2024 Early Career Investigator Grant Recipient — Sridevi Challa, PhD

Sridevi Challa, PhD

The University of Chicago

Targeting Ribosomal Function to Overcome Chemoresistance in Ovarian Cancer

Project Summary

High grade serous ovarian cancer (HGSOC) is the most common subtype of ovarian cancer. The standard of care for women with HGSOC is cytoreductive surgery followed by chemotherapy. Despite aggressive treatment strategies, a majority of patients with high grade HGSOC relapse. Chemotherapeutic agents target the fast-diving cancer cells; therefore, slow growing cells are not affected by chemotherapy. Accumulation of such slow growing cancer cells can potentially cause resistance. The slow growing cancer cells have high levels of stress tolerance and thus, the pathways that control stress tolerance play a crucial role in chemotherapy resistance.

We recently discovered that HGSOC cells have high levels of a specific type of protein modification that controls protein synthesis and stress responses. In the studies proposed here we will follow-up on these observations by exploring how this protein modification changes the mechanisms that control protein synthesis and stress responses in the context of chemotherapy. We will also test whether blocking this protein modification will improve responses to chemotherapy in HGSOC. Successful completion of the proposed studies will shed light on new mechanisms of chemotherapy resistance and test new therapeutic agents to increase the sensitivity of chemotherapy. These studies have a potential to improve the treatment outcomes for women with HGSOC.

Bio

Dr. Sridevi Challa is an Assistant Professor in the Department of Obstetrics and Gynecology at the University of Chicago. She earned her Ph.D. in Cancer Biology from University of South Florida where she studied the mechanisms of tyrosine kinase signaling in cancers under the mentorship of Dr. Malafa. After being awarded a Ph.D. degree in 2017, she joined the laboratory of Dr. W. Lee Kraus in UT Southwestern Medical Center as a postdoctoral researcher. During her postdoctoral fellowship she identified critical processes regulated by PARP enzymes in ovarian cancers. She demonstrated that the cytosolic NAD+ synthesis pathway controls mono-(ADP-ribosyl)ation of ribosomal proteins which maintains protein homeostasis and supports ovarian cancer cell growth. She was the recipient of an OCRA Mentored Investigator Award.

Dr. Challa joined the Department of Obstetrics and Gynecology at the University of Chicago as an Assistant Professor where she is developing a research program to address critical challenges in the ovarian cancer treatment. Research in her lab focuses on investigating the role of metabolic changes and stress responses in gynecologic cancers. Additionally, with her position as the Basic Science Lead, she is developing the Endometrial Cancer Research Program alongside physicians in the University of Chicago. Support from the OCRA Early Career Investigator Grant will be foundational for achieving her research goals.