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our Research

Our group is broadly interested in how genetic abnormalities in breast cancer and related malignancies influence tumor biology, and how that biology can, in turn, be exploited to therapeutic advantage.

We address these questions through basic research studies of key cancer drivers including DNA repair defects through BRCA1/2 and related pathways, and transcriptional reprogramming through the p53 gene family. Supporting and complementing these studies are leading-edge analyses of patient-derived precancerous and cancerous tissues. Recent innovative tissue-based studies have led to our discovery of novel cancer drivers, and have provided a unique window on early cancer pathogenesis, intratumoral heterogeneity and tumor progression. Our discoveries in the basic laboratory and through human tumor analysis are being applied in ongoing clinical trials that seek to identify predictive markers of response to specific therapeutics for breast and other cancers. Our ability to work at the interface of basic tumor biology and therapeutic application is strongly supported by our network of collaborators and by the research and clinical infrastructure of the Mass General Cancer Center.

Major Research Topics

The p53 family network in cancer biology and therapy

The p53 tumor suppressor is inactivated in more than 50% of sporadic human cancers, and patients carrying heterozygous germline p53 mutations show striking tumor predisposition. As a transcription factor and key nodal point for integrating cellular responses to DNA damage, p53 regulates genes involved in diverse cellular processes including cell cycle progression, apoptosis and angiogenesis. Through analysis of two p53-related genes, p63 and p73, we and others have defined a functional network through which these factors interact in human tumorigenesis. We have further defined a tissue-specific role for p63 as the enforcer of an epigenetically-controlled stem/progenitor state. Tumor-selective deregulation of p63 and its associated chromatin remodeling factors reprograms the transcriptome and thereby promotes proliferation, inhibits differentiation, and contributes to immune evasion. These findings are likely to explain the observation that p63 is over-expressed in a broad variety of epithelial tumors, particularly squamous cell and breast carcinomas. Collectively, this work serves as a paradigm for analysis of transcriptional reprogramming in cancer, while potentially providing new therapeutic possibilities for multiple treatment-refractory malignancies.

our funding

Ellisen Lab partners

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