During mammalian development, transcription factors and microRNAs both provide input to direct gene expression and determine lineage decisions. Some of these same pathways are recapitulated during oncogenesis and metastasis. Transcription factors controlling epithelial-mesenchymal transition are important both during development and in cancer. MicroRNAs are critical for control of gene expression and thus cell fate decisions and are often involved in temporal switches in lineage decisions. These two classes of developmental regulators have been shown to influence one another, but their mutual regulatory functions are not completely understood. I use tissue culture and mouse models to study the interplay between EMT factors and microRNAs in development and cancer, and syngeneic, xenograft, and induced pluripotent stem cell models of ovarian cancer to study disease onset and progression.
During postdoctoral studies at Harvard Medical School, I studied the mechanism of reprogramming mouse and human somatic cells to pluripotency. Surprisingly, factors involved in EMT are upregulated and play a positive role in the early stages of the induced pluripotent stem (iPS) cell generation process. The microRNA let-7 is downregulated at time points when these factors are increased, and Snail binds the promoter of several let-7 family members. Lab members will use embryonic stem cell differentiation to model gastrulation, and cell lines to model ovarian cancer, to illuminate new points of regulation in these models, and develop new strategies for inhibiting cancer cell growth.
I studied the initiation of immune responses during Ph.D. studies at Yale, where I described molecular details of the interactions between dendritic cells and naïve CD4 T cells. I am interested in using iPS cells as a source of dendritic cells for tumor vaccines in ovarian cancer.