The broad goal of my research program is to understand how mutations of transcriptional regulators may set up patterns of aberrant gene expression that yield cancer. This requires a detailed understanding of the normal function of these transcription factors. Such information includes an understanding of the role of these factors in cell growth, differentiation and developmental, the normal DNA binding and transcriptional activity of these proteins, identification of the critical protein partners of the factors and elucidation of the downstream targets of these genes. The mutations that occur in cancer are tragic experiments of nature that may alter critical amino acid residues for the function of the proteins. By modeling the function of both the normal and mutated forms of these factors we hope to better understand the molecular basis of cancer and potentially identify new therapeutic targets and pathways in this disease.



Reciprocal signaling between the ureteric bud (UB -Green) and metanephric mesenchyme (Red) guides kidney development. Factors from the UB, including LIF and FGFs induce condensation of the mesenchyme and may induce the expression of factors like WT1 and Pax2 critical for epithelial differentiation. WT1 may induce the expression of growth factors like amphiregulin, Wnt4 and GDNF which stimulate the UB and mesenchyme. At the same time WT may induce the expression of sprouty a counter-regulatory factor THAT limits the effects of growth factor signaling on the condensing mesenchme.