Photo of Christopher Ott,  PhD

Christopher Ott, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (312) 953-3436


christopher.ott@mgh.harvard.edu

Christopher Ott, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Instructor, Medicine, Harvard Medical School
  • Instructor, Center for Cancer Research, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Mutations in cancer cells lead to malfunctioning control of gene expression. Our laboratory is dedicated to discovering the gene expression control factors that are essential for leukemia and lymphoma cell survival. Discovery of these factors prompts further efforts in our group to design chemical strategies for the synthesis and deployment of prototype drugs targeting the aberrant mechanisms of gene control. Biologically, gene control factors represent compelling therapeutic targets for these cancers, as they are master regulators of cell identity. Yet despite this clear rationale, most are perceived as intractable drug targets owing to their large size, disordered shapes, and involvement in complex cellular circuits. Recent advances in gene editing technologies and discovery chemistry have advanced our capability to rapidly identify targetable aspects of gene control and methods to disrupt their function. We use these genetic and chemical tools to probe cancer cell circuitry and inform therapeutic hypotheses.

Publications

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  • Ott CJ, Wu CJ. HDAC Inhibitors Finally Open Up: Chromatin Accessibility Signatures of CTCL. Cancer Cell 2017; 32:1-3. PubMed
  • Winter GE, Mayer A, Buckley DL, Erb MA, Roderick JE, Vittori S, Reyes JM, di Iulio J, Souza A, Ott CJ, Roberts JM, Zeid R, Scott TG, Paulk J, Lachance K, Olson CM, Dastjerdi S, Bauer S, Lin CY, Gray NS, Kelliher MA, Churchman LS, Bradner JE. BET Bromodomain Proteins Function as Master Transcription Elongation Factors Independent of CDK9 Recruitment. Mol Cell 2017. PubMed
  • Shortt J, Ott CJ, Johnstone RW, Bradner JE. A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer 2017; 17:268. PubMed
  • Hogg SJ, Vervoort SJ, Deswal S, Ott CJ, Li J, Cluse LA, Beavis PA, Darcy PK, Martin BP, Spencer A, Traunbauer AK, Sadovnik I, Bauer K, Valent P, Bradner JE, Zuber J, Shortt J, Johnstone RW. BET-Bromodomain Inhibitors Engage the Host Immune System and Regulate Expression of the Immune Checkpoint Ligand PD-L1. Cell Rep 2017; 18:2162-2174. PubMed
  • Koblan LW, Buckley DL, Ott CJ, Fitzgerald ME, Ember SW, Zhu JY, Liu S, Roberts JM, Remillard D, Vittori S, Zhang W, Schonbrunn E, Bradner JE. Assessment of Bromodomain Target Engagement by a Series of BI2536 Analogues with Miniaturized BET-BRET. ChemMedChem 2016; 11:2575-2581. PubMed
  • Koo SJ, Fernández-Montalván AE, Badock V, Ott CJ, Holton SJ, von Ahsen O, Toedling J, Vittori S, Bradner JE, Gorjánácz M. ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication. 2016. PubMed
  • Viny AD, Ott CJ, Spitzer B, Rivas M, Meydan C, Papalexi E, Yelin D, Shank K, Reyes J, Chiu A, Romin Y, Boyko V, Thota S, Maciejewski JP, Melnick A, Bradner JE, Levine RL. Dose-dependent role of the cohesin complex in normal and malignant hematopoiesis. J Exp Med 2015; 212:1819-32. PubMed
  • Knoechel B, Roderick JE, Williamson KE, Zhu J, Lohr JG, Cotton MJ, Gillespie SM, Fernandez D, Ku M, Wang H, Piccioni F, Silver SJ, Jain M, Pearson D, Kluk MJ, Ott CJ, Shultz LD, Brehm MA, Greiner DL, Gutierrez A, Stegmaier K, Kung AL, Root DE, Bradner JE, Aster JC, Kelliher MA, Bernstein BE. An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia. Nat Genet 2014; 46:364-70. 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
  • Yigit E, Bischof JM, Zhang Z, Ott CJ, Kerschner JL, Leir SH, Buitrago-Delgado E, Zhang Q, Wang JP, Widom J, Harris A. Nucleosome mapping across the CFTR locus identifies novel regulatory factors. Nucleic Acids Res 2013; 41:2857-68. PubMed
  • Ott CJ, Kopp N, Bird L, Paranal RM, Qi J, Bowman T, Rodig SJ, Kung AL, Bradner JE, Weinstock DM. BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood 2012; 120:2843-52. PubMed
  • Zhang Z, Ott CJ, Lewandowska MA, Leir SH, Harris A. Molecular mechanisms controlling CFTR gene expression in the airway. J Cell Mol Med 2012; 16:1321-30. PubMed
  • Bischof JM, Ott CJ, Leir SH, Gosalia N, Song L, London D, Furey TS, Cotton CU, Crawford GE, Harris A. A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function. Thorax 2012; 67:385-91. PubMed
  • Ott CJ, Bischof JM, Unti KM, Gillen AE, Leir SH, Harris A. Nucleosome occupancy reveals regulatory elements of the CFTR promoter. Nucleic Acids Res 2012; 40:625-37. PubMed
  • Ott CJ, Harris A. Genomic approaches to studying CFTR transcriptional regulation. Methods Mol Biol 2011; 741:193-209. PubMed
  • Ott CJ, Blackledge NP, Kerschner JL, Leir SH, Crawford GE, Cotton CU, Harris A. Intronic enhancers coordinate epithelial-specific looping of the active CFTR locus. Proc Natl Acad Sci U S A 2009; 106:19934-9. PubMed
  • Ott CJ, Blackledge NP, Leir SH, Harris A. Novel regulatory mechanisms for the CFTR gene. Biochem Soc Trans 2009; 37:843-8. PubMed
  • Chen Y, Ott CJ, Townsend K, Subbaiah P, Aiyar A, Miller WM. Cholesterol Supplementation During Production Increases the Infectivity of Retroviral and Lentiviral Vectors Pseudotyped with the Vesicular Stomatitis Virus Glycoprotein (VSV-G). Biochem. Eng. J. 2011; 44:199-207. PubMed
  • Ott CJ, Suszko M, Blackledge NP, Wright JE, Crawford GE, Harris A. A complex intronic enhancer regulates expression of the CFTR gene by direct interaction with the promoter. J Cell Mol Med 2009; 13:680-92. PubMed
  • Ott CJ, Harris A. Genomic approaches for the discovery of CFTR regulatory elements. Transcr 2012; 2:23-7. PubMed
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