RONALD ANTHONY DEPINHO

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice
    Mariela Jaskelioff
    Belfer Institute for Applied Cancer Science and Departments of Medical Oncology, Medicine and Genetics, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 469:102-6. 2011
  2. pmc Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells
    Boyi Gan
    Belfer Institute for Applied Cancer Science, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 468:701-4. 2010
  3. pmc A mouse plasma peptide atlas as a resource for disease proteomics
    Qing Zhang
    Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Genome Biol 9:R93. 2008
  4. pmc The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis
    Daniel R Carrasco
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, and Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cancer Cell 11:349-60. 2007
  5. ncbi request reprint The age of cancer
    R A DePinho
    Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 408:248-54. 2000
  6. ncbi request reprint What drives intense apoptosis resistance and propensity for necrosis in glioblastoma? A role for Bcl2L12 as a multifunctional cell death regulator
    Alexander H Stegh
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cell Cycle 7:2833-9. 2008
  7. pmc Ink4a/Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse
    Christine M Khoo
    Department of Medical Oncology, Belfer Foundation Institute for Innovative Cancer Science, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:3931-6. 2007
  8. ncbi request reprint Up-regulation of c-Jun inhibits proliferation and induces apoptosis via caspase-triggered c-Abl cleavage in human multiple myeloma
    Klaus Podar
    Jerome Lipper Multiple Myeloma Center, Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Cancer Res 67:1680-8. 2007
  9. ncbi request reprint Telomeres and the DNA damage response: why the fox is guarding the henhouse
    Richard S Maser
    Department of Medical Oncology, Dana Farber Cancer Institute, Departments of Medicine and Genetics, Harvard Medical School, Boston, MA 02115, USA
    DNA Repair (Amst) 3:979-88. 2004
  10. ncbi request reprint Take care of your chromosomes lest cancer take care of you
    Richard S Maser
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 3:4-6. 2003

Research Grants

  1. TELOMERASE IN DEVELOPMENT, SENESCENCE AND NEOPLASIA
    Ronald DePinho; Fiscal Year: 2007
  2. Genetics and Biology of Pancreatic Duct Adenocarcinoma
    Ronald DePinho; Fiscal Year: 2007
  3. Evolution of Primary and Resistant Solid Tumors
    Ronald DePinho; Fiscal Year: 2007
  4. TELOMERASE IN DEVELOPMENT, SENESCENCE AND NEOPLASIA
    Ronald DePinho; Fiscal Year: 2009
  5. Genetics and Biology of Malignant Glioma
    Ronald DePinho; Fiscal Year: 2007
  6. TELOMERASE IN DEVELOPMENT, SENESCENCE AND NEOPLASIA
    Ronald DePinho; Fiscal Year: 2006
  7. TELOMERASE IN DEVELOPMENT, SENESCENCE AND NEOPLASIA
    Ronald DePinho; Fiscal Year: 2005
  8. Conference on Mouse Models of Cancer
    Ronald DePinho; Fiscal Year: 2003
  9. TELOMERASE IN DEVELOPMENT, SENESCENCE AND NEOPLASIA
    RONALD ANTHONY DEPINHO; Fiscal Year: 2010

Detail Information

Publications90

  1. pmc Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice
    Mariela Jaskelioff
    Belfer Institute for Applied Cancer Science and Departments of Medical Oncology, Medicine and Genetics, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 469:102-6. 2011
    ....
  2. pmc Lkb1 regulates quiescence and metabolic homeostasis of haematopoietic stem cells
    Boyi Gan
    Belfer Institute for Applied Cancer Science, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Nature 468:701-4. 2010
    ..Thus, Lkb1 serves as an essential regulator of HSCs and haematopoiesis, and more generally, points to the critical importance of coupling energy metabolism and stem-cell homeostasis...
  3. pmc A mouse plasma peptide atlas as a resource for disease proteomics
    Qing Zhang
    Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Genome Biol 9:R93. 2008
    ..A major finding from this study is the identification of novel isoforms and transcript variants not previously predicted from genome analysis...
  4. pmc The differentiation and stress response factor XBP-1 drives multiple myeloma pathogenesis
    Daniel R Carrasco
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, and Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cancer Cell 11:349-60. 2007
    ..The similarities of this model with the human disease, coupled with documented frequent XBP-1s overexpression in human MM, serve to implicate XBP-1s dysregulation in MM pathogenesis...
  5. ncbi request reprint The age of cancer
    R A DePinho
    Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 408:248-54. 2000
    ..Further verification of the role of these effects should in turn lead to the design of effective therapeutics for the treatment and prevention of cancer in the aged...
  6. ncbi request reprint What drives intense apoptosis resistance and propensity for necrosis in glioblastoma? A role for Bcl2L12 as a multifunctional cell death regulator
    Alexander H Stegh
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cell Cycle 7:2833-9. 2008
    ....
  7. pmc Ink4a/Arf tumor suppressor does not modulate the degenerative conditions or tumor spectrum of the telomerase-deficient mouse
    Christine M Khoo
    Department of Medical Oncology, Belfer Foundation Institute for Innovative Cancer Science, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:3931-6. 2007
    ..These observations highlight the importance of genetic context in dictating whether telomere dysfunction promotes or suppresses age-related degenerative conditions as well as the rate of initiation and type of spontaneous cancers...
  8. ncbi request reprint Up-regulation of c-Jun inhibits proliferation and induces apoptosis via caspase-triggered c-Abl cleavage in human multiple myeloma
    Klaus Podar
    Jerome Lipper Multiple Myeloma Center, Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Cancer Res 67:1680-8. 2007
    ..Finally, our data suggest that this mechanism may not only be restricted to MM but may also be important in a broad range of malignancies including erythroleukemia and solid tumors...
  9. ncbi request reprint Telomeres and the DNA damage response: why the fox is guarding the henhouse
    Richard S Maser
    Department of Medical Oncology, Dana Farber Cancer Institute, Departments of Medicine and Genetics, Harvard Medical School, Boston, MA 02115, USA
    DNA Repair (Amst) 3:979-88. 2004
    ..Here, we review recent work defining the roles for DSB repair machinery in telomere maintenance and in response to telomere dysfunction...
  10. ncbi request reprint Take care of your chromosomes lest cancer take care of you
    Richard S Maser
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Cell 3:4-6. 2003
    ....
  11. pmc Bcl2L12 inhibits post-mitochondrial apoptosis signaling in glioblastoma
    Alexander H Stegh
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Genes Dev 21:98-111. 2007
    ..Thus, Bcl2L12 contributes to the classical tumor biological features of GBM such as intense apoptosis resistance and florid necrosis, and may provide a target for enhanced therapeutic responsiveness of this lethal cancer...
  12. pmc Telomerase extracurricular activities
    Sandy Chang
    Department of Medical Oncology, Dana Farber Cancer Institute, Departments of Medicine and Genetics, Harvard Medical School, and Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:12520-2. 2002
  13. pmc PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas
    Hongwu Zheng
    Belfer Institute for Applied Cancer Science, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Cancer Cell 17:497-509. 2010
    ..The identification of PLAGL2 as a glioma oncogene highlights the importance of a growing class of cancer genes functioning to impart stem cell-like characteristics in malignant cells...
  14. ncbi request reprint Connecting chromosomes, crisis, and cancer
    Richard S Maser
    Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, M413, Boston, MA 02115, USA
    Science 297:565-9. 2002
    ..A greater understanding of telomere-induced crisis and the cell's crisis management mechanisms should guide the rational development of new therapeutics for cancer and other disorders...
  15. pmc Genetic analysis of Pten and Ink4a/Arf interactions in the suppression of tumorigenesis in mice
    Mingjian James You
    Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:1455-60. 2002
    ..This study provides genetic evidence of collaboration between Pten and Ink4a/Arf in constraining the growth and oncogenic transformation of cultured cells and in suppressing a wide spectrum of tumors in vivo...
  16. ncbi request reprint p53: good cop/bad cop
    Norman E Sharpless
    Department of Adult Oncology, Dana Farber Cancer Institute, Department of Medicine and Genetics, Harvard Medical School, Boston, MA 02115, USA
    Cell 110:9-12. 2002
    ..By extension, this relationship implies that therapies aimed to reduce cancer and postpone aging, and thereby increase longevity, will necessarily work either upstream or downstream, but not on the level of, p53...
  17. pmc Bcl2L12-mediated inhibition of effector caspase-3 and caspase-7 via distinct mechanisms in glioblastoma
    Alexander H Stegh
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:10703-8. 2008
    ..Thus, alphaB-crystallin is a Bcl2L12-induced oncoprotein that enables Bcl2L12 to block the activation of both effector caspases via distinct mechanisms, thereby contributing to GBM pathogenesis and its hallmark biological properties...
  18. pmc Obligate roles for p16(Ink4a) and p19(Arf)-p53 in the suppression of murine pancreatic neoplasia
    Nabeel Bardeesy
    Department of Adult Oncology, Dana Farber Cancer Institute, National Cancer Institute, Bethesda, Maryland, USA
    Mol Cell Biol 22:635-43. 2002
    ..This genetically defined model provides insights into the molecular pathogenesis of SCA and serves as a platform for dissection of cell-specific programs of epithelial tumor suppression...
  19. pmc mTORC1-dependent and -independent regulation of stem cell renewal, differentiation, and mobilization
    Boyi Gan
    Department of Medical Oncology, Belfer Foundation Institute for Innovative Cancer Science, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:19384-9. 2008
    ..Thus, TSC1 is a critical regulator of HSC self-renewal, mobilization, and multilineage development and executes these actions via both mTORC1-dependent and -independent pathways...
  20. ncbi request reprint Telomere dysfunction provokes regional amplification and deletion in cancer genomes
    Rónán C O'Hagan
    Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Cell 2:149-55. 2002
    ..This model provides a platform for discovery of genes responsible for the major cancers affecting aged humans...
  21. ncbi request reprint Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing
    KWOK KIN WONG
    Department of Adult Oncology, Dana Farber Cancer Institute Boston, Massachusetts 02115, USA
    Nature 421:643-8. 2003
    ....
  22. ncbi request reprint Cooperative interactions of p53 mutation, telomere dysfunction, and chronic liver damage in hepatocellular carcinoma progression
    Paraskevi A Farazi
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Res 66:4766-73. 2006
    ..Thus, this study supports a model that, in the face of chronic liver damage, attenuated p53 function and telomere-induced chromosomal instability play critical and cooperative roles in the progression of hepatocellular carcinoma...
  23. pmc Linking functional decline of telomeres, mitochondria and stem cells during ageing
    Ergun Sahin
    Belfer Institute for Applied Cancer Science, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 464:520-8. 2010
    ....
  24. pmc Constitutive telomerase expression promotes mammary carcinomas in aging mice
    Steven E Artandi
    Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street M413, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:8191-6. 2002
    ..These data indicate that enforced mTERT expression can promote the development of spontaneous cancers even in the setting of ample telomere reserve...
  25. pmc FoxOs are lineage-restricted redundant tumor suppressors and regulate endothelial cell homeostasis
    Ji Hye Paik
    Department of Medical Oncology, Dana Farber Cancer Institute, Brigham and Women s Hospital, and Harvard Medical School, Boston, MA 02115, USA
    Cell 128:309-23. 2007
    ..Functional studies validated Sprouty2 and PBX1, among others, as FoxO-regulated mediators of endothelial cell morphogenesis and vascular homeostasis...
  26. ncbi request reprint FoxOs are critical mediators of hematopoietic stem cell resistance to physiologic oxidative stress
    Zuzana Tothova
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Cell 128:325-39. 2007
    ..Thus, FoxO proteins play essential roles in the response to physiologic oxidative stress and thereby mediate quiescence and enhanced survival in the HSC compartment, a function that is required for its long-term regenerative potential...
  27. ncbi request reprint Impaired processing of DNA photoproducts and ultraviolet hypermutability with loss of p16INK4a or p19ARF
    Papri Sarkar-Agrawal
    Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA
    J Natl Cancer Inst 96:1790-3. 2004
    ..These results may further explain why INK4a/ARF mutations predispose to malignant melanoma, a UV-induced tumor...
  28. ncbi request reprint How disruption of cell cycle regulating genes might predispose to sun-induced skin cancer
    Thomas M Rünger
    Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    Cell Cycle 4:643-5. 2005
    ..Differences in the apoptotic response to ultraviolet light between melanocytes and keratinocytes might explain why INK4a/ARF mutations predispose to malignant melanoma, but not to keratinocyte-derived skin cancers...
  29. pmc mSin3-associated protein, mSds3, is essential for pericentric heterochromatin formation and chromosome segregation in mammalian cells
    Gregory David
    Departments of Medical Oncology, Medicine, and Genetics, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 17:2396-405. 2003
    ....
  30. pmc Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma
    Keith L Ligon
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Neuron 53:503-17. 2007
    ..Our findings identify an Olig2-regulated lineage-restricted pathway critical for proliferation of normal and tumorigenic CNS stem cells...
  31. pmc Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy
    Masayuki Nitta
    Department of Radiation Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, United States of America
    PLoS ONE 5:e10767. 2010
    ..These observations suggest that oxidative stress secondary to EGFR hyper-activation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design...
  32. pmc Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer
    Nabeel Bardeesy
    Massachusetts General Hospital Cancer Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 20:3130-46. 2006
    ....
  33. ncbi request reprint A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma
    Fenghua Liu
    Department of Neurological Surgery, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Cancer Res 66:10815-23. 2006
    ..This novel genome-wide approach greatly expanded the list of target genes in glioblastoma and represents a powerful new strategy to identify the upstream determinants of tumor phenotype in a range of human cancers...
  34. ncbi request reprint Marked genomic differences characterize primary and secondary glioblastoma subtypes and identify two distinct molecular and clinical secondary glioblastoma entities
    Elizabeth A Maher
    Center for Neuro Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Cancer Res 66:11502-13. 2006
    ..We conclude that glioblastoma is composed of at least three distinct molecular subtypes, including novel subgroups of secondary glioblastoma, which may benefit from different therapeutic strategies...
  35. pmc Pancreatic LKB1 deletion leads to acinar polarity defects and cystic neoplasms
    Aram F Hezel
    MGH Cancer Center, Simches Research Building, CPZN 4216, 185 Cambridge St, Boston, MA 02114, USA
    Mol Cell Biol 28:2414-25. 2008
    ..These genetic studies provide in vivo evidence of a key role for LKB1 in the establishment of epithelial cell polarity that is vital for pancreatic acinar cell function and viability and for the suppression of neoplasia...
  36. pmc mTORC1 signaling governs hematopoietic stem cell quiescence
    Boyi Gan
    Department of Medical Oncology, Dana Farber Cancer Institute and Department of Medicine and Genetics, Harvard Medical School, Boston, Massachusetts, USA
    Cell Cycle 8:1003-6. 2009
    ..Further pharmacological approaches show that PTEN, TSC1 and PML regulate HSC maintenance through mTORC1. mTORC1-mediated cell growth regulatory circuits thus play a critical role in the regulation of HSC quiescence...
  37. pmc Genomic alterations link Rho family of GTPases to the highly invasive phenotype of pancreas cancer
    Alec C Kimmelman
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:19372-7. 2008
    ..Like RIOK3, PAK4 promotes pancreas ductal cell motility and invasion. Together, the genomic and functional profiles establish the Rho family GTP-binding proteins as integral to the hallmark invasive nature of this lethal disease...
  38. doi request reprint Telomere dysfunction promotes genome instability and metastatic potential in a K-ras p53 mouse model of lung cancer
    Samanthi A Perera
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Carcinogenesis 29:747-53. 2008
    ..Furthermore, these findings clearly demonstrate (in an in vivo model system) the dual nature of telomere shortening as both a tumor-suppressive and tumor-promoting mechanism in lung cancer, dependent on p53 status...
  39. pmc Identification of a PTEN-regulated STAT3 brain tumor suppressor pathway
    Nuria de la Iglesia
    Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 22:449-62. 2008
    ..These findings indicate that STAT3 plays opposing roles in glial transformation depending on the genetic background of the tumor, providing the rationale for tailored therapeutic intervention in glioblastoma...
  40. pmc Glioma oncoprotein Bcl2L12 inhibits the p53 tumor suppressor
    Alexander H Stegh
    Belfer Institute for Applied Cancer Science, Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Genes Dev 24:2194-204. 2010
    ..Thus, Bcl2L12 is a multifunctional protein that contributes to intense therapeutic resistance of GBM through its ability to operate on two key nodes of cytoplasmic and nuclear signaling cascades...
  41. pmc Alu elements mediate MYB gene tandem duplication in human T-ALL
    Jennifer O'Neil
    Department of Pediatric Oncology, Belfer Foundation Institute for Innovative Cancer Science, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Exp Med 204:3059-66. 2007
    ..We conclude that Alu-mediated MYB tandem duplication occurs at low frequency during normal thymocyte development and is clonally selected during the molecular pathogenesis of human T-ALL...
  42. ncbi request reprint Common and distinct genomic events in sporadic colorectal cancer and diverse cancer types
    Eric S Martin
    Department of Medical Oncology, Belfer Institute for Innovative Cancer Science, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 67:10736-43. 2007
    ....
  43. ncbi request reprint Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies
    Jayne M Stommel
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
    Science 318:287-90. 2007
    ..Thus, effective GBM therapy may require combined regimens targeting multiple RTKs...
  44. pmc p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation
    Hongwu Zheng
    Department of Medical Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 455:1129-33. 2008
    ....
  45. pmc High-resolution genomic profiles of human lung cancer
    Giovanni Tonon
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:9625-30. 2005
    ..Integrated DNA-RNA analyses identified WHSC1L1 and TPX2 as two candidates likely targeted for amplification in both pancreatic ductal adenocarcinoma and non-small-cell lung cancer...
  46. ncbi request reprint Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a
    Diego H Castrillon
    Department of Medical Oncology, Dana Farber Cancer Institute, and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
    Science 301:215-8. 2003
    ....
  47. ncbi request reprint LKB1 (XEEK1) regulates Wnt signalling in vertebrate development
    Olga Ossipova
    Department of Cancer Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Nat Cell Biol 5:889-94. 2003
    ..These studies show that LKB1/XEEK1 is required for Wnt-beta-catenin signalling in frogs and mammals and provides novel insights into its role in vertebrate developmental patterning and carcinogenesis...
  48. ncbi request reprint The age of cancer: telomeres, checkpoints, and longevity
    Ronald A Depinho
    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Clin Invest 111:S9-14. 2003
  49. pmc Telomere-based crisis: functional differences between telomerase activation and ALT in tumor progression
    Sandy Chang
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Genes Dev 17:88-100. 2003
    ....
  50. ncbi request reprint Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation
    Nabeel Bardeesy
    Department of Adult Oncology, Dana Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 419:162-7. 2002
    ..Together, our data rationalize several features of PJS polyposis--notably its peculiar histopathological presentation and limited malignant potential--and place Lkb1 in a distinct class of tumour suppressors...
  51. ncbi request reprint A genetic screen for candidate tumor suppressors identifies REST
    Thomas F Westbrook
    Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Cell 121:837-48. 2005
    ..These results implicate REST as a human tumor suppressor and provide a novel approach to identifying candidate genes that suppress the development of human cancer...
  52. pmc Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation
    Xiaocheng C Dong
    Howard Hughes Medical Institute, Division of Endocrinology, Children s Hospital Boston, Karp Family Research Laboratories, 300 Longwood Avenue, Harvard Medical School, Boston, MA 02115, USA
    Cell Metab 8:65-76. 2008
    ....
  53. ncbi request reprint Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis
    Robert M Bachoo
    Center for Neuro Oncology, Boston, Massachusetts 02115, USA
    Cancer Cell 1:269-77. 2002
    ..These data support the view that dysregulation of specific genetic pathways, rather than cell-of-origin, dictates the emergence and phenotype of high-grade gliomas...
  54. pmc The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress
    Reuben J Shaw
    Department of Systems Biology, Harvard Medical School, and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Proc Natl Acad Sci U S A 101:3329-35. 2004
    ..The role of LKB1/AMPK in the survival of a subset of genetically defined tumor cells may provide opportunities for cancer therapeutics...
  55. pmc Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma
    Andrew J Aguirre
    Department of Medical Oncology, Dana Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
    Genes Dev 17:3112-26. 2003
    ..This faithful mouse model may permit the systematic analysis of genetic lesions implicated in the human disease and serve as a platform for the identification of early disease markers and for the efficient testing of novel therapies...
  56. pmc p16(Ink4a) interferes with Abelson virus transformation by enhancing apoptosis
    Zohar Sachs
    Department of Pathology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Virol 78:3304-11. 2004
    ..These results indicate that both products of the Ink4a/Arf locus influence Ab-MLV transformation and reveal that in addition to its well-recognized effects on the cell cycle, p16(Ink4a) can suppress transformation by inducing apoptosis...
  57. ncbi request reprint Differential impact of telomere dysfunction on initiation and progression of hepatocellular carcinoma
    Paraskevi A Farazi
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 63:5021-7. 2003
    ....
  58. pmc Molecular diversity of astrocytes with implications for neurological disorders
    Robert M Bachoo
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:8384-9. 2004
    ....
  59. ncbi request reprint Stromal biology of pancreatic cancer
    Gerald C Chu
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA
    J Cell Biochem 101:887-907. 2007
    ..Such knowledge may be used to understand the evolution and biology of this lethal cancer and may convert these insights into new points of therapeutic intervention...
  60. pmc FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis
    Ji Hye Paik
    Department of Medical Oncology, Belfer Institute for Applied Cancer Science, Harvard Medical School, Boston, MA 02115, USA
    Cell Stem Cell 5:540-53. 2009
    ..Thus, the FoxO family coordinately regulates diverse genes and pathways to govern key aspects of NSC homeostasis in the mammalian brain...
  61. pmc DNA-dependent protein kinase catalytic subunit is not required for dysfunctional telomere fusion and checkpoint response in the telomerase-deficient mouse
    Richard S Maser
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Mol Cell Biol 27:2253-65. 2007
    ....
  62. pmc PI3 kinase signals BCR-dependent mature B cell survival
    Lakshmi Srinivasan
    Program of Cellular and Molecular Medicine, Children s Hospital, and Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA
    Cell 139:573-86. 2009
    ....
  63. ncbi request reprint Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a
    Viktor Janzen
    Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Nature 443:421-6. 2006
    ..Inhibition of p16INK4a may ameliorate the physiological impact of ageing on stem cells and thereby improve injury repair in aged tissue...
  64. pmc Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse
    Nabeel Bardeesy
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:5947-52. 2006
    ....
  65. ncbi request reprint High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients
    Daniel R Carrasco
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Cancer Cell 9:313-25. 2006
    ....
  66. ncbi request reprint STAT3 is a negative regulator of granulopoiesis but is not required for G-CSF-dependent differentiation
    Chien Kuo Lee
    Department of Pathology, Kaplan Comprehensive Cancer Center, New York University School of Medicine, 10016, USA
    Immunity 17:63-72. 2002
    ....
  67. ncbi request reprint Walking the telomere plank into cancer
    KWOK KIN WONG
    J Natl Cancer Inst 95:1184-6. 2003
  68. ncbi request reprint Keeping telomerase in its place
    Richard S Maser
    Nat Med 8:934-6. 2002
  69. doi request reprint LKB1 signaling in mesenchymal cells required for suppression of gastrointestinal polyposis
    Pekka Katajisto
    Genome Scale Biology Program and Institute of Biomedicine, Biomedicum Helsinki, 00014 University of Helsinki, Finland
    Nat Genet 40:455-9. 2008
    ..We also noted TGFbeta signaling defects in polyps of individuals with PJS, suggesting that the identified stromal-derived mechanism of tumor suppression is also relevant in PJS...
  70. ncbi request reprint The role of Ink4a/Arf in ErbB2 mammary gland tumorigenesis
    Mark D'Amico
    Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, D C 20007, USA
    Cancer Res 63:3395-402. 2003
    ..In view of the important role of Ink4a/Arf in response to chemotherapy, these transgenic mice may provide a useful model for testing breast tumor therapies...
  71. ncbi request reprint Cancer chromosomes in crisis
    Ronald A Depinho
    Nat Genet 36:932-4. 2004
    ....
  72. ncbi request reprint Block of T cell development in P53-deficient mice accelerates development of lymphomas with characteristic RAG-dependent cytogenetic alterations
    Brian B Haines
    Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Cancer Cell 9:109-20. 2006
    ..These findings provide genetic evidence that block of lymphocyte development at stages with RAG endonuclease activity can provoke lymphomagenesis on a background with deficient DNA damage responses...
  73. ncbi request reprint Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects
    David A Tuveson
    Abramson Family Cancer Research Institute, Abramson Cancer Center and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104 USA
    Cancer Cell 5:375-87. 2004
    ..Our results suggest that endogenous oncogenic ras is sufficient to initiate transformation by stimulating proliferation, while further genetic lesions may be necessary for progression to frank malignancy...
  74. ncbi request reprint The differential impact of p16(INK4a) or p19(ARF) deficiency on cell growth and tumorigenesis
    Norman E Sharpless
    Department of Medicine, Lineberger Cancer Center, CB 7295, The University of North Carolina School of Medicine, Chapel Hill, NC 27599 7295, USA
    Oncogene 23:379-85. 2004
    ....
  75. ncbi request reprint Absence of telomerase and shortened telomeres have minimal effects on skin and pancreatic carcinogenesis elicited by viral oncogenes
    David Argilla
    Department of Biochemistry and Biophysics, Diabetes Center, and Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA
    Cancer Cell 6:373-85. 2004
    ....
  76. ncbi request reprint Direct transcriptional activation of promyelocytic leukemia protein by IFN regulatory factor 3 induces the p53-dependent growth inhibition of cancer cells
    Tae Kyung Kim
    The Laboratory of Cell Growth and Function Regulation, Division of Biotechnology, College of Life Sciences and Biotechnology, School of Medicine, Korea University, Anam Dong, Seongbuk gu, Seoul 136 713, South Korea
    Cancer Res 67:11133-40. 2007
    ....
  77. pmc Telomeres, stem cells, senescence, and cancer
    Norman E Sharpless
    Department of Medicine and Genetics, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 8212, USA
    J Clin Invest 113:160-8. 2004
    ..g., p16(INK4a)-Rb, ARF-p53, and the telomere) have evolved to ward against this possibility. These beneficial antitumor pathways, however, appear also to limit the stem cell life span, thereby contributing to aging...
  78. pmc A Foxo/Notch pathway controls myogenic differentiation and fiber type specification
    Tadahiro Kitamura
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA
    J Clin Invest 117:2477-85. 2007
    ..Notch/Foxo1 cooperation may integrate environmental cues through Notch with metabolic cues through Foxo1 to regulate progenitor cell maintenance and differentiation...
  79. pmc Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway
    Purnima R Laud
    Department of Molecular Genetics, University of Texas, The M D Anderson Cancer Center, Houston, Texas 77030, USA
    Genes Dev 19:2560-70. 2005
    ....
  80. ncbi request reprint Cancer: crime and punishment
    Norman E Sharpless
    Nature 436:636-7. 2005
  81. ncbi request reprint Ink4a/arf deficiency promotes ultraviolet radiation-induced melanomagenesis
    Juan A Recio
    Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892 4264, USA
    Cancer Res 62:6724-30. 2002
    ....
  82. pmc Cellular transformation by the MSP58 oncogene is inhibited by its physical interaction with the PTEN tumor suppressor
    Koichi Okumura
    Ludwig Institute for Cancer Research, San Diego Branch, University of California at San Diego, La Jolla, CA 92093 0660, USA
    Proc Natl Acad Sci U S A 102:2703-6. 2005
    ....
  83. ncbi request reprint Genome-wide retroviral insertional tagging of genes involved in cancer in Cdkn2a-deficient mice
    Anders H Lund
    Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
    Nat Genet 32:160-5. 2002
    ....
  84. ncbi request reprint Cancer biology: gone but not forgotten
    Norman E Sharpless
    Nature 445:606-7. 2007
  85. ncbi request reprint Decreased cyclin-dependent kinase 5 (cdk5) activity is accompanied by redistribution of cdk5 and cytoskeletal proteins and increased cytoskeletal protein phosphorylation in p35 null mice
    Janice L Hallows
    The Nathan Shock Center of Excellence in the Basic Biology of Aging and Department of Pathology, University of Washington, Seattle, Washington 98195, USA
    J Neurosci 23:10633-44. 2003
    ..Our studies illustrate that p35 regulates the subcellular distribution of cdk5 and cytoskeletal proteins in neurons and that cdk5 has a hierarchical role in regulating the phosphorylation and function of cytoskeletal proteins...
  86. ncbi request reprint Essential role of limiting telomeres in the pathogenesis of Werner syndrome
    Sandy Chang
    Department of Molecular Genetics, M D Anderson Cancer Center, Box 11, 1515 Holcombe Blvd, Houston, Texas 77030, USA
    Nat Genet 36:877-82. 2004
    ..These genetic data indicate that the delayed manifestation of the complex pleiotropic of Wrn deficiency relates to telomere shortening...
  87. pmc Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling
    Hye Min Jeon
    School of Life Sciences and Biotechnology, Korea University, Seoul 136 713, Republic of Korea
    Genes Dev 22:2028-33. 2008
    ..Thus, Id4 plays an integral role in the transformation of astrocytes via its combined actions on two-key cell cycle and differentiation regulatory molecules...
  88. doi request reprint SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway
    Sebastian Herzog
    Max Planck Institute for Immunobiology, 79108 Freiburg, Germany
    Nat Immunol 9:623-31. 2008
    ..Together, these data illuminate a molecular function of SLP-65 and identify a key role for Foxo proteins in the regulation of light chain recombination, receptor editing and B cell selection...
  89. pmc Specific requirement of the chromatin modifier mSin3B in cell cycle exit and cellular differentiation
    Gregory David
    Department of Pharmacology and New York University Cancer Institute, New York University School of Medicine, New York, NY 10016, USA
    Proc Natl Acad Sci U S A 105:4168-72. 2008
    ....
  90. ncbi request reprint p16(Ink4a) in melanocyte senescence and differentiation
    Elena V Sviderskaya
    Department of Anatomy and Developmental Biology, St George s Hospital Medical School, Cranmer Terrace, London SW17 0RE, U K
    J Natl Cancer Inst 94:446-54. 2002
    ..Because senescence is believed to be an anticancer mechanism, we investigated the role of Ink4a-Arf and its individual components in melanocyte senescence...

Research Grants23

  1. TELOMERASE IN DEVELOPMENT, SENESCENCE AND NEOPLASIA
    Ronald DePinho; Fiscal Year: 2007
    ....
  2. Genetics and Biology of Pancreatic Duct Adenocarcinoma
    Ronald DePinho; Fiscal Year: 2007
    ....
  3. Evolution of Primary and Resistant Solid Tumors
    Ronald DePinho; Fiscal Year: 2007
    ..Finally, nanosensors will be developed that are capable to detecting telomerase activity and quantifying telomere reserves. ..
  4. TELOMERASE IN DEVELOPMENT, SENESCENCE AND NEOPLASIA
    Ronald DePinho; Fiscal Year: 2009
    ....
  5. Genetics and Biology of Malignant Glioma
    Ronald DePinho; Fiscal Year: 2007
    ..The goals of this P01 mirror precisely the priorities articulated by the recent NCI/NINDS Brain Tumor PRG. ..
  6. TELOMERASE IN DEVELOPMENT, SENESCENCE AND NEOPLASIA
    Ronald DePinho; Fiscal Year: 2006
    ....
  7. TELOMERASE IN DEVELOPMENT, SENESCENCE AND NEOPLASIA
    Ronald DePinho; Fiscal Year: 2005
    ....
  8. Conference on Mouse Models of Cancer
    Ronald DePinho; Fiscal Year: 2003
    ..Such systems hold significant promise in accelerating and making more accurate the evaluation of these compounds prior to entry into the clinic. ..
  9. TELOMERASE IN DEVELOPMENT, SENESCENCE AND NEOPLASIA
    RONALD ANTHONY DEPINHO; Fiscal Year: 2010
    ..We will validate the principal of telomerase extinction as an anti-cancer therapy and define potential resistance mechanisms which should lead to new drugs that may synergize with anti-telomerase therapy. ..