Cigall Kadoch

Introduction & Background:

Dr. Cigall Kadoch is an Associate Professor of Pediatric Oncology at the Dana-Farber Cancer Institute, an affiliated faculty member of the Biological Chemistry and Molecular Pharmacology department at Harvard Medical School, as well as an Institute Member and Epigenomics Program Co-Director at the Broad Institute of MIT and Harvard. In addition to her academic positions, she is the founder of Foghorn Therapeutics, a company that is developing targeted gene therapies using their Gene Traffic ControlTM Product Platform. 

Dr. Kadoch earned her B.A. in Molecular and Cellular Biology at the University of California, Berkeley, and earned her Ph.D. in Cancer Biology at the Stanford University School of Medicine in the laboratory of Gerald Crabtree. Her research is primarily focused on understanding the role of chromatin remodeling complexes in cancer biology. 

Early Career and first discoveries:

Following the surge of whole exome and genome sequencing datasets of cancer cell lines and tissues at the end of the 2000s, it became clear that many of the most commonly mutated genes in cancer were components of protein complexes which were responsible for various aspects of gene expression control. Under the supervision of Dr. Gerald Crabtree, Dr. Kadoch’ thesis work was focused on studying one of these protein complexes, the mammalian SWI/SNF homologs, known in humans as BAF complexes. While this complex is normally utilized to maintain the proper control of gene expression, Dr. Kadoch found that a specific component of this complex was ubiquitously mutated in a rare and obscure cancer, synovial sarcoma. 

This particular mutation, a translocation which fused a component of the BAF complex with another protein, was then shown to be causative of this rare cancer, and the mechanism by which it transformed this malignancy was meticulously unraveled by Dr. Kadoch. Soon after her discoveries in synovial sarcoma, it became evident this finding was not a unique incidence, but rather a widespread and recurrent phenomenon across a variety of cancers, including many of those most common. Mining additional datasets showed that various components of the BAF complexes were mutated in over 20% of human cancers, making it the most mutated epigenetic protein complex across all cancer types. 

Her work on the BAF complex’ role in synovial sarcoma led to the publishing of two high impact papers back to back in 2013, and set a grand stage for Dr. Kadoch’s career moving forward.

Becoming an Independent Investigator & The Future:

Due to her extraordinarily achievements during her graduate studies, rather than following the traditional trajectory of continuing on to do a post-doctoral fellowship she was offered a faculty position as an Assistant Professor of Pediatric Oncology at the Dana-Farber Institute. She became an independent investigator of her own research laboratory at the age of 28, making her one of the youngest faculty members at the Dana-Farber Institute and affiliate faculty of Harvard Medical school. Since her landmark discoveries in the context of synovial sarcoma, she has expanded her research program into many other forms of malignancies, such as liver, prostate, and breast cancers. 

Her laboratory continues to use novel and innovative methodologies to meticulously dissect the mechanisms by which different BAF complexes contribute to various cancers. Specifically, her lab is at the forefront of combining powerful genetic screens with intricate biochemistry to assess structure-function relationships of different components of these protein complexes. In addition to its role in cancer initiation and progression, her lab has also contributed tremendously to the basic understanding of BAF’s modular assembly and mechanistic function.

In 2018 Dr. Kadoch co-founded Foghorn Theraputics, a biotechnology company focused on using their Gene Traffic ControlTM Product Platform to transform the science they discover in the lab into real life human therapies. While starting this company, Dr. Kadoch was able to raise $50 million in initial capital investment from the life science funding enterprise Flagship Pioneering.

From academia to industry, Dr. Kadoch’ career has moved at a nearly unbelievable pace. Her immense passion and drive has been clearly demonstrated by her consistent and impressive accomplishments, and she is undoubtedly an inspiration and role model for many young scientists beginning their career. 

Significant Publications:

Reversible disruption of mSWI/SNF (BAF) complexes by the SS18-SSX oncogenic fusion in synovial sarcoma (Cell, 2013) https://www.sciencedirect.com/science/article/pii/S0092867413002687?via%3Dihub

Proteomic and bioinformatic analysis of the mammalian SWI/SNF complexes identifies extensive roles in human malignancy (Nature Genetics, 2013) https://www.nature.com/articles/ng.2628

Dynamics of BAF-Polycomb complex opposition on heterochromatin in normal and oncogenic states (Nature Genetics, 2017) https://www.nature.com/articles/ng.3734

SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters (Nature Genetics, 2017) https://www.nature.com/articles/ng.3958

Interrogation of Mammalian Protein Complex Structure, Function, and Membership Using Genome-Scale Fitness Screens (Cell Systems, 2018) https://www.sciencedirect.com/science/article/pii/S240547121830187X?via%3Dihub

Significant Achievements & Honors:

2014 Forbes 30 under 30: 

https://www.forbes.com/sites/sarahhedgecock/2014/10/01/fighting-cancer-by-fixing-our-cells-hard-drives/#337b7b344b72

2014 NIH Director’s New Innovator Award 2014: https://commonfund.nih.gov/newinnovator/awardrecipients14

2015 Pew Scholar Award: https://www.pewtrusts.org/en/projects/pew-stewart-scholars-for-cancer-research/directory-of-stewart-scholars/2015/cigall-kadoch

2015 MIT Technology Review’s 35 Innovators Under 35: https://www.technologyreview.com/video/meet-the-innovators-under-35-cigall-kadoch-dana-farber-cancer-institute-and-harvard-medical-school/

2017 Business Insider’s Top 30 Young Leaders in Biopharma: https://www.businessinsider.com/30-under-40-leaders-in-biotech-pharma-2017-10

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