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Hock Lab

Research topics include: transcription factors in blood development and leukemia

Hanno Hock, MD, PhD
Assistant Professor of Medicine
Harvard Medical School

Research Summary

The Hock laboratory explores the molecular basis of blood cell formation and the pathogenesis of leukemia and lymphoma. Specifically, we study the transcription factors that regulate gene activity during normal blood cell development and how the transcriptional apparatus goes awry in cancer. For example, we have developed important insights into a network of transcription factors that help maintain blood stem cells in the bone marrow; this work could lead to new strategies for increasing the yield of stem cells for bone marrow transplantation. Another project in our laboratory focuses on deciphering the multistep process that leads to lymphoblastic leukemia of childhood, with the goal of identifying new drug targets for this devastating disease.  Finally, we are interested in how DNA packaging affects the interaction between genes and transcription factors, especially with regard to oncogenes and tumor suppressor genes important in human cancer.

 

Read the Hock Lab's Annual Report in Full

Hanno Hock, MD, PhD
Principal Investigator
Group Members

  • Adlen Foudi, PhD
  • Hanno Hock, MD, PhD 
  • Daniel Kramer
  • Ondrej Krejci, PhD  
  • Jinzhong Qin, PhD

Research Preojects

Our laboratory is interested in the molecular control of normal and malignant stem cells with an emphasis on the hematopoietic system. Blood cells need to be continuously replenished by 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 leukemia and lymphoma cells. As HSCs mature, they undergo successive changes in gene expression. The transcriptional apparatus must ensure that genes specific to immature cells are repressed as differentiation proceeds while genes that are necessary for mature cells become activated. This activating and inactivating of genes is achieved by cooperative action of a variety of lineage-specific and general transcription factors and the complex molecular machinery that regulates the accessibility of different regions of the genome in chromatin. We investigate how transcription factors establish differentiation-specific transcriptional programs and how such programs can become derailed in cancer, leukemia and lymphoma.

Transcriptional control of normal and malignant hematopoietic stem cells in the adult bone marrowHock Lab Research
Hematopoiesis in the bone marrow emanates HSCs. We are studying the basic biology of HSCs. Specifically we explore how a network of transcription factors that includes Tel-Etv6, Gfi1, Gfi1b and Gata2 maintains HSCs in the bone marrow (Hock et al. 2004, Genes & Development; Hock et al. 2004, Nature). The goal is to exploit the biology of transcriptional regulation of HSCs to maintain, expand, and possibly even generate HSCs ex vivo so that more patients will have the option of bone marrow transplantation. In a closely related effort, we are exploring the molecular programs of stem cells in leukemia and lymphoma to identify differences in their molecular regulation compared with normal HSCs. Such differences may allow us to specifically target tumor stem cells while sparing normal blood formation.

Deciphering the molecular events leading to acute lymphoblastic leukemia of childhood
About one in 2000 children develop this catastrophic illness, most often with a t(12;21) translocation. Despite very aggressive treatments, not all children can be cured, and some suffer from long-term side effects of their therapy. Rational development of more specific, less toxic treatments requires a precise understanding of the molecular mechanisms that cause the disease. We have discovered that TEL-AML1, the first hit in childhood leukemia, generates a preleukemic, latent lesion in HSCs. We are now exploring how additional genetic hits cooperate to derail normal blood development and generate leukemia. Deciphering the multistep pathogenesis of this entity is likely to serve as a paradigm for the development of other malignant diseases.

Exploration of novel epigenetic regulators in stem cells
Our understanding of how specialized cells of the body establish their identity by regulating access to genes continues to increase. For example, a large fraction of the genes active in brain cells are inactive in blood cells and, therefore, are stored in a very dense, inaccessible state. As a large number of new molecules involved in the regulation of gene accessibility have only recently been identified, their manipulation provides unique opportunities for the development of entirely novel therapies. Our laboratory is investigating the utility of a novel group of proteins termed MBT-proteins, which is very important in condensing DNA and modifying histones, the molecules. Evidence suggests that this protein family may play important roles in hematopoiesis and hematologic malignancy, but its precise functions remains very poorly understood. Our laboratory has recently discovered entirely novel functions of MBT-domain proteins in stem cells.

Research Positions

Postdoctoral Research Fellow (1)

A postdoctoral Research Fellow position is available in the laboratory of Hanno Hock, MD, PhD, Massachusetts General Hospital, Harvard Medical School, for studying the transcriptional regulation of stem cells in normal hematopoiesis and leukemia using genetically engineered mice. The laboratory is located in the new Simches Research Building at the main campus of the Massachusetts General Hospital. The fellow will have simultaneous appointments at the Cancer Center and Center for Regenerative Medicine of MGH and Harvard Medical School and will be affiliated with the Harvard Stem Cell Institute. Candidates are expected to have completed their PhD and/or MD degree (with significant prior research experience) and be highly motivated for a career in academic biomedical research.

Contact:

Please email a brief cover letter and CV to:

Hanno Hock, MD, PhD
Assistant Professor of Medicine
Massachusetts General Hospital
Harvard Medical School
Simches Research Building, CPZN 4200, 4th floor
Boston, MA 02114
E-mail: Hock.Hanno@mgh.harvard.edu

Hock Laboratory

185 Cambridge Street
Simches Bldg, CPZN 4200, 4th floor
Boston, MA 02129

Phone: 617-643-3145
Email: hhock@partners.org

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