Photo of Johnathan Whetstine,  PhD

Johnathan Whetstine, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 643-4374


jwhetstine@hms.harvard.edu

Johnathan Whetstine, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Medicine, Harvard Medical School
  • Associate Geneticist, Medicine, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The Whetstine laboratory is interested in understanding how the chromatin microenvironment regulates gene expression while maintaining a stable genome. Our ultimate goal is to harness this mechanistic understanding to identify novel therapeutic opportunities and to block chemotherapeutic resistance. We integrate biochemistry, genetics, genomics and computation to elucidate chromatin modulators involved in these processes. We have initiated these types of studies by focusing on a specific class of chromatin regulators, the JmjC-containing histone demethylases. Since the discovery of these chromatin regulators, my laboratory has started screening tumors for genomic anomalies (copy changes and mutations) in this class of enzyme and examining their molecular roles at a biochemical, molecular and in vivo level. These combined approaches will determine whether tumors with alterations in JmjC enzymes provide an opportunity to modify conventional chemotherapy and identify novel molecular diagnostics.

Publications

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  • Black JC, Zhang H, Kim J, Getz G, Whetstine JR. Regulation of Transient Site-specific Copy Gain by MicroRNA. J Biol Chem 2016; 291:4862-71. PubMed
  • Black JC, Whetstine JR. RNF2 E3 or Not to E3: Dual Roles of RNF2 Overexpression in Melanoma. 2015; 5:1241-3. PubMed
  • Black JC, Whetstine JR. Too little O2 Too much gain. Cell Cycle 2015. PubMed
  • 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; 29:1018-31. PubMed
  • 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. 2015; 5:255-63. PubMed
  • 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. 2015; 5:245-54. PubMed
  • 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; 6:8257. PubMed
  • Van Rechem C, Whetstine JR. Examining the impact of gene variants on histone lysine methylation. Biochim Biophys Acta 2014; 1839:1463-76. PubMed
  • Whetstine JR. Methylation: a multifaceted modification - looking at transcription and beyond. Biochim Biophys Acta 2014; 1839:1351-2. PubMed
  • 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; 154:541-55. PubMed
  • Black JC, Whetstine JR. Tipping the lysine methylation balance in disease. 2012; 99:127-35. PubMed
  • Black JC, Van Rechem C, Whetstine JR. Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell 2012; 48:491-507. PubMed
  • 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; 286:30462-70. PubMed
  • Black JC, Whetstine JR. Chromatin landscape: methylation beyond transcription. Epigenetics 2011; 6:9-15. PubMed
  • 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粒 during cell cycle progression. Mol Cell 2010; 40:736-48. PubMed
  • 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; 11:1376-82. PubMed
  • 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; 449:689-94. PubMed
  • 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; 128:1077-88. PubMed
  • 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; 125:467-81. PubMed
  • 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; 18:483-90. PubMed
  • 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; 119:941-53. PubMed
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