Professor of Medicine and Pharmacy
Norris Comprehensive Cancer Center
University of Southern California
1441 Eastlake Avenue
Los Angeles, CA 90033
Voice: 323 442 2063
1986 Searle Scholar
We are interested in the involvement of the Wnt signaling pathway in cellular proliferation and differentiation—in particular, the differential coactivator usage, and the mechanisms governing differential coactivator usage to control gene expression.
Despite their high degree of homology and similar patterns of expression, CBP and p300 play unique and distinct roles in gene regulation. Our chemogenomic studies with ICG-001, a specific CBP/beta-catenin antagonist, present clear evidence that CBP and p300 have distinct functions in regulating the transcription of Wnt/beta-catenin genes. We have developed a model, which proposes that TCF/beta-catenin/CBP-mediated transcription is critical for proliferation without differentiation (e.g. in cancer and stem cells) (Fig.1, left arm of the pathway). However, the switch of coactivators by the TCF/beta-catenin complex is the essential first step in the initiation of differentiation. The TCF/beta-catenin/p300 complex then drives the transcription of the Wnt/beta-catenin regulated genes associated with normal cellular differentiation (Fig. 1, right arm). Aberrant regulation of the balance between these two related transcriptional programs may be associated with a wide array of diseases.
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