Pranabananda Dutta

Assistant Professor 
Department of Internal Medicine
Charles R. Drew University

Project title: Interaction between CCL2 signaling and Poly ADP-ribosylation modulates invasiveness in triple negative breast cancer

Mentor: 
Jay Vadgama, PhD, Charles R. Drew University

Multidisciplinary expertise: Molecular Cell Biology, Cancer Biology, Genetics.

Project Description:
Triple negative breast cancer (TNBC) is an aggressive form of breast cancer with a significant health disparity. It disproportionately affects African-American women at a relatively early age and with more severity. A significant cause of mortality from TNBC is the invasive nature of the disease. However, the molecular mechanisms driving metastasis are yet to be fully understood. Chemokines related to inflammation have been linked to breast cancer in general and specifically in African-American breast cancer patients such as C-C motif chemokine ligand 2 (CCL2). CCL2 is upregulated in TNBC and controls invasiveness via the MAP kinase pathway. Moreover, CCL2 is transcriptionally regulated by Poly (ADP-ribose) polymerase 1(PARP1) and conversely controls post-translational PolyADP ribosylation (PARylation). Therefore, we hypothesize that in TNBCs, crosstalk between inflammatory chemokine pathways such as CCL2 and PARP1 activity is crucial for the cancer cells. Our study aims to show transcriptional regulators and kinases connecting the CCL2 pathway and PARP1 activity in TNBC. Furthermore, we will show that targeting inflammatory cytokine receptors (CCR2 and CCR4) and PARylation (By targeting PARP1) together will effectively treat TNBC.