Sridevi Challa, PhD

Every year, more than 20,000 women in the United States are diagnosed with ovarian cancer. Most respond to treatment at first, but nearly all will relapse, at which point there are very few treatment options. Hence, new treatments for relapsed ovarian cancer are urgently needed. Part of what makes this cancer so deadly is that tumors become resistant to drugs. Tumors also spread to fatty tissue in the abdomen, where fat cells feed the cancer cells and protect them from treatment.Our research focuses on a protein called NMNAT2. This protein helps cancer cells make NAD+, a molecule they need to grow, survive, and resist treatments. We found that ovarian cancers with high NMNAT2 are more aggressive and harder to treat. NMNAT2 also helps cancer cells use fat cells to spread. Crucially, NMNAT2 is highly expressed in ovarian cancer but rarely found in normal tissues. This makes it a safe and precise drug target.In the proposed studies, we will test how NMNAT2 drives drug resistance and tumor spreading. We will also test whether blocking NMNAT2 makes tumors easier to treat by changing their immune environment. By understanding how NMNAT2 is controlled, we aim to develop new treatments for treatment-resistant ovarian cancer and improve outcomes for patients with this deadly disease.