Saghi Ghaffari

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  Our unpublished results indicate that this pathway might be exploited for the treatment of some human erythroid disorders.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