My research program has a dual focus, first, on understanding regulatory mechanisms for proliferation of stem cells, and second on investigating novel mechanisms for how tumor cells gain diversity.
Our stem cell group focuses on understanding the molecular mechanisms underlying regulation of active cycling and quiescent stem cells in the context of intestinal development, tissue regeneration and disease. While stem cell biology is at the forefront of regenerative medicine, there lacks a clear understanding of the general mechanisms that coordinately regulate the various stem cell populations to proliferative and ultimately lineage differentiate in tissue. This lack in knowledge hampers potential to harness stem cell biology for therapeutic purposes in regeneration and disease contexts. The individual research projects in my laboratory encompass investigation of establishment of the regulatory stem cell niche during intestinal development and the dynamic remodeling of the intestinal stem cell niche during injury and disease.
Our cancer group focuses on understanding the exciting discovery that macrophages fusing with tumor cells results in generating cell fusion hybrids that retain properties of both parent cells. Our underlying hypothesis is that cell fusion can mediate acquisition of behaviors associated with M?s that contribute to metastatic cancer cell behaviors (migration, intravasation, extravasation, tissue colonization). We have evidence that these M?-tumor cell fusion hybrids more aggressively seed the liver and grow at an increased rate relative to unfused tumor cells. Further, we have shown that cell fusion underlies genetic and phenotypic diversity of the resulting progeny, suggesting that this mechanism is one way that tumors gain heterogeneity that ultimately hampers therapeutic treatment and underlies recurrent disease.