DF/HCC Program Affiliation

Member, Cancer Genetics Program
Member, Kidney Cancer Program
Member, Breast Cancer Program

DF/HCC Associations

Deputy Associate Director, Program Development, EC
Institutional Representative for MGH, Executive Committee
Member, Center Scientific Council

Research Abstract

My laboratory is interested in the genetics of cancer, with particular emphasis on studying genetic predisposition and on characterizing tumor suppressor genes involved in Wilms tumor and breast cancer. The Wilms tumor suppressor WT1 encodes a zinc finger transcription factor that is critical to kidney development. We have used hybridization to high density microarrays to identify transcriptional targets of WT1 and define potential functional pathways. We have employed similar strategies to search for downstream targets of the breast cancer susceptibility gene BRCA1. The laboratory is also engaged in high throughput mutational detection strategies to search for alterations in novel genes that may be involved in genetic predisposition to breast cancer.

Publications

• Haber DA, Settleman J. Cancer: drivers and passengers. Nature 2007 Mar 8; 446(7132):145-6
  PMID: 17344839
• Mulloy R, Ferrand A, Kim Y, Sordella R, Bell DW, Haber DA, Anderson KS, Settleman J. Epidermal growth factor receptor mutants from human lung cancers exhibit enhanced catalytic activity and increased sensitivity to gefitinib. Cancer Res 2007 Mar 1; 67(5):2325-30
  PMID: 17332364
• Sharma SV, Bell DW, Settleman J, Haber DA. Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer 2007 Mar; 7(3):169-81
  PMID: 17318210
• Erkko H, Xia B, Nikkilä J, Schleutker J, Syrjäkoski K, Mannermaa A, Kallioniemi A, Pylkäs K, Karppinen SM, Rapakko K, Miron A, Sheng Q, Li G, Mattila H, Bell DW, Haber DA, Grip M, Reiman M, Jukkola-Vuorinen A, Mustonen A, Kere J, Aaltonen LA, Kosma VM, Ka. A recurrent mutation in PALB2 in Finnish cancer families. Nature 2007 Mar 15; 446(7133):316-9
  PMID: 17287723
• Rivera MN, Kim WJ, Wells J, Driscoll DR, Brannigan BW, Han M, Kim JC, Feinberg AP, Gerald WL, Vargas SO, Chin L, Iafrate AJ, Bell DW, Haber DA. An X chromosome gene, WTX, is commonly inactivated in Wilms tumor. Science 2007 Feb 2; 315(5812):642-5
  PMID: 17204608
• Sharma SV, Gajowniczek P, Way IP, Lee DY, Jiang J, Yuza Y, Classon M, Haber DA, Settleman J. A common signaling cascade may underlie "addiction" to the Src, BCR-ABL, and EGF receptor oncogenes. Cancer Cell 2006 Nov; 10(5):425-35
  PMID: 17097564
• Overholtzer M, Zhang J, Smolen GA, Muir B, Li W, Sgroi DC, Deng CX, Brugge JS, Haber DA. Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon. Proc Natl Acad Sci U S A 2006 Aug 15; 103(33):12405-10
  PMID: 16894141
• Haber DA, Bell DW, Sordella R, Kwak EL, Godin-Heymann N, Sharma SV, Lynch TJ, Settleman J. Molecular targeted therapy of lung cancer: EGFR mutations and response to EGFR inhibitors. Cold Spring Harb Symp Quant Biol 2005; 70:419-26
  PMID: 16869779
• Sharma SV, Fischbach MA, Haber DA, Settleman J. "Oncogenic Shock": Explaining Oncogene Addiction through Differential Signal Attenuation. Clin Cancer Res 2006 Jul 15; 12(14):4392s-5s
  PMID: 16857816
• Kwak EL, Jankowski J, Thayer SP, Lauwers GY, Brannigan BW, Harris PL, Okimoto RA, Haserlat SM, Driscoll DR, Ferry D, Muir B, Settleman J, Fuchs CS, Kulke MH, Ryan DP, Clark JW, Sgroi DC, Haber DA, Bell DW. Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas. Clin Cancer Res 2006 Jul 15; 12(14 Pt 1):4283-7
  PMID: 16857803
• Bell DW, Haber DA. A blood-based test for epidermal growth factor receptor mutations in lung cancer. Clin Cancer Res 2006 Jul 1; 12(13):3875-7
  PMID: 16818680
• Diederichs S, Haber DA. Sequence variations of microRNAs in human cancer: alterations in predicted secondary structure do not affect processing. Cancer Res 2006 Jun 15; 66(12):6097-104
  PMID: 16778182
• Smolen GA, Muir B, Mohapatra G, Barmettler A, Kim WJ, Rivera MN, Haserlat SM, Okimoto RA, Kwak E, Dahiya S, Garber JE, Bell DW, Sgroi DC, Chin L, Deng CX, Haber DA. Frequent met oncogene amplification in a Brca1/Trp53 mouse model of mammary tumorigenesis. Cancer Res 2006 Apr 1; 66(7):3452-5
  PMID: 16585167
• Kwak EL, Kim S, Zhang J, Cardiff RD, Schmidt EV, Haber DA. Mammary tumorigenesis following transgenic expression of a dominant negative CHK2 mutant. Cancer Res 2006 Feb 15; 66(4):1923-8
  PMID: 16488990
• Smolen GA, Sordella R, Muir B, Mohapatra G, Barmettler A, Archibald H, Kim WJ, Okimoto RA, Bell DW, Sgroi DC, Christensen JG, Settleman J, Haber DA. Amplification of MET may identify a subset of cancers with extreme sensitivity to the selective tyrosine kinase inhibitor PHA-665752. Proc Natl Acad Sci U S A 2006 Feb 14; 103(7):2316-21
  PMID: 16461907
• Bell DW, Gore I, Okimoto RA, Godin-Heymann N, Sordella R, Mulloy R, Sharma SV, Brannigan BW, Mohapatra G, Settleman J, Haber DA. Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR. Nat Genet 2005 Dec; 37(12):1315-6
  PMID: 16258541
• Lorenzen JA, Bonacci BB, Palmer RE, Wells C, Zhang J, Haber DA, Goldstein AM, Mayer AN. Rbm19 is a nucleolar protein expressed in crypt/progenitor cells of the intestinal epithelium. Gene Expr Patterns 2005 Dec; 6(1):45-56
  PMID: 16027046
• Lee SB, Huang K, Palmer R, Truong VB, Herzlinger D, Kolquist KA, Wong J, Paulding C, Yoon SK, Gerald W, Oliner JD, Haber DA. The Wilms tumor suppressor WT1 encodes a transcriptional activator of amphiregulin. Cell 1999 Sep 3; 98(5):663-73
  PMID: 10490105
• Harkin DP, Bean JM, Miklos D, Song YH, Truong VB, Englert C, Christians FC, Ellisen LW, Maheswaran S, Oliner JD, Haber DA. Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1. Cell 1999 May 28; 97(5):575-86
  PMID: 10367887
• FitzGerald MG, MacDonald DJ, Krainer M, Hoover I, O'Neil E, Unsal H, Silva-Arrieto S, Finkelstein DM, Beer-Romero P, Englert C, Sgroi DC, Smith BL, Younger JW, Garber JE, Duda RB, Mayzel KA, Isselbacher KJ, Friend SH, Haber DA. Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer. N Engl J Med 1996 Jan 18; 334(3):143-9
  PMID: 8531968