William G. Kaelin Jr., MD

William G. Kaelin Jr., MD

Researcher

Contact Information

Office Phone Number

617-632-3975

Fax

617-632-4760

Biography

William G. Kaelin Jr., MD

William G. Kaelin, Jr., MD, is the 2019 Nobel Prize recipient in medicine or physiology. Dr. Kaelin received his MD from Duke University in 1982 and was a house officer and chief resident in internal medicine at Johns Hopkins Hospital. He was a medical oncology clinical fellow at Dana-Farber and a postdoctoral fellow in the laboratory of Dr. David Livingston, where he began his studies of tumor suppressor proteins. He became an independent investigator at Dana-Farber in 1992, and a Howard Hughes Medical Institute Investigator and Professor of Medicine at Harvard Medical School in 2002. The 2019 Nobel was awarded jointly to Kaelin, Sir Peter J. Ratcliffe and Gregg L. Semenza for their discoveries of how cells sense and adapt to oxygen availability.

Researcher

Physician

Sidney Farber Professor of Medicine, Harvard Medical School
Investigator, Howard Hughes Medical Institute

Recent Awards

  • Nobel Prize in Medicine or Physiology, 2019
  • Lasker Award for Basic Medical Research, Albert and Mary Lasker Foundation, 2016
  • Science of Oncology Award, ASCO

    2016

  • The Princess Takamatsu Award, AACR

    2016

  • Wiley Prize in Biomedical Sciences

    2014

  • AACR Academy

    2014

  • Steven C. Beering Award

    2014

  • Scientific Grand Prix, Foundation Lefoulon-Delalande

    2012

  • Stanley J. Korsmeyer Award, ASCI

    2012

  • Alfred Knudson Award in Cancer Genetics, NCI

    2011

  • Canada Gairdner International Award

    2010

  • Elected to National Academy of Sciences

    2010

  • AICR Colin Thomson Medal

    2008

  • Elected to Institute of Medicine

    2007

  • Duke University School of Medicine Distinguished Alumni Award

    2007

  • Doris Duke Distinguished Clinical Investigator Award

    2006

  • Richard and Hinda Rosenthal Foundation Award, AACR

    2006

  • Elected to Johns Hopkins Society of Scholars

    2003

  • Paul Marks Prize, Memorial Sloan Kettering Cancer Center

    2001

  • James S. McDonnell Scholar Award

    1993

  • NIH Physician-Scientist Award

    1990

  • NIH National Research Service Award

    1990

  • Alpha Omega Alpha Medical Honor Society

    1983

  • Phi Beta Kappa

    1978

  • Jill Rose Award 2020

Research

    Functions of Tumor Suppressor Proteins

    Our laboratory studies tumor suppressor genes and the normal functions of the proteins they encode. The long-term goal of this work is to lay the foundation for the development of new anticancer therapies based on the functions of specific tumor suppressor proteins. For example, it may be possible to develop a drug that mimics the behavior of a certain tumor suppressor protein, or to design strategies for killing only those cells in which a particular tumor suppressor protein has been inactivated, thus sparing normal cells.We are currently concentrating on the von Hippel-Lindau tumor suppressor protein (pVHL), the retinoblastoma tumor suppressor protein (pRB), and the p53-like protein p73. pVHL inactivation is common in several cancers including clear cell renal carcinoma. Our laboratory established that when oxygen is available, pVHL targets for destruction another protein called hypoxia-inducible factor (HIF). Cells lacking pVHL, or starved of oxygen, accumulate HIF, which activates a cadre of genes that facilitate adaptation to hypoxia. We showed that downregulation of HIF is both necessary and sufficient for pVHL to suppress the growth of renal carcinomas in experimental models. This work motivated clinical trials of agents that inhibit HIF-responsive growth factors such as vascular endothelial growth factor (VEGF). At least one VEGF inhibitor will likely be approved for the treatment of renal carcinoma in 2005.Earlier work by our group showed that the binding of pVHL to HIF requires that HIF be hydroxylated on one of two proline residues. Preclinical data suggest that preventing this modification pharmacologically might be useful for the treatment of diseases characterized by impaired oxygen delivery, including myocardial infarctions and strokes. In other research, we are studying tuberous sclerosis, a hereditary cancer syndrome caused by mutations of either the TSC1 or TSC2 genes. We recently discovered that TSC1 and TSC2, like pVHL, regulate HIF; we also found that another protein, REDD1, plays an important role in adaptation to chronic hypoxia by modulating the function of TSC1 and TSC2. The best understood function of the pRB protein is its ability to inhibit the E2F transcription factor. We discovered that pRB interacts with another protein, RBP2, which also has features of a transcription factor. Importantly, we showed that inhibition of RBP2 in cells lacking pRB induces some of the same changes observed following restoration of pRB function, including the induction of differentiation. We are now studying the biochemistry of RBP2 in greater detail.

    Publications

      • The INDIGO Trial: Precision Medicine Finally Comes to Glioma. Neuro Oncol. 2023 Sep 12. View in: Pubmed

      • Prolonged hypoxia alleviates prolyl hydroxylation-mediated suppression of RIPK1 to promote necroptosis and inflammation. Nat Cell Biol. 2023 Jul; 25(7):950-962. View in: Pubmed

      • von-Hippel Lindau and Hypoxia-Inducible Factor at the Center of Renal Cell Carcinoma Biology. Hematol Oncol Clin North Am. 2023 10; 37(5):809-825. View in: Pubmed

      • Protocol to establish a genetically engineered mouse model of IDH1-mutant astrocytoma. STAR Protoc. 2023 May 06; 4(2):102281. View in: Pubmed

      • Isocitrate dehydrogenase (IDH) mutant gliomas: A Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions. Neuro Oncol. 2023 01 05; 25(1):4-25. View in: Pubmed

      • A Mesenchymal Tumor Cell State Confers Increased Dependency on the BCL-XL Antiapoptotic Protein in Kidney Cancer. Clin Cancer Res. 2022 11 01; 28(21):4689-4701. View in: Pubmed

      • Von Hippel-Lindau disease: insights into oxygen sensing, protein degradation, and cancer. J Clin Invest. 2022 09 15; 132(18). View in: Pubmed

      • De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma. Cancer Cell. 2022 09 12; 40(9):939-956.e16. View in: Pubmed

      • Mitochondrial remodeling and ischemic protection by G protein-coupled receptor 35 agonists. Science. 2022 08 05; 377(6606):621-629. View in: Pubmed

      • Sensitivity of VHL mutant kidney cancers to HIF2 inhibitors does not require an intact p53 pathway. Proc Natl Acad Sci U S A. 2022 04 05; 119(14):e2120403119. View in: Pubmed

      • From Basic Science to Clinical Translation in Kidney Cancer: A Report from the Second Kidney Cancer Research Summit. Clin Cancer Res. 2022 03 01; 28(5):831-839. View in: Pubmed

      • THE JEREMIAH METZGER LECTURE:VON HIPPEL-LINDAU DISEASE: INSIGHTS INTO OXYGEN SENSING, CANCER AND DRUGGING THE UNDRUGGABLE. Trans Am Clin Climatol Assoc. 2022; 132:170-181. View in: Pubmed

      • David M. Livingston (1941-2021). Cell. 2021 12 09; 184(25):6007-6009. View in: Pubmed

      • Belzutifan, a Potent HIF2a Inhibitor, in the Pacak-Zhuang Syndrome. N Engl J Med. 2021 11 25; 385(22):2059-2065. View in: Pubmed

      • Targeting oncoproteins with a positive selection assay for protein degraders. Sci Adv. 2021 02; 7(6). View in: Pubmed

      • Author Correction: Skp2 dictates cell cycle-dependent metabolic oscillation between glycolysis and TCA cycle. Cell Res. 2021 Jan; 31(1):104. View in: Pubmed

      • 2-Oxoglutarate-dependent dioxygenases in cancer. Nat Rev Cancer. 2020 12; 20(12):710-726. View in: Pubmed

      • Targeting the HIF2-VEGF axis in renal cell carcinoma. Nat Med. 2020 10; 26(10):1519-1530. View in: Pubmed

      • Skp2 dictates cell cycle-dependent metabolic oscillation between glycolysis and TCA cycle. Cell Res. 2021 01; 31(1):80-93. View in: Pubmed

      • CDK7 Inhibition Potentiates Genome Instability Triggering Anti-tumor Immunity in Small Cell Lung Cancer. Cancer Cell. 2020 01 13; 37(1):37-54.e9. View in: Pubmed

      • Leveraging insights into cancer metabolism-a symposium report. Ann N Y Acad Sci. 2020 02; 1462(1):5-13. View in: Pubmed

      • The KDM5A/RBP2 histone demethylase represses NOTCH signaling to sustain neuroendocrine differentiation and promote small cell lung cancer tumorigenesis. Genes Dev. 2019 12 01; 33(23-24):1718-1738. View in: Pubmed

      • HIF-independent synthetic lethality between CDK4/6 inhibition and VHL loss across species. Sci Signal. 2019 10 01; 12(601). View in: Pubmed

      • Mutant p53 induces a hypoxia transcriptional program in gastric and esophageal adenocarcinoma. JCI Insight. 2019 08 08; 4(15). View in: Pubmed

      • EglN3 hydroxylase stabilizes BIM-EL linking VHL type 2C mutations to pheochromocytoma pathogenesis and chemotherapy resistance. Proc Natl Acad Sci U S A. 2019 08 20; 116(34):16997-17006. View in: Pubmed

      • Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate. Science. 2019 03 15; 363(6432):1217-1222. View in: Pubmed

      • Deubiquitinases Maintain Protein Homeostasis and Survival of Cancer Cells upon Glutathione Depletion. Cell Metab. 2019 05 07; 29(5):1166-1181.e6. View in: Pubmed

      • Peptidic degron for IMiD-induced degradation of heterologous proteins. Proc Natl Acad Sci U S A. 2019 02 12; 116(7):2539-2544. View in: Pubmed

      • Cells Lacking the RB1 Tumor Suppressor Gene Are Hyperdependent on Aurora B Kinase for Survival. Cancer Discov. 2019 02; 9(2):230-247. View in: Pubmed

      • BRCA1-IRIS promotes human tumor progression through PTEN blockade and HIF-1a activation. Proc Natl Acad Sci U S A. 2018 10 09; 115(41):E9600-E9609. View in: Pubmed

      • Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma. Cell. 2018 09 20; 175(1):101-116.e25. View in: Pubmed

      • VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma. Science. 2018 07 20; 361(6399):290-295. View in: Pubmed

      • Autochthonous tumors driven by Rb1 loss have an ongoing requirement for the RBP2 histone demethylase. Proc Natl Acad Sci U S A. 2018 04 17; 115(16):E3741-E3748. View in: Pubmed

      • HIF2 Inhibitor Joins the Kidney Cancer Armamentarium. J Clin Oncol. 2018 03 20; 36(9):908-910. View in: Pubmed

      • Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science. 2018 Feb 16; 359(6377):801-806. View in: Pubmed

      • Senator McCain and Our Shared Humanity. Am J Med. 2018 03; 131(3):216-217. View in: Pubmed

      • Climate Change: What Would Lincoln Do? JAMA. 2017 Aug 15; 318(7):611. View in: Pubmed

      • HIF activation causes synthetic lethality between the VHL tumor suppressor and the EZH1 histone methyltransferase. Sci Transl Med. 2017 07 12; 9(398). View in: Pubmed

      • The EGLN-HIF O2-Sensing System: Multiple Inputs and Feedbacks. Mol Cell. 2017 Jun 15; 66(6):772-779. View in: Pubmed

      • Publish houses of brick, not mansions of straw. Nature. 2017 05 23; 545(7655):387. View in: Pubmed

      • Common pitfalls in preclinical cancer target validation. Nat Rev Cancer. 2017 07; 17(7):425-440. View in: Pubmed

      • Inactivation of the PBRM1 tumor suppressor gene amplifies the HIF-response in VHL-/- clear cell renal carcinoma. Proc Natl Acad Sci U S A. 2017 01 31; 114(5):1027-1032. View in: Pubmed

      • The VHL Tumor Suppressor Gene: Insights into Oxygen Sensing and Cancer. Trans Am Clin Climatol Assoc. 2017; 128:298-307. View in: Pubmed

      • Targeting HIF2 in Clear Cell Renal Cell Carcinoma. Cold Spring Harb Symp Quant Biol. 2016; 81:113-121. View in: Pubmed

      • Pathways for Oxygen Regulation and Homeostasis: The 2016 Albert Lasker Basic Medical Research Award. JAMA. 2016 Sep 27; 316(12):1252-3. View in: Pubmed

      • PHD3 Loss in Cancer Enables Metabolic Reliance on Fatty Acid Oxidation via Deactivation of ACC2. Mol Cell. 2016 09 15; 63(6):1006-20. View in: Pubmed

      • On-target efficacy of a HIF-2a antagonist in preclinical kidney cancer models. Nature. 2016 11 03; 539(7627):107-111. View in: Pubmed

      • pVHL suppresses kinase activity of Akt in a proline-hydroxylation-dependent manner. Science. 2016 08 26; 353(6302):929-32. View in: Pubmed

      • Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine. Cell. 2016 Jun 30; 166(1):126-39. View in: Pubmed

      • EGLN1 Inhibition and Rerouting of a-Ketoglutarate Suffice for Remote Ischemic Protection. Cell. 2016 Apr 07; 165(2):497. View in: Pubmed

      • EGLN1 Inhibition and Rerouting of a-Ketoglutarate Suffice for Remote Ischemic Protection. Cell. 2016 Feb 25; 164(5):884-95. View in: Pubmed

      • Fumarate and Succinate Regulate Expression of Hypoxia-inducible Genes via TET Enzymes. J Biol Chem. 2016 Feb 19; 291(8):4256-65. View in: Pubmed

      • Peptidic degron in EID1 is recognized by an SCF E3 ligase complex containing the orphan F-box protein FBXO21. Proc Natl Acad Sci U S A. 2015 Dec 15; 112(50):15372-7. View in: Pubmed

      • Treatment Response Assessment in IDH-Mutant Glioma Patients by Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate. Clin Cancer Res. 2016 Apr 01; 22(7):1632-41. View in: Pubmed

      • EglN2 associates with the NRF1-PGC1a complex and controls mitochondrial function in breast cancer. EMBO J. 2015 Dec 02; 34(23):2953-70. View in: Pubmed

      • Inhibition of the oxygen sensor PHD2 in the liver improves survival in lactic acidosis by activating the Cori cycle. Proc Natl Acad Sci U S A. 2015 Sep 15; 112(37):11642-7. View in: Pubmed

      • DisABLing kidney cancers caused by fumarate hydratase mutations. Cancer Cell. 2014 Dec 08; 26(6):779-780. View in: Pubmed

      • Genetic evidence of a precisely tuned dysregulation in the hypoxia signaling pathway during oncogenesis. Cancer Res. 2014 Nov 15; 74(22):6554-64. View in: Pubmed

      • A genetic mechanism for Tibetan high-altitude adaptation. Nat Genet. 2014 Sep; 46(9):951-6. View in: Pubmed

      • Phosphorylation of ETS1 by Src family kinases prevents its recognition by the COP1 tumor suppressor. Cancer Cell. 2014 Aug 11; 26(2):222-34. View in: Pubmed

      • Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase. Genes Dev. 2014 Jul 01; 28(13):1429-44. View in: Pubmed

      • A phase I study of cabozantinib (XL184) in patients with renal cell cancer. Ann Oncol. 2014 Aug; 25(8):1603-8. View in: Pubmed

      • D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice. Genes Dev. 2014 Mar 01; 28(5):479-90. View in: Pubmed

      • SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer. Cancer Cell. 2013 Dec 09; 24(6):738-50. View in: Pubmed

      • The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science. 2014 Jan 17; 343(6168):305-9. View in: Pubmed

      • Twenty-fifth annual Pezcoller Symposium: Metabolism and tumorigenesis. Cancer Res. 2013 Oct 15; 73(20):6124-7. View in: Pubmed

      • Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature. 2013 Jul 04; 499(7456):43-9. View in: Pubmed

      • What a difference a hydroxyl makes: mutant IDH, (R)-2-hydroxyglutarate, and cancer. Genes Dev. 2013 Apr 15; 27(8):836-52. View in: Pubmed

      • Influence of metabolism on epigenetics and disease. Cell. 2013 Mar 28; 153(1):56-69. View in: Pubmed

      • (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science. 2013 Mar 29; 339(6127):1621-5. View in: Pubmed

      • Coordinated repression of cell cycle genes by KDM5A and E2F4 during differentiation. Proc Natl Acad Sci U S A. 2012 Nov 06; 109(45):18499-504. View in: Pubmed

      • Molecular biology. Use and abuse of RNAi to study mammalian gene function. Science. 2012 Jul 27; 337(6093):421-2. View in: Pubmed

      • The VHL/HIF axis in clear cell renal carcinoma. Semin Cancer Biol. 2013 Feb; 23(1):18-25. View in: Pubmed

      • Treatment of erythropoietin deficiency in mice with systemically administered siRNA. Blood. 2012 Aug 30; 120(9):1916-22. View in: Pubmed

      • Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature. 2012 Feb 15; 483(7390):484-8. View in: Pubmed

      • Cancer and altered metabolism: potential importance of hypoxia-inducible factor and 2-oxoglutarate-dependent dioxygenases. Cold Spring Harb Symp Quant Biol. 2011; 76:335-45. View in: Pubmed

      • Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A-TCF7L2 fusion. Nat Genet. 2011 Sep 04; 43(10):964-968. View in: Pubmed

      • New insights into the biology of renal cell carcinoma. Hematol Oncol Clin North Am. 2011 Aug; 25(4):667-86. View in: Pubmed

      • Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1. Proc Natl Acad Sci U S A. 2011 Aug 16; 108(33):13379-86. View in: Pubmed

      • Genetic and functional studies implicate HIF1a as a 14q kidney cancer suppressor gene. Cancer Discov. 2011 Aug; 1(3):222-35. View in: Pubmed

      • Clinical and functional properties of novel VHL mutation (X214L) consistent with Type 2A phenotype and low risk of renal cell carcinoma. Clin Genet. 2011 Jun; 79(6):539-45. View in: Pubmed

      • Good COP1 or bad COP1? In vivo veritas. J Clin Invest. 2011 Apr; 121(4):1263-5. View in: Pubmed

      • Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility. Endocr Relat Cancer. 2011 Feb; 18(1):73-83. View in: Pubmed

      • FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis. Cancer Cell. 2010 Nov 16; 18(5):472-84. View in: Pubmed

      • New cancer targets emerging from studies of the Von Hippel-Lindau tumor suppressor protein. Ann N Y Acad Sci. 2010 Oct; 1210:1-7. View in: Pubmed

      • Loss of hypoxia-inducible factor prolyl hydroxylase activity in cardiomyocytes phenocopies ischemic cardiomyopathy. Circulation. 2010 Sep 07; 122(10):1004-16. View in: Pubmed

      • Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase. Cancer Cell. 2010 Aug 09; 18(2):147-59. View in: Pubmed

      • Reactivation of hepatic EPO synthesis in mice after PHD loss. Science. 2010 Jul 23; 329(5990):407. View in: Pubmed

      • Erlotinib therapy for central nervous system hemangioblastomatosis associated with von Hippel-Lindau disease: a case report. J Neurooncol. 2011 Jan; 101(2):307-10. View in: Pubmed

      • Q&A: Cancer: clues from cell metabolism. Nature. 2010 Jun 03; 465(7298):562-4. View in: Pubmed

      • Prostate cancer: beta control your hormones. Cancer Cell. 2010 Apr 13; 17(4):311-2. View in: Pubmed

      • Slaying RAS with a synthetic lethal weapon. Cell Res. 2010 Feb; 20(2):119-21. View in: Pubmed

      • Control of cyclin D1 and breast tumorigenesis by the EglN2 prolyl hydroxylase. Cancer Cell. 2009 Nov 06; 16(5):413-24. View in: Pubmed

      • Synthetic lethality: a framework for the development of wiser cancer therapeutics. Genome Med. 2009 Oct 27; 1(10):99. View in: Pubmed

      • SDH5 mutations and familial paraganglioma: somewhere Warburg is smiling. Cancer Cell. 2009 Sep 08; 16(3):180-2. View in: Pubmed

      • A feedback loop involving the Phd3 prolyl hydroxylase tunes the mammalian hypoxic response in vivo. Mol Cell Biol. 2009 Nov; 29(21):5729-41. View in: Pubmed

      • HIF2alpha cooperates with RAS to promote lung tumorigenesis in mice. J Clin Invest. 2009 Aug; 119(8):2160-70. View in: Pubmed

      • Patterns of gene expression and copy-number alterations in von-hippel lindau disease-associated and sporadic clear cell carcinoma of the kidney. Cancer Res. 2009 Jun 01; 69(11):4674-81. View in: Pubmed

      • Treatment of kidney cancer: insights provided by the VHL tumor-suppressor protein. Cancer. 2009 May 15; 115(10 Suppl):2262-72. View in: Pubmed

      • Innovations and challenges in renal cancer: summary statement from the Third Cambridge Conference. Cancer. 2009 May 15; 115(10 Suppl):2247-51. View in: Pubmed

      • Kidney cancer: now available in a new flavor. Cancer Cell. 2008 Dec 09; 14(6):423-4. View in: Pubmed

      • A role for mammalian Sin3 in permanent gene silencing. Mol Cell. 2008 Nov 07; 32(3):359-70. View in: Pubmed

      • Kinase requirements in human cells: III. Altered kinase requirements in VHL-/- cancer cells detected in a pilot synthetic lethal screen. Proc Natl Acad Sci U S A. 2008 Oct 28; 105(43):16484-9. View in: Pubmed

      • The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer. Nat Rev Cancer. 2008 Nov; 8(11):865-73. View in: Pubmed

      • Senescence triggered by the loss of the VHL tumor suppressor. Cell Cycle. 2008 Jun 15; 7(12):1709-12. View in: Pubmed

      • Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell. 2008 May 23; 30(4):393-402. View in: Pubmed

      • The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor. Genes Dev. 2008 Apr 01; 22(7):884-93. View in: Pubmed

      • VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat Cell Biol. 2008 Mar; 10(3):361-9. View in: Pubmed

      • Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure. Blood. 2008 Mar 15; 111(6):3236-44. View in: Pubmed

      • Nineteenth Annual Pezcoller Symposium: hypothesis-driven clinical investigation in cancer. Cancer Res. 2007 Dec 01; 67(23):11102-5. View in: Pubmed

      • pVHL acts as an adaptor to promote the inhibitory phosphorylation of the NF-kappaB agonist Card9 by CK2. Mol Cell. 2007 Oct 12; 28(1):15-27. View in: Pubmed

      • Hypoxia-inducible factor linked to differential kidney cancer risk seen with type 2A and type 2B VHL mutations. Mol Cell Biol. 2007 Aug; 27(15):5381-92. View in: Pubmed

      • The retinoblastoma binding protein RBP2 is an H3K4 demethylase. Cell. 2007 Mar 09; 128(5):889-900. View in: Pubmed

      • Innovations and challenges in renal cell carcinoma: summary statement from the Second Cambridge Conference. Clin Cancer Res. 2007 Jan 15; 13(2 Pt 2):667s-670s. View in: Pubmed

      • The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Clin Cancer Res. 2007 Jan 15; 13(2 Pt 2):680s-684s. View in: Pubmed

      • The hypoxia-inducible factor 2alpha N-terminal and C-terminal transactivation domains cooperate to promote renal tumorigenesis in vivo. Mol Cell Biol. 2007 Mar; 27(6):2092-102. View in: Pubmed

      • Von Hippel-Lindau disease. Annu Rev Pathol. 2007; 2:145-73. View in: Pubmed

      • The von hippel-lindau tumor suppressor protein: an update. Methods Enzymol. 2007; 435:371-83. View in: Pubmed

      • Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit. Nat Cell Biol. 2007 Feb; 9(2):225-32. View in: Pubmed

      • Molecular pathways in renal cell carcinoma--rationale for targeted treatment. Semin Oncol. 2006 Oct; 33(5):588-95. View in: Pubmed

      • Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo. EMBO J. 2006 Oct 04; 25(19):4650-62. View in: Pubmed

      • Cell biology: divining cancer cell weaknesses. Nature. 2006 May 04; 441(7089):32-4. View in: Pubmed

      • Clusterin is a secreted marker for a hypoxia-inducible factor-independent function of the von Hippel-Lindau tumor suppressor protein. Am J Pathol. 2006 Feb; 168(2):574-84. View in: Pubmed

      • Recent insights into the molecular pathogenesis of pheochromocytoma and paraganglioma. Endocr Pathol. 2006; 17(2):97-106. View in: Pubmed

      • Mouse model for noninvasive imaging of HIF prolyl hydroxylase activity: assessment of an oral agent that stimulates erythropoietin production. Proc Natl Acad Sci U S A. 2006 Jan 03; 103(1):105-10. View in: Pubmed

      • The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer. 2005 Sep; 5(9):689-98. View in: Pubmed

      • The von Hippel-Lindau protein, HIF hydroxylation, and oxygen sensing. Biochem Biophys Res Commun. 2005 Dec 09; 338(1):627-38. View in: Pubmed

      • Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer. Cancer Cell. 2005 Aug; 8(2):155-67. View in: Pubmed

      • The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase. Cancer Cell. 2005 Jul; 8(1):25-33. View in: Pubmed

      • Binding of pRB to the PHD protein RBP2 promotes cellular differentiation. Mol Cell. 2005 Jun 10; 18(6):623-35. View in: Pubmed

      • ROS: really involved in oxygen sensing. Cell Metab. 2005 Jun; 1(6):357-8. View in: Pubmed

      • Bioluminescent imaging of ubiquitin ligase activity: measuring Cdk2 activity in vivo through changes in p27 turnover. Methods Enzymol. 2005; 399:530-49. View in: Pubmed

      • The von Hippel-Lindau tumor suppressor protein: roles in cancer and oxygen sensing. Cold Spring Harb Symp Quant Biol. 2005; 70:159-66. View in: Pubmed

      • Proline hydroxylation and gene expression. Annu Rev Biochem. 2005; 74:115-28. View in: Pubmed

      • Role of VHL gene mutation in human cancer. J Clin Oncol. 2004 Dec 15; 22(24):4991-5004. View in: Pubmed

      • Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia response element antagonist. Proc Natl Acad Sci U S A. 2004 Nov 30; 101(48):16768-73. View in: Pubmed

      • Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev. 2004 Dec 01; 18(23):2893-904. View in: Pubmed

      • The von Hippel-Lindau tumor suppressor gene and kidney cancer. Clin Cancer Res. 2004 Sep 15; 10(18 Pt 2):6290S-5S. View in: Pubmed

      • Innovations and challenges in renal cancer: consensus statement from the first international conference. Clin Cancer Res. 2004 Sep 15; 10(18 Pt 2):6277S-81S. View in: Pubmed

      • Dysregulation of HIF and VEGF is a unifying feature of the familial hamartoma syndromes. Cancer Cell. 2004 Jul; 6(1):7-10. View in: Pubmed

      • Bioluminescent imaging of Cdk2 inhibition in vivo. Nat Med. 2004 Jun; 10(6):643-8. View in: Pubmed

      • Proceedings of the Oxygen Homeostasis/Hypoxia Meeting. Cancer Res. 2004 May 01; 64(9):3350-6. View in: Pubmed

      • Fifteenth annual Pezcoller symposium: molecular in vivo visualization of cancer cells. Cancer Res. 2004 Apr 15; 64(8):2929-33. View in: Pubmed

      • pVHL modification by NEDD8 is required for fibronectin matrix assembly and suppression of tumor development. Mol Cell Biol. 2004 Apr; 24(8):3251-61. View in: Pubmed

      • Gleevec: prototype or outlier? Sci STKE. 2004 Mar 16; 2004(225):pe12. View in: Pubmed

      • Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex. Nature. 2004 Mar 11; 428(6979):194-8. View in: Pubmed

      • Analysis of von Hippel-Lindau hereditary cancer syndrome: implications of oxygen sensing. Methods Enzymol. 2004; 381:320-35. View in: Pubmed

      • Inhibition of HIF2alpha is sufficient to suppress pVHL-defective tumor growth. PLoS Biol. 2003 Dec; 1(3):E83. View in: Pubmed

      • The von Hippel-Lindau gene, kidney cancer, and oxygen sensing. J Am Soc Nephrol. 2003 Nov; 14(11):2703-11. View in: Pubmed

      • Mouse reporter strain for noninvasive bioluminescent imaging of cells that have undergone Cre-mediated recombination. Mol Imaging. 2003 Oct; 2(4):297-302. View in: Pubmed

      • TSC2 regulates VEGF through mTOR-dependent and -independent pathways. Cancer Cell. 2003 Aug; 4(2):147-58. View in: Pubmed

      • The von Hippel-Lindau protein, vascular endothelial growth factor, and kidney cancer. N Engl J Med. 2003 Jul 31; 349(5):419-21. View in: Pubmed

      • E2F1 as a target: promoter-driven suicide and small molecule modulators. Cancer Biol Ther. 2003 Jul-Aug; 2(4 Suppl 1):S48-54. View in: Pubmed

      • Chemosensitivity linked to p73 function. Cancer Cell. 2003 Apr; 3(4):403-10. View in: Pubmed

      • Gene expression profiling in a renal cell carcinoma cell line: dissecting VHL and hypoxia-dependent pathways. Mol Cancer Res. 2003 Apr; 1(6):453-62. View in: Pubmed

      • HIF hydroxylation and the mammalian oxygen-sensing pathway. J Clin Invest. 2003 Mar; 111(6):779-83. View in: Pubmed

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      Dana-Farber Cancer Institute

      Location Avtar

      Dana-Farber Cancer Institute

      450 Brookline Avenue Mayer 457 Boston, MA 02215
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      42.3374, -71.1082