Gender	Female
E-mail	saghi.ghaffari@mssm.edu
Education and Training	Ph.D, University of British Columbia, Vancouver, Canada
	M.S., Universite de Paris XI, Paris, France
	M.D, Universite de Paris XII, Paris, France
	Clinical Scientist, Whitehead Institute Massachusetts e for Biomedical Research, Institute of Technology
Awards	2008 Irma Hirschl/Weill-Caulier Trust Research Award
	2008 Roche Foundation for Anemia Research (RoFAR) 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

Ghaffari Laboratory

Curriculum Vitae: http://www.mountsinai.org/supporting-files/cv/ghaf...

Education and Training	Ph.D, University of British Columbia, Vancouver, Canada
	M.S., Universite de Paris XI, Paris, France
	M.D, Universite de Paris XII, Paris, France
	Clinical Scientist, Whitehead Institute Massachusetts e for Biomedical Research, Institute of Technology

The Ghaffari Laboratory is interested in understanding how transcriptional programs of cell differentiation are regulated and how these programs are altered in diseases.

To address these questions Dr. Ghaffari's laboratory uses embryonic stem (ES) cells and hematopoietic stem and progenitor cells.  Ghaffari's laboratory has identified Forkhead FoxO transcription factors as critical regulators of stem and progenitor cell fate.  FoxOs are highly evolutionary conserved proteins that comprise four members in the mammalian system (FoxO1, FoxO3, FoxO4 and FoxO6).  These factors exert critical functions in protecting cells against stress and preventing highly damaged cells from further replication consistent with a tumor suppressor function.  In response to stress, FoxO induce cell cycle arrest, repair damaged DNA, or initiate apoptosis via modulation of genes that control these processes.  studies conducted in the laboratory and others' have identified FoxO3 as an essential factor in suppressing oxidative stress in hematopoietic stem and progenitor cells.  In addition, Ghaffari's laboratory has found that FoxO3 suppression of oxidative stress is critical for maintenance of hematopoietic stem cell pool and for erythroid precursor cell differentiation, lifespan and cycling.  Their finding demonstrate that inhibition of oxygen radicals by FoxO3 in hematopoietic stem cells is mediated in part by FoxO3 regulation of expression of ATM tumor suppressor.  The laboratory's finding also supports a critical function for FoxO factors in the regulation of human ES cell pluripotency and differentiation.  Current works in the laboratory include identifying FoxOs targets, uncovering mechanisms of regulation of FoxO activity and investigating how FoxO regulation of oxidative stress participates in the control of genomic stability and fate of stem cells.  Using, genetic, biochemical and molecular approaches Ghaffari's laboratory is investigating these questions.  The work conducted in Dr. Ghaffari's laboratory is believed to generate critical information regarding normal processes that regulate stem and progenitor cell fate and how alterations of these processes will lead to malignancies and diseases.

 

Current Members
Postdoctoral Fellows
Xin Zhang, M.D., Ph.D.
Safak Yalcin, Ph.D.
Satish K. Mungamuri, Ph.D.

Stu dents
Dana Cullen

Please visit the Ghaffari Laboratory website for more information.

Shazib P, Taneja R, Ghaffari S. Oxidative Stress Regulation of Stem and Progenitor Cells [review]. Forum Issue Antioxidants & Redox Signaling 2009; In press.

Vercherat , Chung TK, Yalcin S, Gulbagci N, Gopinadhan S, Ghaffari S, Taneja R. Stra13 regulates oxidative stress mediated skeletal muscle degeneration. Hum Mol Genet 2009; Epub ahead of print.

Yalcin C, Zhang X, Marinkovic D, Luciano JP, Sarkar A, Brugnara 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 [review]. 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 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 2006 Feb 1; 107(3): 907-15.

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 2006 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 May 27; 100(11): 6523-8.

Steen H, Fernandez M, Ghaffari S, Pandey A, Mann M. Phosphotyrosine Mapping in Bcr/Abl Oncoprotein Using Phosphotyrosine-specific Immonium Ion Scanning. Mol Cell Proteomics 2003 Mar; 2(3): 138-45.

Zhao X, Ghaffari S, Lodish H, Malashkevich VN, Kim PS. Structure of the Bcr-Abl oncoprotein oligomerization domain. Nat Struct Biol 2002 Feb; 9(2): 117-20.