Sunil Sudarshan, M.D., a professor in the Department of Urology, has been recognized as the latest winner of the Heersink School of Medicine’s Featured Discovery. This accolade honors and celebrates the significant research contributions made by Heersink’s faculty members.

The study, “L-2-hydroxyglutarate remodeling of the epigenome and epitranscriptome creates a metabolic vulnerability in kidney cancer models,” was published in the Journal of Clinical Investigation.

The research was concentrated on kidney cancer, one of the 10 most common cancers in the United States. It was discovered that a specific metabolite (a small molecule) is frequently elevated in kidney cancer. Elevated levels of this metabolite in cancer cells lead to metabolic remodeling, creating a metabolic vulnerability that could be targeted for cancer treatment.

The Heersink communications team met with Sudarshan to gather insights and promote awareness about the study and the Heersink School of Medicine.

Q. What was your most unexpected finding?

We first discovered that the molecule L-2-hydroxyglutarate (L-2HG) is commonly increased in renal cancer. We had shown that L-2HG promotes the growth of kidney cancer cells. However, we were quite surprised to find that the metabolite also suppresses the expression of enzymes that mediate synthesis of the amino acid serine. As serine is very important for cancer cells, our findings were counterintuitive. Nevertheless, they led us to uncover a metabolic liability that could be exploited to treat kidney cancer.   

Q. How do you feel your research will impact the science community?

It’s pretty well known that cancer cells often have nutrient requirements that outweigh their biosynthetic capacity. Hence, they must rely on exogenous sources for certain nutrients. However, the mechanisms that confer this dependence are poorly understood. Furthermore, these demands and mechanisms are heavily context dependent (i.e. tumor specific). Our data provide a mechanistic basis by which metabolic liabilities are created specifically in renal cancer cells.   

Q. When did you know you had an important discovery? 

We saw a clear signal from our gene expression studies at the start of this project.The real struggle was making sense of it all. L-2HG can have a myriad of effects on a cancer cell. Deconvoluting how L-2HG created this liability took us some time, but it’s also led us into new research directions. 

Q. How has being at UAB and living in Birmingham affected your research? 

UAB provided me with the resources and infrastructure to carry out our science. Birmingham has been a great place for my family and is an easy place to live. As such, it’s allowed me to maximize time for the lab while at the same time leaving enough time to relax, take care of myself, and enjoy life. An integral part of it all has been the people at UAB. I have been very fortunate to have great mentors, colleagues, and collaborators as well as the support of my department.

Q. What made you come to UAB? 

I came to UAB at a critical time in my career. I was only five years out of training. While there are many opportunities when you first start out, the first big hurdle is getting your first independent grant. This institution really provided the support to make that first big jump.