Photo of William G. Kaelin,  Jr., MD

William G. Kaelin, Jr., MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-3975
Fax: (617) 632-4760

William G. Kaelin, Jr., MD

Dana-Farber Cancer Institute


  • Professor, Medicine, Harvard Medical School
  • Senior Physician, Medicine, Brigham And Women's Hospital



  • Member, Center Scientific Council
  • Associate Director, Basic Science, Executive Committee

Research Abstract

The Kaelin Laboratory studies the functions of tumor suppressor proteins including the retinoblastoma protein (pRB), the von Hippel-Lindau protein (pVHL), and a homolog of the p53 tumor suppressor protein called p73. The laboratory uses a variety of molecular and cellular approaches to understand how, mechanistically, these proteins prevent tumor growth. One long term goal of this work is to lay the foundation for novel anticancer strategies. For example, one could envision the development of drugs that will selectively kill cells that lack a particular tumor suppressor protein or which will mimic a particular biochemical activity normally performed by a tumor suppressor protein.


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  • Kaelin WG. DisABLing kidney cancers caused by fumarate hydratase mutations. Cancer Cell 2014; 26:779-80. PubMed
  • Lu G, Zhang Q, Huang Y, Song J, Tomaino R, Ehrenberger T, Lim E, Liu W, Bronson RT, Bowden M, Brock J, Krop IE, Dillon DA, Gygi SP, Mills GB, Richardson AL, Signoretti S, Yaffe MB, Kaelin WG. Phosphorylation of ETS1 by Src family kinases prevents its recognition by the COP1 tumor suppressor. Cancer Cell 2014; 26:222-34. PubMed
  • Zheng X, Zhai B, Koivunen P, Shin SJ, Lu G, Liu J, Geisen C, Chakraborty AA, Moslehi JJ, Smalley DM, Wei X, Chen X, Chen Z, Beres JM, Zhang J, Tsao JL, Brenner MC, Zhang Y, Fan C, DePinho RA, Paik J, Gygi SP, Kaelin WG, Zhang Q. Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase. Genes Dev 2014; 28:1429-44. PubMed
  • Akbay EA, Moslehi J, Christensen CL, Saha S, Tchaicha JH, Ramkissoon SH, Stewart KM, Carretero J, Kikuchi E, Zhang H, Cohoon TJ, Murray S, Liu W, Uno K, Fisch S, Jones K, Gurumurthy S, Gliser C, Choe S, Keenan M, Son J, Stanley I, Losman JA, Padera R, Bronson RT, Asara JM, Abdel-Wahab O, Amrein PC, Fathi AT, Danial NN, Kimmelman AC, Kung AL, Ligon KL, Yen KE, Kaelin WG, Bardeesy N, Wong KK. D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice. Genes Dev 2014; 28:479-90. PubMed
  • Lu G, Middleton RE, Sun H, Naniong M, Ott CJ, Mitsiades CS, Wong KK, Bradner JE, Kaelin WG. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science 2014; 343:305-9. PubMed
  • Li L, Shen C, Nakamura E, Ando K, Signoretti S, Beroukhim R, Cowley GS, Lizotte P, Liberzon E, Bair S, Root DE, Tamayo P, Tsherniak A, Cheng SC, Tabak B, Jacobsen A, Hakimi AA, Schultz N, Ciriello G, Sander C, Hsieh JJ, Kaelin WG. SQSTM1 is a pathogenic target of 5q copy number gains in kidney cancer. Cancer Cell 2013; 24:738-50. PubMed
  • Losman JA, Looper RE, Koivunen P, Lee S, Schneider RK, McMahon C, Cowley GS, Root DE, Ebert BL, Kaelin WG. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science 2013; 339:1621-5. PubMed
  • Kaelin WG, McKnight SL. Influence of metabolism on epigenetics and disease. Cell 2013; 153:56-69. PubMed
  • Beshiri ML, Holmes KB, Richter WF, Hess S, Islam AB, Yan Q, Plante L, Litovchick L, GĂ©vry N, Lopez-Bigas N, Kaelin WG, Benevolenskaya EV. Coordinated repression of cell cycle genes by KDM5A and E2F4 during differentiation. Proc Natl Acad Sci U S A 2012; 109:18499-504. PubMed
  • Kaelin WG. Molecular biology. Use and abuse of RNAi to study mammalian gene function. Science 2012; 337:421-2. PubMed
  • Shen C, Kaelin WG. The VHL/HIF axis in clear cell renal carcinoma. Semin Cancer Biol 2012. PubMed
  • Wei W, Kaelin WG. Good COP1 or bad COP1? In vivo veritas. J Clin Invest 2011. PubMed
  • Rogers LR, LoRusso P, Nadler P, Malik G, Shields A, Kaelin W. Erlotinib therapy for central nervous system hemangioblastomatosis associated with von Hippel-Lindau disease: a case report. J. Neurooncol. 2010; 101:307-10. PubMed
  • Astuti D, Ricketts C, Chowdury R, McDonough MA, Gentle D, Kirby G, Schlisio S, Kenchappa R, Carter B, Kaelin WG, Ratcliffe PJ, Schofield CJ, Latif F, Maher E. Mutation analysis of HIF-prolylhydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility. Endocr. Relat. Cancer 2010; 18:73-83. PubMed
  • Gan B, Lim C, Chu G, Hua S, Ding Z, Collins M, Hu J, Jiang S, Fletcher-Sananikone E, Zhuang L, Chang M, Zheng H, Wang YA, Kwiatkowski DJ, Kaelin WG, Signoretti S, DePinho RA. FoxOs enforce a progression checkpoint to constrain mTORC1-activated renal tumorigenesis. Cancer Cell 2010; 18:472-84. PubMed
  • Kaelin WG. New cancer targets emerging from studies of the Von Hippel-Lindau tumor suppressor protein. Ann N Y Acad Sci 2010; 1210:1-7. PubMed
  • Moslehi J, Minamishima YA, Shi J, Neuberg D, Charytan DM, Padera RF, Signoretti S, Liao R, Kaelin WG. Loss of hypoxia-inducible factor prolyl hydroxylase activity in cardiomyocytes phenocopies ischemic cardiomyopathy. Circulation 2010; 122:1004-16. PubMed
  • Inuzuka H, Tseng A, Gao D, Zhai B, Zhang Q, Shaik S, Wan L, Ang XL, Mock C, Yin H, Stommel JM, Gygi S, Lahav G, Asara J, Xiao ZX, Kaelin WG, Harper JW, Wei W. Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase. Cancer Cell 2010; 18:147-59. PubMed
  • Minamishima YA, Kaelin WG. Reactivation of hepatic EPO synthesis in mice after PHD loss. Science 2010; 329:407. PubMed
  • Kaelin WG, Thompson CB. Q&A: Cancer: clues from cell metabolism. Nature 2010; 465:562-4. PubMed
  • Sorrell A, Lee S, Stolle C, Ellenhorn J, Grix A, Kaelin W, Weitzel J. Clinical and functional properties of novel VHL mutation (X214L) consistent with Type 2A phenotype and low risk of renal cell carcinoma. Clin Genet 2010. PubMed
  • Loda M, Kaelin WG. Prostate cancer: beta control your hormones. Cancer Cell 2010; 17:311-2. PubMed
  • Bommi-Reddy A, Kaelin WG. Slaying RAS with a synthetic lethal weapon. Cell Res 2010; 20:119-21. PubMed
  • Zhang Q, Gu J, Li L, Liu J, Luo B, Cheung HW, Boehm JS, Ni M, Geisen C, Root DE, Polyak K, Brown M, Richardson AL, Hahn WC, Kaelin WG, Bommi-Reddy A. Control of cyclin D1 and breast tumorigenesis by the EglN2 prolyl hydroxylase. Cancer Cell 2009; 16:413-24. PubMed
  • Minamishima YA, Moslehi J, Padera RF, Bronson RT, Liao R, Kaelin WG. A feedback loop involving the Phd3 prolyl hydroxylase tunes the mammalian hypoxic response in vivo. Mol Cell Biol 2009; 29:5729-41. PubMed
  • Kaelin WG. SDH5 mutations and familial paraganglioma: somewhere Warburg is smiling. Cancer Cell 2009; 16:180-2. PubMed
  • Kim WY, Perera S, Zhou B, Carretero J, Yeh JJ, Heathcote SA, Jackson AL, Nikolinakos P, Ospina B, Naumov G, Brandstetter KA, Weigman VJ, Zaghlul S, Hayes DN, Padera RF, Heymach JV, Kung AL, Sharpless NE, Kaelin WG, Wong KK. HIF2alpha cooperates with RAS to promote lung tumorigenesis in mice. J Clin Invest 2009; 119:2160-70. PubMed
  • Beroukhim R,Brunet JP,Di Napoli A,Mertz KD,Seeley A,Pires MM,Linhart D,Worrell RA,Moch H,Rubin MA,Sellers WR,Meyerson M,Linehan WM,Kaelin WG Jr,Signoretti S. 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; 69:4674-4681. PubMed
  • Kaelin WG. Treatment of kidney cancer: insights provided by the VHL tumor-suppressor protein. Cancer 2009; 115:2262-72. PubMed
  • Atkins MB, Bukowski RM, Escudier BJ, Figlin RA, Hudes GH, Kaelin WG, Linehan WM, McDermott DF, Mier JW, Pedrosa I, Rini BI, Signoretti S, Sosman JA, Teh BT, Wood CG, Zurita AJ, King L. Innovations and challenges in renal cancer: summary statement from the Third Cambridge Conference. Cancer 2009; 115:2247-51. PubMed
  • Kaelin WG. Synthetic lethality: a framework for the development of wiser cancer therapeutics. Genome Med 2009; 1:99. PubMed
  • Kaelin WG. Kidney cancer: now available in a new flavor. Cancer Cell 2008; 14:423-4. PubMed
  • van Oevelen C, Wang J, Asp P, Yan Q, Kaelin WG, Kluger Y, Dynlacht BD. A role for mammalian Sin3 in permanent gene silencing. Mol Cell 2008; 32:359-70. PubMed
  • Kaelin WG. The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer. Nat Rev Cancer 2008; 8:865-73. PubMed
  • Bommi-Reddy A, Almeciga I, Sawyer J, Geisen C, Li W, Harlow E, Kaelin WG, Grueneberg DA. 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; 105:16484-9. PubMed
  • Young AP, Kaelin WG. Senescence triggered by the loss of the VHL tumor suppressor. Cell Cycle 2008; 7:1709-12. PubMed
  • Kaelin WG, Ratcliffe PJ. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 2008; 30:393-402. PubMed
  • Schlisio S, Kenchappa RS, Vredeveld LC, George RE, Stewart R, Greulich H, Shahriari K, Nguyen NV, Pigny P, Dahia PL, Pomeroy SL, Maris JM, Look AT, Meyerson M, Peeper DS, Carter BD, Kaelin WG Jr. The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor. Genes Dev 2008; 22:884-93. PubMed
  • Minamishima YA, Moslehi J, Bardeesy N, Cullen D, Bronson RT, Kaelin WG. Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure. Blood 2007; 111:3236-44. PubMed
  • Young AP, Schlisio S, Minamishima YA, Zhang Q, Li L, Grisanzio C, Signoretti S, Kaelin WG Jr. VHL loss actuates a HIF-independent senescence programme mediated by Rb and p400. Nat Cell Biol 2008; 10:361-9. PubMed
  • Kaelin WG, Sawyers CL, Mihich E. Nineteenth Annual Pezcoller Symposium: hypothesis-driven clinical investigation in cancer. Cancer Res 2007; 67:11102-5. PubMed
  • Yang H, Minamishima YA, Yan Q, Schlisio S, Ebert BL, Zhang X, Zhang L, Kim WY, Olumi AF, Kaelin WG. pVHL acts as an adaptor to promote the inhibitory phosphorylation of the NF-kappaB agonist Card9 by CK2. Mol Cell 2007; 28:15-27. PubMed
  • Li L, Zhang L, Zhang X, Yan Q, Minamishima YA, Olumi AF, Mao M, Bartz S, Kaelin WG. HIF LINKED TO DIFFERENTIAL KIDNEY CANCER RISK SEEN WITH TYPE 2A AND TYPE 2B VHL MUTATIONS. Mol Cell Biol 2007; 27:5381-92. PubMed
  • Klose RJ, Yan Q, Tothova Z, Yamane K, Erdjument-Bromage H, Tempst P, Gilliland DG, Zhang Y, Kaelin WG. The retinoblastoma binding protein RBP2 is an H3K4 demethylase. Cell 2007; 128:889-900. PubMed
  • Yan Q, Bartz S, Mao M, Li L, Kaelin WG. The hypoxia-inducible factor 2alpha N-terminal and C-terminal transactivation domains cooperate to promote renal tumorigenesis in vivo. Mol Cell Biol 2007; 27:2092-102. PubMed
  • Atkins MB, Ernstoff MS, Figlin RA, Flaherty KT, George DJ, Kaelin WG, Kwon ED, Libermann TA, Linehan WM, McDermott DF, Ochoa AC, Pantuck AJ, Rini BI, Rosen MA, Sosman JA, Sukhatme VP, Vieweg JW, Wood CG, King L. Innovations and challenges in renal cell carcinoma: summary statement from the second cambridge conference. Clin Cancer Res 2007; 13:667s-70s. PubMed
  • Kaelin WG. The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Clin Cancer Res 2007; 13:680s-684s. PubMed
  • Kaelin WG. The von hippel-lindau tumor suppressor protein: an update. Methods Enzymol 2007; 435:371-83. PubMed
  • Kaelin WG. Von Hippel-Lindau disease. Annu Rev Pathol 2007; 2:145-73. PubMed
  • Kim WY, Safran M, Buckley MR, Ebert BL, Glickman J, Bosenberg M, Regan M, Kaelin WG. Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo. EMBO J 2006; 25:4650-62. PubMed
  • Kim WY, Kaelin WG. Molecular pathways in renal cell carcinoma--rationale for targeted treatment. Semin Oncol 2006; 33:588-95. PubMed
  • Safran M, Kim W, O'Connell F, Flippin L, Gunzler V, Horner J, Depinho R, Kaelin WG. A phase I/II trial of sorafenib (S) with bevacizumab (B) in metastatic renal cell cancer (mRCC) patients (Pts). ASCO Annual Meeting Proceedings 2006; 24:3031.
  • Nakamura E, Kaelin WG. Recent insights into the molecular pathogenesis of pheochromocytoma and paraganglioma. Endocr Pathol 2006; 17:97-106. PubMed
  • Kaelin WG. Cell biology: divining cancer cell weaknesses. Nature 2006; 441:32-4. PubMed
  • Nakamura E, Abreu-e-Lima P, Awakura Y, Inoue T, Kamoto T, Ogawa O, Kotani H, Manabe T, Zhang GJ, Kondo K, Nose V, Kaelin WG Jr.. Clusterin is a secreted marker for a hypoxia-inducible factor-independent function of the von Hippel-Lindau tumor suppressor protein. Am J Clin Pathol 2006; 168:574-84.
  • Kaelin WG. The von hippel-lindau tumor suppressor protein: roles in cancer and oxygen sensing. Cold Spring Harb Symp Quant Biol 2006; 70:159-66. PubMed
  • Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin WG. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 2004; 18:2893-904. PubMed
  • Atkins MB, Avigan DE, Bukowski RM, Childs RW, Dutcher JP, Eisen TG, Figlin RA, Finke JH, Flanigan RC, George DJ, Goldberg SN, Gordon MS, Iliopoulos O, Kaelin WG, Linehan WM, Lipton A, Motzer RJ, Novick AC, Stadler WM, Teh BT, Yang JC, King L. Innovations and challenges in renal cancer: consensus statement from the first international conference. Clin Cancer Res 2004; 10:6277S-81S. PubMed
  • Stickle NH, Chung J, Klco JM, Hill RP, Kaelin WG, Ohh M. pVHL modification by NEDD8 is required for fibronectin matrix assembly and suppression of tumor development. Mol Cell Biol 2004; 24:3251-61. PubMed
  • Ohh M, Kim WY, Moslehi JJ, Chen Y, Chau V, Read MA, Kaelin WG. An intact NEDD8 pathway is required for Cullin-dependent ubiquitylation in mammalian cells. EMBO Rep 2002; 3:177-82. PubMed