Emmanuelle Passegué, PhD

Academic Appointments

  • Alumni Professor of Genetics and Development(in Rehabilitation and Regenerative Medicine)

Current Administrative Positions

  • Director, Columbia Stem Cell Initiative
Emmanuelle Passegué, PhD

Dr. Emmanuelle Passegué, Ph.D. is the Alumni Professor of Genetics & Development and the Director of the Columbia Stem Cell Initiative (CSCI) at Columbia University Irving Medical Center (CUIMC) in New York City. Dr. Passegué received her Ph.D. from the University Paris XI (France), and trained with Dr. Erwin Wagner (Institute for Molecular pathology, Vienna, Austria) and Dr. Irv Weissman (Stanford University, USA) before joining the University of California San Francisco (UCSF) in 2005. Dr. Passegué was a Professor of Medicine in the Hematology/Oncology Division and the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at UCSF until 2016 before joining CUIMC in January 2017. Her research investigates the biology of blood-forming hematopoietic stem cells in normal and deregulated contexts such as hematological malignancies and physiological aging. Dr. Passegué has received a number of awards and prizes including a Scholar Award from the Lymphoma and Leukemia Society, an Outstanding Investigator Award from the NHLBI, and the 2019 William Dameshek Prize from the American Society of Hematology.

Our laboratory studies how hematopoietic stem cells (HSC) regulate blood production during the lifetime of an ever-changing organism. This fundamental question is central to tissue development, maintenance and regeneration, and has implications for every aspect of adult physiology ranging from response to stress, development of diseases, and biology of aging. We are interested in identifying the mechanisms that control HSC activity in normal and a range of deregulated conditions, with the goal of identifying affected genes and pathways that could be used to develop new therapies to treat human myeloid malignancies and help combat physiological aging. Towards this end, we are employing a variety of cross-disciplinary approaches using mouse models and human samples.

Hematopoiesis & Hematopoietic Stem Cell Biology

Departments and Divisions

  • Department of Genetics & Development

Languages Spoken

  • French

Centers / Institutes / Programs

  • Columbia Stem Cell Initiative

Past Positions

2014 - 2016, Professor, Department of Medicine, Division of Hematology/Oncology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA

2010 - 2014, Associate Professor (with tenure), Department of Medicine, Division of Hematology/Oncology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA

2006 - 2010, Assistant Professor, Department of Medicine, Division of Hematology/Oncology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA

2001 - 2005, Postdoctoral Fellow, Department of Pathology, Stanford University, Stanford, CA. Advisor: Dr. Irv. Weissman

1996 - 2000, Postdoctoral Fellow, Institute of Molecular Pathology (IMP), Vienna, Austria. Advisor: Dr. Erwin Wagner

Honors and Awards

2019 -William Dameshek Prize, American Society of Hematology (ASH)

2017 - NHLBI Outstanding Investigator Award

2014 - Glenn Award for Research on the Biological Mechanisms of Aging

2014 - McCulloch and Till Lectureship Award (ISEH)

2012 - Leukemia and Lymphoma Society (LLS) Scholar Award

2009 - California Institute of Regenerative Medicine (CIRM) New Faculty Award

2008 - Rita Allen Scholar Award

2007 - American Society of Hematology (ASH) Scholar Award

Research Interests

  • Hematopoietic stem cell biology
  • Myeloid malignancies
  • Stem cells in tissue homeostasis and aging

NIH Grants

  • AUTOPHAGY ENGAGEMENT AND HEMATOPOIETIC STEM CELL MAINTENANCE DURING AGING (Federal Gov)

    Jan 1 2020 - Dec 31 2023

    EMERGENCY MYELOPOIESIS PATHWAYS IN THE CONTROL OF BLOOD PRODUCTION (Federal Gov)

    Dec 1 2016 - Nov 30 2023

    AUTOPHAGY AND HEMATOPOIETIC STEM CELL FUNCTION IN AGING AND LEUKEMIA (Private)

    Jul 1 2019 - Jun 30 2021

    LEUKEMIA & LYMPHOMA SOCIETY CAREER DEVELOPMENT PROGRAM (Private)

    Jul 1 2017 - Jun 30 2019

    ROLE OF AUTOPHAGY IN NORMAL AND TRANSFORMED HEMATOPOIETIC STEM CELLS (Federal Gov)

    Apr 1 2017 - Mar 31 2019

    ROLE OF AUTOPHAGY IN NORMAL AND TRANSFORMED HEMATOPOIETIC STEM CELLS (Federal Gov)

    Apr 1 2017 - Mar 31 2019

    PLATELET AND MEGAKARYOCYTE BIOLOGY IN THE NORMAL AND INJURED LUNG (Federal Gov)

    Jul 1 2017 - Apr 30 2018

    LEUKEMIA AND LYMPHOMA SOCIETY GRANT AGREEMENT (Private)

    Jan 1 2017 - Jun 30 2017

Lab Projects

  • Manipulating Emergency Myelopoiesis Pathways to Treat Blood Deregulations

    Blood production is a highly regulated process that tailors the output of the myeloid and lymphoid lineages based on hematopoietic demands and the needs of the organism. While the overall structure of the blood system and its hierarchical nature is well established, many questions still remain regarding the mechanisms controlling self-renewal activity and quiescent status of HSCs, and the lineage specifications that occur in non-self-renewing multipotent progenitors (MPP). Our investigations of emergency myelopoiesis pathways have provided new insights into the mechanisms of HSC activation and lineage commitment, and showed that a shift from glycolysis to mitochondrial metabolism changes the epigenetic landscape of activated HSCs and drives lineage poising. They also uncovered new regulatory mechanisms by showing that environmental factors produced by the bone marrow (BM) niche dictate the production of various lineage-biased multipotent progenitors and control the local expansion and differentiation of committed progenitor cells. These mechanisms normally tailor blood production to the need of the organism, but are hijacked in malignancies. Our goal is to explore the role of these mechanisms in various deregulated contexts, and to manipulate them for the treatment of blood malignancies and immune deregulations.

  • Fighting Blood Aging by Preventing HSC Decline

    The blood system is essential for organismal health and to maintain the body's ability to fight infections. HSCs self-renew and maintain blood production for life and, as such, are one of the few blood cells that truly age or initiate malignancies. While HSCs efficiently produce all mature blood cells in young individuals, they often fail with age leading to degraded blood production characterized by anemia, immunosenescence, blood cancers, and clonal hematopoiesis, which is a new contributing factor to systemic age-related organ dysfunction. Paradoxically, although HSCs numerically expand with age, their functional activity declines over time, resulting in impaired engraftment and decreased blood regeneration capacity. Our recent work on aged HSCs has identified novel molecular hallmarks of an old state, and provided unique insights into the mechanisms of stem cell aging. In particular, it showed that replication stress as a potent driver of functional exhaustion of aged HSCs, and demonstrated that defective activation of autophagy allowed the accumulation of metabolically overactivated and dysfunctional old HSCs. Our goal is to extend these investigations to develop novel rejuvenation interventions for healthier aging, which include restoring the elderly's ability to fight infections and to combat the development of blood cancers.

Lab Members

  • Masayuki Yamashita, MD, PhD, Postdoctoral Research Fellow
  • Evgenia Verovskaya, PhD, Postdoctoral Research Fellow
  • Amélie Collins, MD, PhD, Postdoctoral Research Fellow
  • Theodore Ho, PhD Graduate Student (UCSF)
  • Nathan Edwards, PhD Graduate Student (UCSF)
  • Paul Dellorusso, PhD Graduate Student
  • Gloria Perez, DVM, PhD, Laboratory Manager
  • Yoon A Kang, PhD, Postdoctoral Research Fellow
  • Chang Yoon Moon, Undergraduate Student

Publications

Yamashita M, Dellorusso PV, Olson OC,Passegué E.Dysregulated haematopoietic stem cell behaviour in myeloid leukaemogenesis(link is external and opens in a new window).Nat Rev Cancer. 2020 May 15. doi: 10.1038/s41568-020-0260-3. Online ahead of print.PMID:32415283Review.

Olson OC, Kang YA,Passegué E.Normal Hematopoiesis Is a Balancing Act of Self-Renewal and Regeneration(link is external and opens in a new window).Cold Spring Harb Perspect Med. 2020 Jan 27:a035519. doi: 10.1101/cshperspect.a035519. Online ahead of print.PMID:31988205

Kang YA, Pietras EM,Passegué E.Deregulated Notch and Wnt signaling activates early-stage myeloid regeneration pathways in leukemia.(link is external and opens in a new window)J Exp Med. 2020 Mar 2;217(3):jem.20190787. doi: 10.1084/jem.20190787.PMID:31886826

Cable J, Fuchs E, Weissman I, Jasper H, Glass D, Rando TA, Blau H, Debnath S, Oliva A, Park S, Passegué E, Kim C, Krasnow MA.Ann.Adult stem cells and regenerative medicine-a symposium report(link is external and opens in a new window).N Y Acad Sci. 2020 Feb;1462(1):27-36. doi: 10.1111/nyas.14243. Epub 2019 Oct 26.PMID:31655007Free PMC article.

Yamashita M and Passegué E.TNF-a Coordinates Hematopoietic Stem Cell Survival and Myeloid Regeneration.(link is external and opens in a new window)Cell Stem Cell 25, 1-16 2019 September

Verovskaya E, Dellorusso P, and Passegué E.Losing Sense of Self and Surroundings: Hematopoietic Stem Cell Aging and Leukemic Transformation.Trends in Molecular Medicine. 25 (6): 494-515, 2019 June.

Gaillard C, Surianarayanan S, Bentley T, Warr MR, Fitch B, Geng H, Passegué E, de Thé H, Kogan SC. Identification of IRF8 as a potent tumor suppressor in murine acute promyelocytic leukemia. Blood Adv., 2(19):2462-2466, 2018.

Leeman DS, Hebestreit K, Ruetz T, Webb AE, McKay A, Pollina EA, Dulken BW, Zhao X, Yeo RW, Ho TT, Mahmoudi S, Devarajan K, Passegué E, Rando TA, Frydman J, Brunet A. Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging. Science, 359:1277-1283, 2018.

Hérault A, Binnewies M, Leong S, Calero-Nieto FJ, Zhang SY, Kang Y-A, Wang X, Pietras E, Chu SH, Barry-Holson K, Armstrong S, Göttgens B, Passegué E. Myeloid progenitor cluster formation drives emergency and leukemic myelopoiesis.Nature, 544:53-58, 2017.

Ho TT, Warr MR, Adelman E, Lansinger O, Flach J, Verovskaya E, Figueroa ME, Passegué E. Autophagy maintains metabolism and functional activity of a subset of aged hematopoietic stem cells. Nature, 543:205-210, 2017.

Pietras M, Mirantes-Barbeito C, Fong S, Loeffler D, Kovtonyuk LV, Zhang SY, Lakshminarasimhan R, Chin CP, Techner J-M, Will B, Nerlov C, Steidl U, Manz MG, Schroeder T, Passegué E. Interleukin-1 drives hematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal. Nat Cell Biol, 18:607-618, 2016.

Pietras E*, Reynaud D*, Carlin D, Calero-Nieto FJ, Kang YA, Leavitt AD, Stuart JM, Göttgens B, Passegué E. Functionally distinct subsets of lineage-biased multipotent progenitors control blood production in normal and regenerative conditions. Cell Stem Cell, 17:35-46, 2015. (*equal contribution)

Flach J, Bakker ST, Mohrin M, Conroy PC, Pietras EM, Reynaud D, Alvarez S, Diolaiti ME, Ugarte F, Forsberg EC, Le Beau MM, Stohr BA, Méndez J, Morrison CG, Passegué E. Replication stress is a potent driver of functional decline in aging hematopoietic stem cells. Nature, 512:198-202, 2014.

Pietras EM, Lakshminarasimhan R, Techner JM, Fong S, Flach J, Binnewies M, Passegué E. Re-entry into quiescence protects hematopoietic stem cells from the killing effect of chronic exposure to type I interferons.J Exp Med, 211:245-262, 2014.

Schepers K, Pietras EM, Reynaud D, Flach J, Binnewies M, Garg T, Wagers AJ, Hsiao EC, Passegué E. Myeloproliferative neoplasia remodels the endosteal bone marrow niche into a self-reinforcing leukemic niche. Cell Stem Cell, 13:285-299, 2013.

Warr MR, Binnewies M, Flach J, Reynaud D, Garg T, Malhotra R, Debnath J, Passegué E. FOXO3A directs a protective autophagy program in haematopoietic stem cells.Nature, 494:323-327, 2013.

Reynaud D, Pietras EM, Barry-Holson K, Mir A, Binnewies M, Jeanne M, Sala-Torra O, Radich JP, Passegué E. IL-6 controls leukemic multipotent progenitor cell fate and contributes to chronic myelogenous leukemia development. Cancer Cell, 20:661-673, 2011.

Mohrin M, Bourke E, Alexander D, Warr M, Barry-Holson K, LeBeau M, Morrison CG, Passegué E. Hematopoietic stem cell quiescence promotes error prone DNA repair and mutagenesis.Cell Stem Cell, 7:174-485, 2010.

For a complete list of publications, please visit PubMed.gov