Cigall Kadoch is an Assistant Professor of Pediatric Oncology at the Dana-Farber Cancer Institute and Harvard Medical School
and an Institute Member of the Broad Institute of MIT and Harvard. Dr. Kadoch studies chromatin regulation, with strong focus on the structure and function of the mammalian SWI/SNF or BAF family
of chromatin remodeling complexes in human cancer. Her work has been centered in mechanistically interrogating rare, molecularly well-defined cancers, to understand the role these complexes play
in promoting a wide range of more common cancer types.
Kadoch completed her graduate and postdoctoral research at the Stanford University School of Medicine. Working alongside
renowned developmental biologist Gerald Crabtree, she used a series of biochemical experiments to identify a novel set of proteins, components of the mSWI/SNF or BAF complex, which regulate
chromatin structure. Upon these discoveries, Kadoch and her colleagues then linked mutations in the subunits of BAF complexes to more than one-fifth of human cancers. In addition, she worked to
uncover the precise mechanism of BAF complex perturbation in a rare, aggressive soft-tissue sarcoma, known as synovial sarcoma. Kadoch is now developing new approaches to the structural and
functional interrogation of chromatin regulators and developing therapeutic approaches for cancers driven by BAF mutations.
Kadoch earned her undergraduate degree in Molecular and Cell Biology from the University of California, Berkeley, and her
Ph.D. in Cancer Biology from the Stanford University School of Medicine. In 2014, shortly before becoming one of the youngest Assistant Professors ever appointed to the faculty of Harvard Medical
School, she was named to Forbes Magazine’s 30 Under 30 in Science & Healthcare, and in 2015, the MIT Technology Review Top Innovators Under 35.
She is also the recipient of the NIH Director’s New Innovator Award and was recently named a Pew-Stewart Scholar in Cancer Research.
Mammalian SWI/SNF (BAF) complex structure and function in human cancer
Exome- and genome-wide sequencing studies in human cancer have revealed a striking frequency of mutations in the genes encoding subunits of the mammalian SWI/SNF (BAF) family of ATP-dependent
chromatin remodeling complexes. We recently determined these mutations to be broadly recurrent in over 20% of all cancers. Here, we present studies focused on BAF complex assembly and
architecture, cancer-specific complex subunit and associated protein factor composition, and novel approaches toward the identification of small molecule therapeutics for this class of human
To investigate the underlying mechanism, our group has studied genomically well-defined cancer types driven by both gain- and loss-of-function mutations to genes encoding BAF complex subunit or associated factors. These include human synovial sarcoma (SS) in which 100% of tumors have a precise translocation involving the SS18 subunit, malignant rhabdoid tumors which are driven by deletion of the BAF47 (SMARCB1) subunit, and more recently cancers driven by aberrant activation of transcription factors which bind to and direct BAF complex targeting. Taken together, the study of BAF complex-
mediated oncogenesis in these disease settings has provided us with a powerful foundation upon which to understand the precise oncogenic mechanisms directed by altered subunit composition, structure and function of chromatin remodeling complex.