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profileJohnathan Whetstine, Ph.D.

TitleAssociate Professor of Medicine
InstitutionMassachusetts General Hospital
DepartmentMedicine
AddressMassachusetts General Hospital
Ctr for Cancer Research, 7-213
149 13th Street
Charlestown MA 02129
Phone617/643-4373
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Collapse Research 
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The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
R01GM097360     (WHETSTINE, JOHNATHAN R.)Feb 1, 2012 - Dec 31, 2020
NIH/NIGMS
Understanding chromatin modulation of copy number and rereplication
Role: Principal Investigator

F32GM070095     (WHETSTINE, JOHNATHAN R.)Feb 1, 2004 - Jan 31, 2007
NIH/NIGMS
The Role of Chromatin Modification During Development
Role: Principal Investigator

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Collapse selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Wang M, Han J, Marcar L, Black J, Liu Q, Li X, Nagulapalli K, Sequist LV, Mak RH, Benes CH, Hong TS, Gurtner K, Krause M, Baumann M, Kang JX, Whetstine JR, Willers H. Radiation Resistance in KRAS-Mutated Lung Cancer Is Enabled by Stem-like Properties Mediated by an Osteopontin-EGFR Pathway. Cancer Res. 2017 Apr 15; 77(8):2018-2028. PMID: 28202526.
    View in: PubMed
  2. Black JC, Zhang H, Kim J, Getz G, Whetstine JR. Regulation of Transient Site-specific Copy Gain by MicroRNA. J Biol Chem. 2016 Mar 04; 291(10):4862-71. PMID: 26755726; PMCID: PMC4777823.
  3. Mishra S, Whetstine JR. Different Facets of Copy Number Changes: Permanent, Transient, and Adaptive. Mol Cell Biol. 2016 Jan 11; 36(7):1050-63. PMID: 26755558; PMCID: PMC4800790.
  4. Black JC, Whetstine JR. RNF2 E3 or Not to E3: Dual Roles of RNF2 Overexpression in Melanoma. Cancer Discov. 2015 Dec; 5(12):1241-3. PMID: 26637658; PMCID: PMC4733319.
  5. Wagschal A, Najafi-Shoushtari SH, Wang L, Goedeke L, Sinha S, deLemos AS, Black JC, Ramírez CM, Li Y, Tewhey R, Hatoum I, Shah N, Lu Y, Kristo F, Psychogios N, Vrbanac V, Lu YC, Hla T, de Cabo R, Tsang JS, Schadt E, Sabeti PC, Kathiresan S, Cohen DE, Whetstine J, Chung RT, Fernández-Hernando C, Kaplan LM, Bernards A, Gerszten RE, Näär AM. Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis. Nat Med. 2015 Nov; 21(11):1290-7. PMID: 26501192; PMCID: PMC4993048.
  6. Tajima K, Yae T, Javaid S, Tam O, Comaills V, Morris R, Wittner BS, Liu M, Engstrom A, Takahashi F, Black JC, Ramaswamy S, Shioda T, Hammell M, Haber DA, Whetstine JR, Maheswaran S. SETD1A modulates cell cycle progression through a miRNA network that regulates p53 target genes. Nat Commun. 2015 Sep 23; 6:8257. PMID: 26394836; PMCID: PMC4667427.
  7. Black JC, Whetstine JR. Too little O2 Too much gain. Cell Cycle. 2015; 14(18):2869-70. PMID: 26221746; PMCID: PMC4825632.
  8. Black JC, Atabakhsh E, Kim J, Biette KM, Van Rechem C, Ladd B, Burrowes PD, Donado C, Mattoo H, Kleinstiver BP, Song B, Andriani G, Joung JK, Iliopoulos O, Montagna C, Pillai S, Getz G, Whetstine JR. Hypoxia drives transient site-specific copy gain and drug-resistant gene expression. Genes Dev. 2015 May 15; 29(10):1018-31. PMID: 25995187; PMCID: PMC4441050.
  9. Van Rechem C, Black JC, Greninger P, Zhao Y, Donado C, Burrowes PD, Ladd B, Christiani DC, Benes CH, Whetstine JR. A coding single-nucleotide polymorphism in lysine demethylase KDM4A associates with increased sensitivity to mTOR inhibitors. Cancer Discov. 2015 Mar; 5(3):245-54. PMID: 25564517; PMCID: PMC4355226.
  10. Van Rechem C, Black JC, Boukhali M, Aryee MJ, Gräslund S, Haas W, Benes CH, Whetstine JR. Lysine demethylase KDM4A associates with translation machinery and regulates protein synthesis. Cancer Discov. 2015 Mar; 5(3):255-63. PMID: 25564516; PMCID: PMC4355328.
  11. Whetstine JR. Methylation: a multifaceted modification - looking at transcription and beyond. Biochim Biophys Acta. 2014 Dec; 1839(12):1351-2. PMID: 25225044.
    View in: PubMed
  12. Van Rechem C, Whetstine JR. Examining the impact of gene variants on histone lysine methylation. Biochim Biophys Acta. 2014 Dec; 1839(12):1463-76. PMID: 24859469; PMCID: PMC4752941.
  13. Javaid S, Zhang J, Anderssen E, Black JC, Wittner BS, Tajima K, Ting DT, Smolen GA, Zubrowski M, Desai R, Maheswaran S, Ramaswamy S, Whetstine JR, Haber DA. Dynamic chromatin modification sustains epithelial-mesenchymal transition following inducible expression of Snail-1. Cell Rep. 2013 Dec 26; 5(6):1679-89. PMID: 24360956; PMCID: PMC4034764.
  14. Rottiers V, Obad S, Petri A, McGarrah R, Lindholm MW, Black JC, Sinha S, Goody RJ, Lawrence MS, deLemos AS, Hansen HF, Whittaker S, Henry S, Brookes R, Najafi-Shoushtari SH, Chung RT, Whetstine JR, Gerszten RE, Kauppinen S, Näär AM. Pharmacological inhibition of a microRNA family in nonhuman primates by a seed-targeting 8-mer antimiR. Sci Transl Med. 2013 Nov 20; 5(212):212ra162. PMID: 24259050; PMCID: PMC4033576.
  15. Black JC, Manning AL, Van Rechem C, Kim J, Ladd B, Cho J, Pineda CM, Murphy N, Daniels DL, Montagna C, Lewis PW, Glass K, Allis CD, Dyson NJ, Getz G, Whetstine JR. KDM4A lysine demethylase induces site-specific copy gain and rereplication of regions amplified in tumors. Cell. 2013 Aug 01; 154(3):541-55. PMID: 23871696; PMCID: PMC3832053.
  16. Birkelbach M, Ferraiolo N, Gheorghiu L, Pfäffle HN, Daly B, Ebright MI, Spencer C, O'Hara C, Whetstine JR, Benes CH, Sequist LV, Zou L, Dahm-Daphi J, Kachnic LA, Willers H. Detection of impaired homologous recombination repair in NSCLC cells and tissues. J Thorac Oncol. 2013 Mar; 8(3):279-86. PMID: 23399959; PMCID: PMC3573529.
  17. Black JC, Whetstine JR. Tipping the lysine methylation balance in disease. Biopolymers. 2013 Feb; 99(2):127-35. PMID: 23175387; PMCID: PMC3826254.
  18. Black JC, Van Rechem C, Whetstine JR. Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell. 2012 Nov 30; 48(4):491-507. PMID: 23200123; PMCID: PMC3861058.
  19. Korenjak M, Anderssen E, Ramaswamy S, Whetstine JR, Dyson NJ. RBF binding to both canonical E2F targets and noncanonical targets depends on functional dE2F/dDP complexes. Mol Cell Biol. 2012 Nov; 32(21):4375-87. PMID: 22927638; PMCID: PMC3486151.
  20. Black JC, Whetstine JR. LOX out, histones: a new enzyme is nipping at your tails. Mol Cell. 2012 May 11; 46(3):243-4. PMID: 22578539.
    View in: PubMed
  21. Van Rechem C, Black JC, Abbas T, Allen A, Rinehart CA, Yuan GC, Dutta A, Whetstine JR. The SKP1-Cul1-F-box and leucine-rich repeat protein 4 (SCF-FbxL4) ubiquitin ligase regulates lysine demethylase 4A (KDM4A)/Jumonji domain-containing 2A (JMJD2A) protein. J Biol Chem. 2011 Sep 02; 286(35):30462-70. PMID: 21757720; PMCID: PMC3162406.
  22. Black JC, Whetstine JR. Chromatin landscape: methylation beyond transcription. Epigenetics. 2011 Jan; 6(1):9-15. PMID: 20855937; PMCID: PMC3052912.
  23. Black JC, Allen A, Van Rechem C, Forbes E, Longworth M, Tschöp K, Rinehart C, Quiton J, Walsh R, Smallwood A, Dyson NJ, Whetstine JR. Conserved antagonism between JMJD2A/KDM4A and HP1? during cell cycle progression. Mol Cell. 2010 Dec 10; 40(5):736-48. PMID: 21145482.
    View in: PubMed
  24. Walker AK, Yang F, Jiang K, Ji JY, Watts JL, Purushotham A, Boss O, Hirsch ML, Ribich S, Smith JJ, Israelian K, Westphal CH, Rodgers JT, Shioda T, Elson SL, Mulligan P, Najafi-Shoushtari H, Black JC, Thakur JK, Kadyk LC, Whetstine JR, Mostoslavsky R, Puigserver P, Li X, Dyson NJ, Hart AC, Näär AM. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev. 2010 Jul 01; 24(13):1403-17. PMID: 20595232; PMCID: PMC2895199.
  25. Sun Y, Jiang X, Xu Y, Ayrapetov MK, Moreau LA, Whetstine JR, Price BD. Histone H3 methylation links DNA damage detection to activation of the tumour suppressor Tip60. Nat Cell Biol. 2009 Nov; 11(11):1376-82. PMID: 19783983; PMCID: PMC2783526.
  26. Chen S, Whetstine JR, Ghosh S, Hanover JA, Gali RR, Grosu P, Shi Y. The conserved NAD(H)-dependent corepressor CTBP-1 regulates Caenorhabditis elegans life span. Proc Natl Acad Sci U S A. 2009 Feb 03; 106(5):1496-501. PMID: 19164523; PMCID: PMC2635826.
  27. Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, Iwase S, Alpatov R, Issaeva I, Canaani E, Roberts TM, Chang HY, Shi Y. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature. 2007 Oct 11; 449(7163):689-94. PMID: 17851529.
    View in: PubMed
  28. Chen Z, Zang J, Kappler J, Hong X, Crawford F, Wang Q, Lan F, Jiang C, Whetstine J, Dai S, Hansen K, Shi Y, Zhang G. Structural basis of the recognition of a methylated histone tail by JMJD2A. Proc Natl Acad Sci U S A. 2007 Jun 26; 104(26):10818-23. PMID: 17567753; PMCID: PMC1891149.
  29. Iwase S, Lan F, Bayliss P, de la Torre-Ubieta L, Huarte M, Qi HH, Whetstine JR, Bonni A, Roberts TM, Shi Y. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell. 2007 Mar 23; 128(6):1077-88. PMID: 17320160.
    View in: PubMed
  30. Shi Y, Whetstine JR. Dynamic regulation of histone lysine methylation by demethylases. Mol Cell. 2007 Jan 12; 25(1):1-14. PMID: 17218267.
    View in: PubMed
  31. Chen Z, Zang J, Whetstine J, Hong X, Davrazou F, Kutateladze TG, Simpson M, Mao Q, Pan CH, Dai S, Hagman J, Hansen K, Shi Y, Zhang G. Structural insights into histone demethylation by JMJD2 family members. Cell. 2006 May 19; 125(4):691-702. PMID: 16677698.
    View in: PubMed
  32. Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell. 2006 May 05; 125(3):467-81. PMID: 16603238.
    View in: PubMed
  33. Whetstine JR, Ceron J, Ladd B, Dufourcq P, Reinke V, Shi Y. Regulation of tissue-specific and extracellular matrix-related genes by a class I histone deacetylase. Mol Cell. 2005 May 13; 18(4):483-90. PMID: 15893731.
    View in: PubMed
  34. Payton SG, Whetstine JR, Ge Y, Matherly LH. Transcriptional regulation of the human reduced folate carrier promoter C: synergistic transactivation by Sp1 and C/EBP beta and identification of a downstream repressor. Biochim Biophys Acta. 2005 Jan 21; 1727(1):45-57. PMID: 15652157.
    View in: PubMed
  35. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004 Dec 29; 119(7):941-53. PMID: 15620353.
    View in: PubMed
  36. Liu M, Whetstine JR, Payton SG, Ge Y, Flatley RM, Matherly LH. Roles of USF, Ikaros and Sp proteins in the transcriptional regulation of the human reduced folate carrier B promoter. Biochem J. 2004 Oct 15; 383(Pt 2):249-57. PMID: 15214842; PMCID: PMC1134065.
  37. Shi Y, Sawada J, Sui G, Affar el B, Whetstine JR, Lan F, Ogawa H, Luke MP, Nakatani Y, Shi Y. Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature. 2003 Apr 17; 422(6933):735-8. PMID: 12700765.
    View in: PubMed
  38. Gifford AJ, Haber M, Witt TL, Whetstine JR, Taub JW, Matherly LH, Norris MD. Role of the E45K-reduced folate carrier gene mutation in methotrexate resistance in human leukemia cells. Leukemia. 2002 Dec; 16(12):2379-87. PMID: 12454742.
    View in: PubMed
  39. Whetstine JR, Flatley RM, Matherly LH. The human reduced folate carrier gene is ubiquitously and differentially expressed in normal human tissues: identification of seven non-coding exons and characterization of a novel promoter. Biochem J. 2002 Nov 01; 367(Pt 3):629-40. PMID: 12144527; PMCID: PMC1222932.
  40. Whetstine JR, Witt TL, Matherly LH. The human reduced folate carrier gene is regulated by the AP2 and sp1 transcription factor families and a functional 61-base pair polymorphism. J Biol Chem. 2002 Nov 15; 277(46):43873-80. PMID: 12228234.
    View in: PubMed
  41. Whetstine JR, Gifford AJ, Witt T, Liu XY, Flatley RM, Norris M, Haber M, Taub JW, Ravindranath Y, Matherly LH. Single nucleotide polymorphisms in the human reduced folate carrier: characterization of a high-frequency G/A variant at position 80 and transport properties of the His(27) and Arg(27) carriers. Clin Cancer Res. 2001 Nov; 7(11):3416-22. PMID: 11705857.
    View in: PubMed
  42. Ding BC, Whetstine JR, Witt TL, Schuetz JD, Matherly LH. Repression of human reduced folate carrier gene expression by wild type p53. J Biol Chem. 2001 Mar 23; 276(12):8713-9. PMID: 11106643.
    View in: PubMed
  43. Whetstine JR, Matherly LH. The basal promoters for the human reduced folate carrier gene are regulated by a GC-box and a cAMP-response element/AP-1-like element. Basis for tissue-specific gene expression. J Biol Chem. 2001 Mar 02; 276(9):6350-8. PMID: 11078737.
    View in: PubMed
  44. Whetstine JR, Yueh MF, McCarver DG, Williams DE, Park CS, Kang JH, Cha YN, Dolphin CT, Shephard EA, Phillips IR, Hines RN. Ethnic differences in human flavin-containing monooxygenase 2 (FMO2) polymorphisms: detection of expressed protein in African-Americans. Toxicol Appl Pharmacol. 2000 Nov 01; 168(3):216-24. PMID: 11042094.
    View in: PubMed
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