2016 Mentored Investigator Grant Recipient — Abir Mukherjee, PhD

Project Summary

Ovarian cancer (OvCa) patients are often diagnosed with advanced disease due to lack of early detection
methods. Once detected patients undertake surgery to remove tumor tissue and subsequently undergo
chemotherapy. However majority of patients come back with a recurrent disease resistant to available
treatment. Since 1999 when liposomal doxorubicin (Doxil®) was introduced, the survival of patients with
the disease has only improved minimally. In addition, emergence of chemoresistant tumors has severely
limited effective therapy, necessitating further research to identify and target new molecules.
OvCa arising from either the surface of the ovary or the distal end (fimbriae) of the fallopian tube has a
unique mode of spread. Cancer cells are shed from the primary tumor and are freely spread by the
peritoneal fluid homing primarily to the omentum (80%), a fat pad of about 20x15x2 cm in size covering
the bowl. Metastatic ovarian cancer cells at the omentum are exposed to a lipid rich environment and
the cells respond by enhancing uptake and intracellular accumulation of lipids. The omentum largely
composed of adipocytes (fat cells) provides a unique environment for the metastatic progression of
OvCa cells. Adipocytes and adipocyte-secreted factors have been implicated in the proliferation of
several types of cancer, including breast, colon, and prostate. We previously reported how adipocytes
promote OvCa metastasis, invasion, and proliferation.

Our preliminary data in this proposal suggests that certain factors secreted by adipocytes increase
amount of a protein (Hif-1a) known to be present in cells under reduced oxygen concentration. It is
possible that there exist a new pathway by which cancer cells can increase this protein to help them
cope with unfavorable condition. Increased presence of hif-1a can facilitate cancer cells to change their
nutrient source and opt for ones that are readily available and help cancer cells to multiply. Through this
proposal we plan to identify the factor/s that increases this protein amount in cancer cells. Then we will
try to understand how cancer cells benefit from this protein and ultimately we will use mouse
experiments to understand how loss or increased amount of Hif-1a affects tumor formation. Hence this
proposal has the potential to identify a target for therapy against OvCa.

Bio

Abir Mukherjee PhD is a postdoctoral scholar in the laboratory of Dr. Ernst Lengyel at the University of Chicago. Dr. Mukherjee received his bachelor’s degree in Microbiology and Biochemistry from the University of Mumbai (Mumbai, India), his master’s degree in Molecular and Genetic Medicine from The University of Sheffield (Sheffield, England) and his Ph.D. from the Virginia Commonwealth University (Virginia, USA). His doctoral research focused on bioactive lipid mediated signal transductions via G-protein coupled receptors in ovarian cancer. His current research focuses on the bidirectional signaling that occurs between stromal and cancer cells in the metastatic ovarian cancer microenvironment. Dr. Mukherjee’s goal is to understand the altered metabolism in cancer cells induced by stromal cells, and identify suitable therapeutic targets.