2013 Mentored Investigator Grant Recipient — Pradeep Chaluvally-Raghavan, PhD

Pradeep Chaluvally-Raghavan, PhD

MD Anderson Cancer Center

Role of microRNAs in the 3q26 Amplicon in Ovarian Cancer Pathophysiology and Therapy

Project Summary

Epithelial ovarian cancers are a complex group of tumors that arise from multiple different precursor tissues. High grade serous ovarian cancer, the most common and most lethal form of ovarian cancer is driven primarily by mutations in p53 and DNA copy number abnormalities (CNA). Our lab demonstrated that the consequences of 3q26.2 CNA are complex resulting in amplification and aberrant function of several tumor promoting gens such as PIK3CA, PKC?, Snon, and Mecom (EVI1 and MDS1/EVI1). However microRNAs overexpressed due to genomic amplification were not well studied. In his study Dr.Chaluvally-Raghavan focus oncogenic roles of tumor driver microRNAs amplified and overexpressed in ovarian cancers. We believe our results will bring new microRNA biomarkers and new therapeutic opportunities to target the oncogenes were previously considered undruggable.

Bio

Dr. Pradeep Chaluvally-Raghavan is an Associate Professor and the Linda and Herbert Buchsbaum, MD, Chair in Gynecologic Oncology in the Department of Obstetrics and Gynecology at the Medical College of Wisconsin. Dr. Chaluvally-Raghavan received his Liz-Tilberis Career Development award in 2016 while working as an Instructor at the MD Anderson Cancer Center. Liz-Tilberis grant facilitated his transition from Instructor to Assistant Professor in the Department of Obstetrics and Gynecology at the Medical College of Wisconsin in 2016 and subsequently to the rank of Associate Professor in 2020.

Dr. Chaluvally-Raghavan’s research focuses on mechanistic studies determining the role of protein-coding and non-coding genomic aberrations in patient tumors with a focus on RNA Binding Proteins (RBPs) and oncostatin family proteins to develop as therapeutic targets and biomarkers. His research is currently supported by the National Cancer Institute and the Department of Defense’s ovarian cancer program to continue his important work focuses on improving the quality of life of those who afflicted with ovarian cancer.

His research reported the role of dysregulation of FOXM1 and EGFR/ERBB2 signaling on the transition of the adherent form of ovarian tumor cells to become highly metastatic non-adherent cancer cells. They have also reported the mechanism that FXR1, an RNA Binding Protein promotes MYC translation by binding on its 3'UTR, promoting mRNA circularization by enforcing a circular loop between 3' and 5'UTR and also by recruiting eIF4F complex to the translation start site.

In addition to the mechanistic research, his team is developing therapeutic approaches to treat ovarian cancer. Using single-cell RNA sequencing, Dr. Chaluvally-Raghavan’s team identified that OSMR is distinctly expressed in ovarian cancer cells, thus could be targeted to treat ovarian cancer. Because no agents are currently available in the clinic to target OSMR for cancer therapy, his team has developed a monoclonal antibody that can block OSMR-signaling and patented. Dr. Chaluvally-Raghavan is now partnering with industries for future development of their antibody as an investigational drug for clinical trials.