William Querbes


Affiliation: Harvard University
Country: USA


  1. request reprint
    Kaelin W. The concept of synthetic lethality in the context of anticancer therapy. Nat Rev Cancer. 2005;5:689-98 pubmed
    ..This is changing as a result of the increased availability of chemical and genetic tools for perturbing gene function in somatic cells. ..
  2. Suhara T, Hishiki T, Kasahara M, Hayakawa N, Oyaizu T, Nakanishi T, et al. 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;112:11642-7 pubmed publisher
    ..These data suggest that PHD2 is a potentially novel drug target for the treatment of lactic acidosis, which is a serious and often fatal complication observed in some critically ill patients. ..
  3. Chakraborty A, Laukka T, Myllykoski M, Ringel A, Booker M, Tolstorukov M, et al. Histone demethylase KDM6A directly senses oxygen to control chromatin and cell fate. Science. 2019;363:1217-1222 pubmed publisher
    ..Restoring H3K27 methylation homeostasis in hypoxic cells reversed these effects. Thus, oxygen directly affects chromatin regulators to control cell fate. ..
  4. Koduri V, McBrayer S, Liberzon E, Wang A, Briggs K, Cho H, et al. Peptidic degron for IMiD-induced degradation of heterologous proteins. Proc Natl Acad Sci U S A. 2019;116:2539-2544 pubmed publisher
  5. Oser M, Fonseca R, Chakraborty A, Brough R, Spektor A, Jennings R, et al. Cells Lacking the RB1 Tumor Suppressor Gene Are Hyperdependent on Aurora B Kinase for Survival. Cancer Discov. 2019;9:230-247 pubmed publisher
    ..i>See related commentary by Dick and Li, p. 169.This article is highlighted in the In This Issue feature, p. 151. ..
  6. McBrayer S, Mayers J, DiNatale G, Shi D, Khanal J, Chakraborty A, et al. Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma. Cell. 2018;175:101-116.e25 pubmed publisher
  7. Kaelin W. DisABLing kidney cancers caused by fumarate hydratase mutations. Cancer Cell. 2014;26:779-780 pubmed publisher
    ..In this issue of Cancer Cell, Sourbier and colleagues show that kidney cancers lacking fumarate hydratase display increased sensitivity to agents that interfere with their ability to cope with reactive oxygen species. ..
  8. McBrayer S, Olenchock B, DiNatale G, Shi D, Khanal J, Jennings R, et al. Autochthonous tumors driven by Rb1 loss have an ongoing requirement for the RBP2 histone demethylase. Proc Natl Acad Sci U S A. 2018;115:E3741-E3748 pubmed publisher
    ..These findings show that established Rb1-null tumors require RBP2 for growth and further credential RBP2 as a therapeutic target in human cancers driven by RB1 inactivation. ..
  9. Kaelin W. 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 pubmed publisher
    ..2-Oxoglutarate-dependent dioxygenases therefore provide a link between altered metabolism and cancer. ..

More Information


  1. request reprint
    Kaelin W. Proline hydroxylation and gene expression. Annu Rev Biochem. 2005;74:115-28 pubmed
    ..The existence of three human EGLN family members, as well as other putative hydroxylases, raises the possibility that this signal is used in other contexts by other proteins. ..
  2. Kaelin W, Ratcliffe P. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell. 2008;30:393-402 pubmed publisher
    ..HIF affects signaling pathways that influence development, metabolism, inflammation, and integrative physiology. Accordingly, HIF-modulatory drugs are now being developed for diverse diseases. ..
  3. Olenchock B, Moslehi J, Baik A, Davidson S, Williams J, Gibson W, et al. EGLN1 Inhibition and Rerouting of α-Ketoglutarate Suffice for Remote Ischemic Protection. Cell. 2016;164:884-95 pubmed publisher
    ..Egln1 loss causes accumulation of circulating αKG, which drives hepatic production and secretion of kynurenic acid (KYNA) that is necessary and sufficient to mediate cardiac ischemic protection in this setting. ..
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    Kaelin W. The von Hippel-Lindau tumor suppressor gene and kidney cancer. Clin Cancer Res. 2004;10:6290S-5S pubmed
    ..Genotype-phenotype correlations in VHL disease suggest, however, that pVHL has targets in addition to HIF. Elucidating these targets should provide a more complete picture of how pVHL suppresses tumor growth. ..
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    Kaelin W. The von Hippel-Lindau tumor suppressor protein and clear cell renal carcinoma. Clin Cancer Res. 2007;13:680s-684s pubmed
  6. Chakraborty A, Nakamura E, Qi J, Creech A, Jaffe J, Paulk J, et al. HIF activation causes synthetic lethality between the VHL tumor suppressor and the EZH1 histone methyltransferase. Sci Transl Med. 2017;9: pubmed publisher
    ..Therefore, targeting EZH1 could be therapeutically useful in ccRCC. ..
  7. Gao W, Li W, Xiao T, Liu X, Kaelin W. 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;114:1027-1032 pubmed publisher
    ..Biochemical and functional studies linked growth suppression by BAF180 to its ability to form a canonical PBAF complex containing BRG1 that dampens the HIF transcriptional signature. ..
  8. Briggs K, Koivunen P, Cao S, Backus K, Olenchock B, Patel H, et al. Paracrine Induction of HIF by Glutamate in Breast Cancer: EglN1 Senses Cysteine. Cell. 2016;166:126-39 pubmed publisher
    ..EglN1, the main HIF? prolyl-hydroxylase, undergoes oxidative self-inactivation in the absence of cysteine both in biochemical assays and in cells, resulting in HIF1? accumulation. Therefore, EglN1 senses both oxygen and cysteine. ..
  9. Zhang C, Li X, Adelmant G, Dobbins J, Geisen C, Oser M, et al. 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;112:15372-7 pubmed publisher
  10. Kaelin W. SDH5 mutations and familial paraganglioma: somewhere Warburg is smiling. Cancer Cell. 2009;16:180-2 pubmed publisher
    ..Moreover, they detected SDH5 mutations in a large kindred with familial paraganglioma. ..
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    Kaelin W. The emerging p53 gene family. J Natl Cancer Inst. 1999;91:594-8 pubmed
    ..Additional studies are required to determine the role, if any, that p73 and p51 play in cell growth control and carcinogenesis. ..
  12. Lu G, Zhang Q, Huang Y, Song J, Tomaino R, Ehrenberger T, et al. Phosphorylation of ETS1 by Src family kinases prevents its recognition by the COP1 tumor suppressor. Cancer Cell. 2014;26:222-34 pubmed publisher
    ..These findings expand the list of potential COP1 substrates to include proteins whose COP1-binding sites are subject to regulatory phosphorylation and provide insights into transformation by Src family kinases. ..
  13. Kaelin W, McKnight S. Influence of metabolism on epigenetics and disease. Cell. 2013;153:56-69 pubmed publisher
    ..Here, we review literature pertinent to hypothetical connections between metabolic and epigenetic states in eukaryotic cells. ..
  14. Kaelin W. Molecular biology. Use and abuse of RNAi to study mammalian gene function. Science. 2012;337:421-2 pubmed publisher
  15. Querbes W, Bogorad R, Moslehi J, Wong J, Chan A, Bulgakova E, et al. Treatment of erythropoietin deficiency in mice with systemically administered siRNA. Blood. 2012;120:1916-22 pubmed publisher