DF/HCC Program Affiliation

Cancer Genetics
Gastrointestinal Malignancies

Research Abstract

We are involved in generating mouse models for human cancer and studying the roles of genes implicated in cancer initiation and progression. We use gene targeting to generate genetically modified mice. We have made mice with mutations in Apc, Mcc, N-ras, Smad2, Smad4, Msh2, Msh3, Msh4, Msh5, Msh6 and Mlh1. Many of these mice are predisposed to develop cancer at a number of anatomical sites, most frequently in the gastrointestinal tract. Some of these mice individually or in combinations are excellent models for familial adenomatous polyposis (FAP) and hereditary non-polyposis colon cancer (HNPCC). We are currently examining the role of a number of other genes in the initiation and progression of a number of cancers with emphasis on gastrointestinal cancer.

Publications

• Kucherlapati M, Nguyen A, Kuraguchi M, Yang K, Fan K, Bronson R, Wei K, Lipkin M, Edelmann W, Kucherlapati R.Tumor progression in Apc(1638N) mice with Exo1 and Fen1 deficiencies.Oncogene 2007 Apr 23.
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• Kratz CP, Niemeyer CM, Thomas C, Bauhuber S, Matejas V, Bergstrasser E, Flotho C, Flores NJ, Haas O, Hasle H, van den Heuvel-Eibrink MM, Kucherlapati RS, Lang P, Roberts AE, Stary J, Strahm B, Swanson KD, Trebo M, Zecca M, Neel B, Locatelli F, Loh ML, Zen
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• Roberts AE, Araki T, Swanson KD, Montgomery KT, Schiripo TA, Joshi VA, Li L, Yassin Y, Tamburino AM, Neel BG, Kucherlapati RS.Germline gain-of-function mutations in SOS1 cause Noonan syndrome.Nat Genet 2007 Jan;39(1):70-4.
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• Joshi VA, Kucherlapati R.Lung cancer genetics and pharmacogenomics.Cytogenet Genome Res 2006;115(3-4):298-302.
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• Dumstorf CA, Clark AB, Lin Q, Kissling GE, Yuan T, Kucherlapati R, McGregor WG, Kunkel TA.Participation of mouse DNA polymerase iota in strand-biased mutagenic bypass of UV photoproducts and suppression of skin cancer.Proc Natl Acad Sci U S A 2006 Nov 28;
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• Kuraguchi M, Wang XP, Bronson RT, Rothenberg R, Ohene-Baah NY, Lund JJ, Kucherlapati M, Maas RL, Kucherlapati R.Adenomatous polyposis coli (APC) is required for normal development of skin and thymus.PLoS Genet 2006 Sep 15;2(9):e146.
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• Scherer SE, Muzny DM, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Montgomery KT,
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• Moran JL, Bolton AD, Tran PV, Brown A, Dwyer ND, Manning DK, Bjork BC, Li C, Montgomery K, Siepka SM, Vitaterna MH, Takahashi JS, Wiltshire T, Kwiatkowski DJ, Kucherlapati R, Beier DR.Utilization of a whole genome SNP panel for efficient genetic mapping i
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• Klein J, Ju W, Heyer J, Wittek B, Haneke T, Knaus P, Kucherlapati R, Böttinger EP, Nitschke L, Kneitz B.B cell-specific deficiency for Smad2 in vivo leads to defects in TGF-beta-directed IgA switching and changes in B cell fate.J Immunol 2006 Feb 15;176(4
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• Lin DP, Wang Y, Scherer SJ, Clark AB, Yang K, Avdievich E, Jin B, Werling U, Parris T, Kurihara N, Umar A, Kucherlapati R, Lipkin M, Kunkel TA, Edelmann W.An Msh2 point mutation uncouples DNA mismatch repair and apoptosis.Cancer Res 2004 Jan 15;64(2):517-
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• Costa RM, Federov NB, Kogan JH, Murphy GG, Stern J, Ohno M, Kucherlapati R, Jacks T, Silva AJ.Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1.Nature 2002 Jan 31;415(6871):526-30.
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• Merscher S, Funke B, Epstein JA, Heyer J, Puech A, Lu MM, Xavier RJ, Demay MB, Russell RG, Factor S, Tokooya K, Jore BS, Lopez M, Pandita RK, Lia M, Carrion D, Xu H, Schorle H, Kobler JB, Scambler P, Wynshaw-Boris A, Skoultchi AI, Morrow BE, Kucherlapati
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• Montgomery KT, Lee E, Miller A, Lau S, Shim C, Decker J, Chiu D, Emerling S, Sekhon M, Kim R, Lenz J, Han J, Ioshikhes I, Renault B, Marondel I, Yoon SJ, Song K, Murty VV, Scherer S, Yonescu R, Kirsch IR, Ried T, McPherson J, Gibbs R, Kucherlapati R.A hig
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