DF/HCC Program Affiliation

Member, Prostate Cancer Program
Member, Neuro-Oncology Program
Member, Cancer Genetics Program
Member, Gastrointestinal Malignancies Program
Member, Cutaneous Oncology and Melanoma Program

Research Abstract

Our research focuses on mechanisms governing normal development and aging and cancer pathogenesis. The complexities of these biological processes are viewed on several levels-molecular, cellular, and organismal-with the ultimate goal of integrating the lessons learned from each approach. These studies evaluate the roles played by growth promoting oncogenes (the Myc family), by tumor suppressor genes that constrain growth and/or stimulate differentiation (Rb, p53, Mad and CKIs), and telomerase. Significant effort is devoted towards the construction of mouse models of human cancer, particularly melanoma, prostate, and brain.

Publications

• Maser RS, Choudhury B, Campbell PJ, Feng B, Wong KK, Protopopov A, O'neil J, Gutierrez A, Ivanova E, Perna I, Lin E, Mani V, Jiang S, McNamara K, Zaghlul S, Edkins S, Stevens C, Brennan C, Martin ES, Wiedemeyer R, Kabbarah O, Nogueira C, Histen G, Aster J. Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature 2007 May 21;
  PMID: 17515920
• Carrasco DR, Sukhdeo K, Protopopova M, Sinha R, Enos M, Carrasco DE, Zheng M, Mani M, Henderson J, Pinkus GS, Munshi N, Horner J, Ivanova EV, Protopopov A, Anderson KC, Tonon G, DePinho RA. The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis. Cancer Cell 2007 Apr; 11(4):349-60
  PMID: 17418411
• Khoo CM, Carrasco DR, Bosenberg MW, Paik JH, Depinho RA. Ink4a/Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse. Proc Natl Acad Sci U S A 2007 Mar 6; 104(10):3931-6
  PMID: 17360455
• Podar K, Raab MS, Tonon G, Sattler M, Barilà D, Zhang J, Tai YT, Yasui H, Raje N, Depinho RA, Hideshima T, Chauhan D, Anderson KC. Up-Regulation of c-Jun Inhibits Proliferation and Induces Apoptosis via Caspase-Triggered c-Abl Cleavage in Human Multiple Myeloma. Cancer Res 2007 Feb 15; 67(4):1680-1688
  PMID: 17308109
• Ligon KL, Huillard E, Mehta S, Kesari S, Liu H, Alberta JA, Bachoo RM, Kane M, Louis DN, Depinho RA, Anderson DJ, Stiles CD, Rowitch DH. Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma. Neuron 2007 Feb 15; 53(4):503-17
  PMID: 17296553
• Chu GC, Kimmelman AC, Hezel AF, Depinho RA. Stromal biology of pancreatic cancer. J Cell Biochem 2007 Jan 31;
  PMID: 17266048
• Tothova Z, Kollipara R, Huntly BJ, Lee BH, Castrillon DH, Cullen DE, McDowell EP, Lazo-Kallanian S, Williams IR, Sears C, Armstrong SA, Passegué E, DePinho RA, Gilliland DG. FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress. Cell 2007 Jan 26; 128(2):325-39
  PMID: 17254970
• Paik JH, Kollipara R, Chu G, Ji H, Xiao Y, Ding Z, Miao L, Tothova Z, Horner JW, Carrasco DR, Jiang S, Gilliland DG, Chin L, Wong WH, Castrillon DH, DePinho RA. FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis. Cell 2007 Jan 26; 128(2):309-23
  PMID: 17254969
• Sharpless NE, DePinho RA. Cancer biology: gone but not forgotten. Nature 2007 Feb 8; 445(7128):606-7
  PMID: 17251931
• Li H, Liang J, Castrillon DH, DePinho RA, Olson EN, Liu ZP. FoxO4 regulates tumor necrosis factor alpha-directed smooth muscle cell migration by activating matrix metalloproteinase 9 gene transcription. Mol Cell Biol 2007 Apr; 27(7):2676-86
  PMID: 17242183
• Farazi PA, DePinho RA. The genetic and environmental basis of hepatocellular carcinoma. Discov Med 2006 Oct; 6(35):182-6
  PMID: 17234139
• Stegh AH, Kim H, Bachoo RM, Forloney KL, Zhang J, Schulze H, Park K, Hannon GJ, Yuan J, Louis DN, DePinho RA, Chin L. Bcl2L12 inhibits post-mitochondrial apoptosis signaling in glioblastoma. Genes Dev 2007 Jan 1; 21(1):98-111
  PMID: 17210792
• Maher EA, Brennan C, Wen PY, Durso L, Ligon KL, Richardson A, Khatry D, Feng B, Sinha R, Louis DN, Quackenbush J, Black PM, Chin L, DePinho RA. Marked genomic differences characterize primary and secondary glioblastoma subtypes and identify two distinct molecular and clinical secondary glioblastoma entities. Cancer Res 2006 Dec 1; 66(23):11502-13
  PMID: 17114236
• Bardeesy N, Cheng KH, Berger JH, Chu GC, Pahler J, Olson P, Hezel AF, Horner J, Lauwers GY, Hanahan D, DePinho RA. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev 2006 Nov 15; 20(22):3130-46
  PMID: 17114584
• Liu F, Park PJ, Lai W, Maher E, Chakravarti A, Durso L, Jiang X, Yu Y, Brosius A, Thomas M, Chin L, Brennan C, DePinho RA, Kohane I, Carroll RS, Black PM, Johnson MD. A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma. Cancer Res 2006 Nov 15; 66(22):10815-23
  PMID: 17090523
• Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, Cheng T, DePinho RA, Sharpless NE, Scadden DT. Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a. Nature 2006 Sep 28; 443(7110):421-6
  PMID: 16957735
• Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer 2006 Sep; 6(9):674-87
  PMID: 16929323
• Sharpless NE, Depinho RA. The mighty mouse: genetically engineered mouse models in cancer drug development. Nat Rev Drug Discov 2006 Sep; 5(9):741-54
  PMID: 16915232
• Farazi PA, Zeisberg M, Glickman J, Zhang Y, Kalluri R, DePinho RA. Chronic bile duct injury associated with fibrotic matrix microenvironment provokes cholangiocarcinoma in p53-deficient mice. Cancer Res 2006 Jul 1; 66(13):6622-7
  PMID: 16818635
• Dickie R, Bachoo RM, Rupnick MA, Dallabrida SM, Deloid GM, Lai J, Depinho RA, Rogers RA. Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy. Microvasc Res 2006 Jul-Sep; 72(1-2):20-6
  PMID: 16806289
• David G, Dannenberg JH, Simpson N, Finnerty PM, Miao L, Turner GM, Ding Z, Carrasco R, Depinho RA. Haploinsufficiency of the mSds3 chromatin regulator promotes chromosomal instability and cancer only upon complete neutralization of p53. Oncogene 2006 Jun 12;
  PMID: 16767157
• Carrasco DR, Tonon G, Huang Y, Zhang Y, Sinha R, Feng B, Stewart JP, Zhan F, Khatry D, Protopopova M, Protopopov A, Sukhdeo K, Hanamura I, Stephens O, Barlogie B, Anderson KC, Chin L, Shaughnessy JD, Brennan C, Depinho RA. High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients. Cancer Cell 2006 Apr; 9(4):313-25
  PMID: 16616336