Cichowski Lab

Brigham & Women's Hospital | Harvard Medical School

The NF1 tumor suppressor

NF1 was the first RasGAP gene shown to function as a human tumor suppressor.  It is inactivated in a common familial cancer syndrome, affecting 1 in 3500 individuals. NF1 patients can develop numerous peripheral nervous system tumors and are also predisposed to developing brain tumors, myeloid malignancies, and cognitive deficits. However, we and others have found that the NF1 gene is also mutated in a variety of sporadic cancers, including glioblastoma. We have been focusing on understanding how this enigmatic tumor suppressor functions on a cellular level in tumors that develop in NF1 patients, and sporadic tumors, and have been exploiting this insight to develop new targeted cancer therapies.


MAPK Pathway Suppression Unmasks Latent DNA Repair Defects and Confers a Chemical Synthetic Vulnerability in BRAF-, NRAS-, and NF1-Mutant Melanomas

Ophélia Maertens, Ryan Kuzmickas, Haley E. Manchester, Chloe E. Emerson, Alessandra G. Gavin, Caroline J. Guild, Terence C. Wong, Thomas De Raedt, Christian Bowman-Colin, Elodie Hatchi, Levi A. Garraway, Keith T. Flaherty, Shailja Pathania, Stephen J. Elledge, Karen Cichowski

Cancer Discovery, vol. 9, 2019 Apr, pp. 526-545

Cotargeting MNK and MEK kinases induces the regression of NF1-mutant cancers

Rebecca Lock, Rachel Ingraham, Ophélia Maertens, Abigail L. Miller, Nelly Weledji, Eric Legius, Bruce M. Konicek, Sau-Chi B. Yan, Jeremy R. Graff, Karen Cichowski

The Journal of Clinical Investigation, vol. 126, The American Society for Clinical Investigation, 2016 Jun, pp. 2181-2190


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