Dharmalingam Subramaniam, Ph.D.
Research Assistant Professor
My laboratory is focused on chemoprevention by natural products and their analogs which inhibit the growth of colon and pancreatic cancers.
a) Chemoprevention is to determine the signaling mechanisms by natural products or dietary phytochemicals and their analogs which inhibit the growth of colon and pancreatic cancer cells. We have identified a natural compound from the Ayurvedic plant Aegle marmelos called HDNC (Marmelin) that inhibits colon cancer growth by affecting the NF-κB pathway. In addition, we worked on curcumin and its derivatives, EF24 and DiFiD. These derivatives are more potent than the parent compound. Moreover, we showed that EF24 inhibited colon cancer by suppressing the EGFR signaling pathway. We also demonstrated that DiFiD and another natural compound Quinomycin A inhibit pancreatic cancer growth by suppressing the Notch signaling pathway.
b) There is compelling evidence to suggest that tumor microenvironment plays a critical role in pancreatic cancer progression and metastasis. Cancer progression is dependent on a stroma that contains blood vessels, inflammatory cells, and fibroblasts. Within the stroma, tumor associated fibroblasts (TAF) are the primary cell types which play an important role in tumor progression. TAFs secrete several factors that promote proliferation, invasion, and metastasis of cancer cells and modulate drug resistance. We are targeting signaling molecules involved in the cross-talk between epithelial cells and fibroblasts to induce tumor progression and metastasis. We are now focusing on cancer stem cells and associated signaling pathways and the role of the tumor microenvironment especially TAFs in pancreatic cancers.