December 09, 2020

PRDM16 suppresses HIF-targeted gene expression in kidney cancer

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sudarshsSunil Sudarshan, M.D., professor in the Department of Urology, is the latest winner of the School of Medicine’s Featured Discovery. This initiative celebrates important research from School of Medicine faculty members.

Sudarshan’s study, “PRDM16 suppresses HIF-targeted gene expression in kidney cancer,” published in Journal of Experimental Medicine, researched extensive epigenetic gene silencing in renal cancer, which can impact renal tumor growth.

Sudarshan and his team examined the biologic consequences resulting from loss of a transcription factor, referred to as PRDM16, in kidney cancer. Lead author, Anirban Kundu, Ph.D., is a postdoctoral fellow in the Sudarshan lab. This factor has a prominent role in adipocyte physiology, but it is also highly expressed in the kidney. The team found that PRDM16 is lost in kidney cancer, and loss of this factor led to enhanced expression of the signaling molecule semaphorin 5B (SEMA5B). In turn, SEMA5B is what drives renal tumor growth.

This work will contribute to effective treatments and potentially better outcomes for patients with renal cancer. Read the full publication here.

The School of Medicine communications staff sat down with Dr. Sudarshan to gain insights about the research of this study, UAB, and the science community.

Q: What compelled you to pursue this research?

We focused on PRDM16 because it is markedly suppressed in renal cancer based on a bioinformatic analysis. At the same time, the factor is highly expressed in normal kidney. Yet, the role of this factor in renal physiology and pathology was completely unknown. We, therefore, thought this was an opportunity to pursue a novel line of investigation.

Q: What was your most unexpected finding?

As a transcription factor, PRDM16 has functions that can both turn on and off gene expression. We were initially focused on its activating activities based on the literature. However, our studies demonstrate that its suppressive properties dominate the transcriptional landscape. Importantly, it was this repressive property that is responsible for its effects on renal tumor growth.

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

We think that the studies open up new avenues to go after. There are definitely other genes that PRDM16 silences that we are interested in. Additionally, we are very interested in SEMA5B as we have identified a novel mechanism by which this factor signals in cancer cells.

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

I am fortunate to be in a very supportive department, chaired by Dean Assimos, along with exceptional colleagues who believe in the research mission. I have also found UAB to be a highly collaborative environment. The results of our study were highly dependent on these collaborations from several departments across campus. Most importantly, I get to work with a dedicated team that really drives these projects forward. The best part of my day is interacting with these individuals as we try to make progress in the lab.

Q: What made you come to UAB?

A job! It was a great opportunity for me and well as my wife, Margaret Boozer (in the Department of OB/GYN at UAB). We have really come to love Birmingham and being part of the UAB community. When you move around so much during various phases of training and academia, it’s been great to come to a place that feels like home.

Read the publication here.