunate to be in a great environment where everyone is willing to lend a helping hand.
