Photo of Karen Cichowski,  PhD

Karen Cichowski, PhD

Brigham And Women's Hospital

Brigham And Women's Hospital
Phone: (617) 525-4722
Fax: (617) 525-4705

Karen Cichowski, PhD

Brigham And Women's Hospital


  • Associate Professor, Medicine, Harvard Medical School
  • Associate Professor, Genetics, Brigham And Women's Hospital
  • Associate Professor, Medicine/Genetics, Brigham And Women's Hospital



  • Associate Director, Planning and Evaluation, Executive Committee
  • Chair, Center Scientific Council

Research Abstract

The focus of my laboratory is to elucidate how deregulated cell signaling drives cancer. To achieve this we have been taking a multi-faceted approach; combining mouse modeling techniques with basic biochemical and cell biological studies. One of the most commonly deregulated signaling pathways in human cancer is the Ras pathway. Mutations can occur in Ras itself, upstream regulators, or downstream effectors. Therefore we have been focusing on how this pathway promotes nervous system, lung, prostate, and breast cancers. We have also been using our mouse models and insight to develop novel therapies, several of which have been developed into clinical trials.


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  • Lock R, Cichowski K. Loss of negative regulators amplifies RAS signaling. Nat Genet 2015; 47:426-7. PubMed
  • Montero J, Sarosiek KA, DeAngelo JD, Maertens O, Ryan J, Ercan D, Piao H, Horowitz NS, Berkowitz RS, Matulonis U, Jänne PA, Amrein PC, Cichowski K, Drapkin R, Letai A. Drug-induced death signaling strategy rapidly predicts cancer response to chemotherapy. Cell 2015; 160:977-89. PubMed
  • De Raedt T, Beert E, Pasmant E, Luscan A, Brems H, Ortonne N, Helin K, Hornick JL, Mautner V, Kehrer-Sawatzki H, Clapp W, Bradner J, Vidaud M, Upadhyaya M, Legius E, Cichowski K. PRC2 loss amplifies Ras-driven transcription and confers sensitivity to BRD4-based therapies. Nature 2014; 514:247-51. PubMed
  • Malone CF, Fromm JA, Maertens O, De Raedt T, Ingraham R, Cichowski K. Defining key signaling nodes and therapeutic biomarkers in NF1-mutant cancers. 2014. PubMed
  • Maertens O, Cichowski K. An expanding role for RAS GTPase activating proteins (RAS GAPs) in cancer. Adv Biol Regul 2014; 55C:1-14. PubMed
  • Maertens O, Cichowski K. Paths of resistance to EGFR inhibitors: is NF enough? 2014; 4:519-21. PubMed
  • Widemann BC, Acosta MT, Ammoun S, Belzberg AJ, Bernards A, Blakeley J, Bretscher A, Cichowski K, Clapp DW, Dombi E, Evans GD, Ferner R, Fernandez-Valle C, Fisher MJ, Giovannini M, Gutmann DH, Hanemann CO, Hennigan R, Huson S, Ingram D, Kissil J, Korf BR, Legius E, Packer RJ, McClatchey AI, McCormick F, North K, Pehrsson M, Plotkin SR, Ramesh V, Ratner N, Schirmer S, Sherman L, Schorry E, Stevenson D, Stewart DR, Ullrich N, Bakker AC, Morrison H. CTF meeting 2012: Translation of the basic understanding of the biology and genetics of NF1, NF2, and schwannomatosis toward the development of effective therapies. Am J Med Genet A 2014; 164A:563-78. PubMed
  • McLaughlin SK, Olsen SN, Dake B, De Raedt T, Lim E, Bronson RT, Beroukhim R, Polyak K, Brown M, Kuperwasser C, Cichowski K. The RasGAP gene, RASAL2, is a tumor and metastasis suppressor. Cancer Cell 2013; 24:365-78. PubMed
  • Hollstein PE, Cichowski K. Identifying the ubiquitin ligase complex that regulates the NF1 tumor suppressor and Ras. 2013. PubMed
  • Maertens O, Johnson B, Hollstein P, Frederick DT, Cooper ZA, Messaien L, Bronson RT, McMahon M, Granter S, Flaherty KT, Wargo JA, Marais R, Cichowski K. Elucidating distinct roles for NF1 in melanomagenesis. 2012. PubMed
  • McClatchey AI, Cichowski K. SPRED proteins provide a NF-ty link to Ras suppression. Genes Dev 2012; 26:1515-9. PubMed
  • Beert E, Brems H, Daniëls B, De Wever I, Van Calenbergh F, Schoenaers J, Debiec-Rychter M, Gevaert O, De Raedt T, Van Den Bruel A, de Ravel T, Cichowski K, Kluwe L, Mautner V, Sciot R, Legius E. Atypical neurofibromas in neurofibromatosis type 1 are premalignant tumors. Genes Chromosomes Cancer 2011; 50:1021-32. PubMed
  • De Raedt T, Walton Z, Yecies JL, Li D, Chen Y, Malone CF, Maertens O, Jeong SM, Bronson RT, Lebleu V, Kalluri R, Normant E, Haigis MC, Manning BD, Wong KK, Macleod KF, Cichowski K. Exploiting cancer cell vulnerabilities to develop a combination therapy for ras-driven tumors. Cancer Cell 2011; 20:400-13. PubMed
  • Huson SM, Acosta MT, Belzberg AJ, Bernards A, Chernoff J, Cichowski K, Gareth Evans D, Ferner RE, Giovannini M, Korf BR, Listernick R, North KN, Packer RJ, Parada LF, Peltonen J, Ramesh V, Reilly KM, Risner JW, Schorry EK, Upadhyaya M, Viskochil DH, Zhu Y, Hunter-Schaedle K, Giancotti FG. Back to the future: proceedings from the 2010 NF Conference. Am J Med Genet A 2011; 155:307-21. PubMed
  • Cichowski K, Jänne PA. Drug discovery: inhibitors that activate. Nature 2010; 464:358-9. PubMed
  • Min J, Zaslavsky A, Fedele G, McLaughlin SK, Reczek EE, De Raedt T, Guney I, Strochlic DE, Macconaill LE, Beroukhim R, Bronson RT, Ryeom S, Hahn WC, Loda M, Cichowski K. An oncogene-tumor suppressor cascade drives metastatic prostate cancer by coordinately activating Ras and nuclear factor-kappaB. Nat Med 2010; 16:286-94. PubMed
  • McGillicuddy LT, Fromm JA, Hollstein PE, Kubek S, Beroukhim R, De Raedt T, Johnson BW, Williams SM, Nghiemphu P, Liau LM, Cloughesy TF, Mischel PS, Parret A, Seiler J, Moldenhauer G, Scheffzek K, Stemmer-Rachamimov AO, Sawyers CL, Brennan C, Messiaen L, Mellinghoff IK, Cichowski K. Proteasomal and genetic inactivation of the NF1 tumor suppressor in gliomagenesis. Cancer Cell 2009; 16:44-54. PubMed
  • Cichowski K,Hahn WC. Unexpected pieces to the senescence puzzle. Cell 2008; 133:958-61. PubMed
  • Courtois-Cox S, Jones SL, Cichowski K. Many roads lead to oncogene-induced senescence. Oncogene 2008; 27:2801-9. PubMed
  • Johannessen CM, Johnson BW, Williams SM, Chan AW, Reczek EE, Lynch RC, Rioth MJ, McClatchey A, Ryeom S, Cichowski K. TORC1 is essential for NF1-associated malignancies. Curr Biol 2008; 18:56-62. PubMed
  • Courtois-Cox S, Genther Williams SM, Reczek EE, Johnson BW, McGillicuddy LT, Johannessen CM, Hollstein PE, MacCollin M, Cichowski K. A negative feedback signaling network underlies oncogene-induced senescence. Cancer Cell 2006; 10:459-72. PubMed
  • Johannessen CM, Reczek EE, James MF, Brems H, Legius E, Cichowski K. The NF1 tumor suppressor critically regulates TSC2 and mTOR. Proc Natl Acad Sci U S A 2005; 102:8573-8. PubMed
  • Engelman JA, J. ErbB-3 mediates phosphoinositide 3-kinase activity in gefitinib-sensitive non-small cell lung cancer cell lines. Proc Natl Acad Sci U S A 2005; 102:3788-93. PubMed
  • Cichowski K, Santiago S, Jardim M, Johnson BW, Jacks T. Dynamic regulation of the Ras pathway via proteolysis of the NF1 tumor suppressor. Genes Dev 2003; 17:449-54. PubMed
  • Cichowski K, Jacks T. NF1 tumor suppressor gene function: narrowing the GAP. Cell 2001; 104:593-604. PubMed
  • Cichowski K, Shih TS, Schmitt E, Santiago S, Reilly K, McLaughlin ME, Bronson RT, Jacks T. Mouse models of tumor development in neurofibromatosis type 1. Science 1999; 286:2172-6. PubMed