Cigall Kadoch, Ph.D.


My laboratory investigates how disruption of a protein complex that governs DNA architecture and gene expression can lead to cancer. By controlling whether regions of the genome are completely compact or relatively accessible, groups of proteins called chromatin-remodeling complexes regulate gene activity-- including the activity of genes that can promote cancer. We have discovered that mutations in the genes encoding the protein subunits of one such chromatin-remodeling complex, the BAF complex, occur in more than one-fifth of all human cancers. As a graduate student, I discovered the underlying mechanism of a rare but aggressive cancer called synovial sarcoma, for which BAF complex perturbation is the driving oncogenic event in 100% of cases. This has provided a strong foundation upon which to interrogate the mechanistic basis for BAF complex compromise in human cancer. Combining biochemistry, structural and molecular biology, functional genomics and now chemistry, my team studies how this protein complex is pieced together in cells and aims to identify molecules that can restore proper assembly and function in cancer cells with BAF complex mutations. These results may potentially yield a new class of cancer therapeutics.

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