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We study the coordinated regulation of mammalian cell proliferation, cellular differentiation and programmed cell death in response to genotoxic and inflammatory stress. Through the investigation of Abl tyrosine kinase, we have identified a signaling network in which Abl is linked to several tumor suppressor proteins including RB, ATM, mismatch repair proteins, and the p53-family of transcription factors. Each of these proteins is regulated by genotoxic or inflammatory stress to control the cell cycle, the differentiation program and apoptosis. Interestingly, we have found that the stress-induced pro-apoptotic function of Abl and p73 is further controlled by cell adhesion through integrin-dependent mechanisms. Our current projects employ high throughput technologies, genetic screens and mouse models to further dissect the rules by which stress and cell adhesion signals are integrated to determine cell fate

Track(s):
MCB
Molecular Pathology