Grants - V Scholar Grants - Ohio - 2020

Abhishek Chakraborty, PhD

Kidney cancer is among the ten most common forms of human cancer. While manageable in early stages, advanced kidney cancer remains incurable. Therefore, new drugs to treat this disease are urgently required. 

Kidney cancers emerge when normal kidney cells acquire changes in their genetic program. DNA, ouprimary genetic source-code, is like a thread that is compactly wrapped into a complex spool called “chromatin”. This wrapping protects DNA from environmental adversity and also allows precise control to switch genes on/offwhen desired. Importantly, many of the kidney cancer-causing genetic changes promote improper “chromatin” spooling, which possibly drives cancer growth by switching on the function of key tumor-promoting (onco)genes. Identifying and shutting off these misfiring oncogenes could thus block tumor growth, and be a means of therapy.   

Our laboratory has begun comprehensively probing this idea. Using cutting-edge technology, wfirst identified numerous genes that were associated with improper “chromatin” spooling and thus were erroneously switched on in cancerous kidney cellsAmong these genesour follow-up studies shortlisted ten candidate oncogenes that promoted tumor growth in mouse models. Many of these gene products rewire the cancer cell’s metabolismHere, we address which of these metabolic functions are indispensable for kidney cancer and how these changes fuel cancer growth. Cancer cells are perpetually hungry for nutrients to support their uncontrollable growth; therefore, starving kidney cancer cells of essential nutrients can be exploited for therapy. Together, our studies lay the foundations to establish such metabolic genes as clinically useful targets to treat kidney cancer.