The major focus of my lab is to understand the mechanisms utilized by invading and metastasizing tumor cells to promote expression and activity of extracellular matrix-degrading matrix metalloproteinases (MMPs). The lab currently has two projects. In our oral cancer project, we are interested in understanding how TGF-b1 signaling through Snail family of transcription factors increases MMPs and promotes invasion of oral cancer cells in 2D and 3D organotypic models of oral cancer. We have also established an orthotopic model for oral cancer wherein OSCC cells expressing GFP-tagged Snail or Slug are injected directly into the tongue to examine the role of these key proteins in promoting tumor growth and invasion in the in vivo microenvironment.

            In addition to our work in oral cancer, we have also been examining the contribution of fibrosis to pancreatic cancer progression. Fibrosis, also known as desmoplastic reaction, is a very prominent feature of almost all human pancreatic tumors, and earlier reports suggested that this desmoplasia in fact contributed to pancreatic cancer progression. We recently published that the pancreatic cancer cells adjacent to areas of fibrosis exhibit increased expression of membrane type 1-MMP (MT1-MMP). We are particularly interested in understanding how the desmoplastic reaction increases the expression of MT1-MMP in the cancer cells, thus enabling the pancreatic cancer cells to invade through a collagen-rich extracellular matrix. In addition to utilizing in vitro models to examine the cross-talk between type I collagen and MT1-MMP, we have also established a transgenic mouse model in which MT1-MMP is selectively and under regulated conditions expressed in the pancreas to examine the effect of MT1-MMP on tumor growth and on the generation of desmoplastic reaction.