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Saghi Ghaffari

  • ASSOCIATE PROFESSOR Developmental and Regenerative Biology
  • ASSOCIATE PROFESSOR Medicine
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Education

  • M.D., Universite de Paris XII, Paris, France

  • MSc., Universite de Paris XII, Paris, France

  • Clinical Scientist, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology

  • Ph.D., University of British Columbia, Vancouver, B.C., Canada

Awards

  • 2011 -
    Myeloproliferative Neoplams
    Research Foundation New Investigator Award

  • 2008 -
    Roche Foundation for Anemia Research (RoFAR) Award

  • 2008 -
    Irma Hirschl/Weill-Caulier Trust Research Award

  • 2007 -
    Black Family Stem Cell Institute Exploratory Research Award

  • 2006 -
    Research Scholar
    American Cancer Society

  • 1998 -
    NIH Mentored Clinician Scientist Career Award
    National Cancer Institute

  • 1991 - 1995
    Terry Fox Physician-Scientist Fellowship
    National Cancer Institute of Canada

Research

My Laboratory is focused on elucidating signals that regulate transcriptional programs of stem cell fate decisions and mechanisms of alterations of these in disease.

Stem cells have a unique and remarkable property in that a single cell can   regenerate the entire tissue (somatic) or all tissues in the whole body   (embryonic). A central focus of my laboratory is to dissect molecular   mechanisms that regulate stem cell fate with critical implications for   understanding and treatment of human disease. We work with both   embryonic stem (ES) cells and adult hematopoietic (blood) stem cells and   use transgenic and knock out mouse models. Located in hypoxic niches,   adult hematopoietic stem cells are mostly quiescent whereas embryonic   stem cells are highly proliferative. We   have identified distinct members of Forkhead FoxO family of   transcription factors as critical regulators of stem cell activity in   adult hematopoietic and in embryonic stem cells. FoxO factors are bona fide tumor suppressors with key functions in the regulation of longevity and metabolism. The targets of FoxO   in stem cells that we have identified are key regulators of   pluripotency of (ES) or of quiescence and genomic stability of (adult)   stem cells. Our current work involves investigating the metabolic   regulation and function of FoxO in normal and cancer stem cells. These   investigations should generate information that can be exploited for   improving the expansion of normal stem cells for therapy and for the   specific targeting of cancer stem cells.   

Red blood cells carry oxygen to all tissues in the body and the alteration in their production or maturation causes disorders such as b-thalassemia and sickle cell anemia.  Another   focus of my laboratory has been to elucidate signaling pathways that   control the production and maturation of red blood cells. Work in the   laboratory has found important functions for AKT signaling pathway in   these processes. Using genetic approaches we are addressing the function   of AKT phosphorylation of its downstream targets GATA-1 and Foxo3 in vivo.  Our unpublished results indicate that this pathway might be exploited for the treatment of some human erythroid disorders.

We have recently identified a novel regulator of human ES cell pluripotency. The potential of this factor in improving the efficiency of generation of induced pluripotent stem (iPS) cells is being currently tested in the laboratory.

Using,   genetic, biochemical and molecular approaches my laboratory is   investigating questions related to stem and progenitor cell fate. In   carrying this work forward we have set up multiple collaborations with   investigators at Mount Sinai and elsewhere. Several projects deriving   from the line of work described here are available to PhD and MD/PhD   students at Mount Sinai.

Current members

Xin Zhang M.D.-Ph.D., Post-doctoral Fellow

Pauline Rimmelé Ph.D., Post-doctoral Fellow

Valentina D’Escamard, MSc., Laboratory Manager

Carolina Bigarella Ph.D., Post-doctoral Fellow

Genís Campreciós Ph.D., Post-doctoral Fellow

Jose Luis Garrido, MSc., Associate Researcher

Brigitte Izac, MSc., Visiting Researcher (INSERM Paris)

Sébastien Lofek,  Visiting Student (Université de Paris VII)

Adithya Sarveswaran, High School Student in Training

Publications

Zhang X, Yalcin S, Lee DF, Lee S, Yeh T, Jie S, Kennedy M, Sellers R, Landthaler M, Tuschl T, Chi NW, Lemischka I, Keller G, Ghaffari S. FOXO1 is an essential regulator of pluripotency in human embryonic stem cells. Nature Cell Biology 2011 July;: doi:10.1038/ncb2293.

Yalcin S, Marinkovic D, Mungamuri S, Tong W, Ghaffari S. Oxidative stress-mediated amplification of AKT/mTOR signaling pathway leads to myeloproliferative syndrome in Foxo3-/- mice . EMBO Journal 2010 Nov 26; 29(24): 4118-31.

Yu D , dos Santos CO, Zhao G, Jiang J, Amigo JD, Khandros E , Dore LC, Yao Y, D'Souza J, Ghaffari S, Choi J, Friend S, Tong W, Orange JS, Paw BH, Weiss MJ. miR-451 Protects Against Erythroid Oxidant Stress by Repressing 14-3-3z.. Genes & Development 2010; 24(15): 1620-1633.

Zhang X, Rielland M, Yalcin S, Ghaffari S. Regulation and function of FoxO transcription factors in normal and cancer cells. What have we learned?. Current Drug Targets [Epub ahead of print] 2011 Mar 28;.

Shazib P, Ghaffari S, Taneja R. Oxidative Stress Regulation of Stem and Progenitor Cells. Forum Issue Antioxidants & Redox Signaling 2009; 11(11): 2777-2789.

Yalcin S, Chung TK, Vercherat C, Gulbagci J, Gopinadhan S, Taneja R, Ghaffari S. Stra13 Regulates oxidative stress mediated skeletal muscle degeneration. Hum Mol Genet 2009; 18(22): 4304-4316.

Yalcin S, Zhang X, Marinkovic D, Luciano J, Sarkar A, Ghaffari C, Vercherat C, Taneja R, Ghaffari S. Foxo3 is essential for the regulation of ATM and oxidative stress-mediated homeostasis of hematopoietic stem cells. Journal of Biological Chemistry 2008; 283: 25692-25705.

Ghaffari S. Oxidative stress in the regulation of normal and neoplastic hematopoiesis. Forum Issue Antioxidants & Redox Signaling 2008; 10: 1923-1940.

Marinkovic D, Zhang X, Yalcin S, Brugnara C, Huber T, Ghaffari S, . Foxo3 is required for the regulation of oxidative stress in erythropoiesis. Journal of Clinical Investigation (This paper was highlighted in Conmentary: JCI (8): 2075-2077, 2077). 2007; 117(8): 2133-2144.

Zhao W, Kitidis C, Fleming MD, Lodish HF, Ghaffari S , . Erythropoietin stimulates phosphorylation and activation of GATA-1 via the PI3-kinase-AKT signaling pathway. Blood (this paper was highlighted in Inside Blood; 107 (3): 851-85) 2006; 107(3): 907-915.

Ghaffari S, Kitidis C, Zhao W, Marinkovic D, Fleming MD, Luo B, Marszalek J, Lodish HF. AKT induces erythroid-cell maturation of JAK2-deficient fetal liver progenitor cells and is required for Epo regulation of erythroid-cell differentiation. Blood Mar 1; 107(5): 1888-91.

Ghaffari S, Jagani Z, Kitidis C, Lodish HF, Khosravi-Far R. Cytokines and BCR-ABL mediate suppression of TRAIL-induced apoptosis through inhibition of forkhead FOXO3a transcription factor. Proc Natl Acad Sci U S A 2003; 100(11): 6523-6528.

Steen H, Fernandez M, Ghaffari S, Pandey A, Mann M. Phosphotyrosine mapping in oncogenic BCR-ABL using phosphotyrosine-specific immonium ion scanning. Molecular Cell Proteomics 2003 Mar; 2(3): 138-45.

Zhao X, Ghaffari S, Lodish HF, Malashkevich VN, Kim PS. Stucture of the BCR-ABL oncoprotein oligomerization domain. Nature Structural Biology 2002 ; 9(2): 1-4 .

Industry Relationships

Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.

Dr. Ghaffari did not report having any of the following types of financial relationships with industry during 2012 and/or 2013: consulting, scientific advisory board, industry-sponsored lectures, service on Board of Directors, participation on industry-sponsored committees, equity ownership valued at greater than 5% of a publicly traded company or any value in a privately held company. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.

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