Photo of Hanno R. Hock,  MD, PhD

Hanno R. Hock, MD, PhD

Massachusetts General Hospital

Massachusetts General Hospital


Hhock@partners.org

Hanno R. Hock, MD, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Medicine, Harvard Medical School
  • Assistant Professor of Medicine, CANCER CENTER, Massachusetts General Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our laboratory is interested in the transcriptional regulation of normal blood cell development and leukemia. All blood cells arise from a small population of hematopoietic stem cells (HSCs) that have the capacity to, both, self-renew and mature stepwise into all known blood lineages. HSCs are also the ancestors of leukemic cells. As HSCs mature, they undergo successive changes in gene expression that are orchestrated by transcription factors. The transcriptional apparatus must ensure that genes specific to immature cells are repressed as differentiation proceeds while genes necessary for the function of mature blood cells become activated. This is achieved by co-operative action of a variety of lineage specific and general transcription factors. Individual transcription factors function in a highly context sensitive manner, so that in some cases the same transcription factor may even have opposite roles in different lineages. Using genetically engineered mouse strains, we investigate how key transcription factors establish differentiation specific transcriptional programs and how abnormal transcription factors derail this process to allow for the development leukemia. Our major emphasis is on three transcription factors: the Ets-related transcription factor Tel/Etv6 and the zinc-finger transcription factor Gfi-1, both critical for maintaining HSCs in the bone marrow, and the leukemia translocation-associated hybrid transcription factor Tel-Aml1.

Publications

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  • Shen EY, Jiang Y, Mao W, Futai K, Hock H, Akbarian S. Cognition and mood-related behaviors in l3mbtl1 null mutant mice. PLoS ONE 2015; 10:e0121252. PubMed
  • Foudi A, Kramer DJ, Qin J, Ye D, Behlich AS, Mordecai S, Preffer FI, Amzallag A, Ramaswamy S, Hochedlinger K, Orkin SH, Hock H. Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation. J Exp Med 2014. PubMed
  • Shi LZ, Kalupahana NS, Turnis ME, Neale G, Hock H, Vignali DA, Chi H. Inhibitory role of the transcription repressor Gfi1 in the generation of thymus-derived regulatory T cells. Proc Natl Acad Sci U S A 2013; 110:E3198-205. PubMed
  • Qin J, Whyte WA, Anderssen E, Apostolou E, Chen HH, Akbarian S, Bronson RT, Hochedlinger K, Ramaswamy S, Young RA, Hock H. The polycomb group protein L3mbtl2 assembles an atypical PRC1-family complex that is essential in pluripotent stem cells and early development. Cell Stem Cell 2012; 11:319-32. PubMed
  • Qin J, Van Buren D, Huang HS, Zhong L, Mostoslavsky R, Akbarian S, Hock H. Chromatin protein L3MBTL1 is dispensable for development and tumor suppression in mice. J Biol Chem 2010; 285:27767-75. PubMed
  • Hock H. Some hematopoietic stem cells are more equal than others. J Exp Med 2010; 207:1127-30. PubMed
  • Monach PA, Nigrovic PA, Chen M, Hock H, Lee DM, Benoist C, Mathis D. Neutrophils in a mouse model of autoantibody-mediated arthritis: critical producers of Fc receptor gamma, the receptor for C5a, and lymphocyte function-associated antigen 1. Arthritis Rheum 2010; 62:753-64. PubMed
  • Eminli S, Foudi A, Stadtfeld M, Maherali N, Ahfeldt T, Mostoslavsky G, Hock H, Hochedlinger K. Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells. Nat Genet 2009; 41:968-76. PubMed
  • Schindler JW, Van Buren D, Foudi A, Krejci O, Qin J, Orkin SH, Hock H. TEL-AML1 corrupts hematopoietic stem cells to persist in the bone marrow and initiate leukemia. Cell Stem Cell 2009; 5:43-53. PubMed
  • Foudi A,Hochedlinger K,Van Buren D,Schindler JW,Jaenisch R,Carey V,Hock H. Analysis of histone 2B-GFP retention reveals slowly cycling hematopoietic stem cells. Nat Biotechnol 2008; 27:84-90. PubMed
  • Li Z, Tognon CE, Godinho FJ, Yasaitis L, Hock H, Herschkowitz JI, Lannon CL, Cho E, Kim SJ, Bronson RT, Perou CM, Sorensen PH, Orkin SH. ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex. Cancer Cell 2007; 12:542-58. PubMed
  • Hock H, Orkin SH. Zinc-finger transcription factor Gfi-1: versatile regulator of lymphocytes, neutrophils and hematopoietic stem cells. Curr Opin Hematol 2005; 13:1-6. PubMed
  • Hock H, Hamblen MJ, Rooke HM, Schindler JW, Saleque S, Fujiwara Y, Orkin SH. Gfi-1 restricts proliferation and preserves functional integrity of haematopoietic stem cells. Nature 2004; 431:1002-7. PubMed
  • Hock H, Meade E, Medeiros S, Schindler JW, Valk PJ, Fujiwara Y, Orkin SH. Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival. Genes Dev 2004; 18:2336-41. PubMed
  • Hock H, Hamblen MJ, Rooke HM, Traver D, Bronson RT, Cameron S, Orkin SH. Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation. Immunity 2003; 18:109-20. PubMed
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