Blood Cells travel in the body to bring oxygen to all tissues, fight infections and stop bleeding when needed. Billions of blood cells are produced daily from a few hematopoietic (blood forming) stem cells (HSCs) lodged in the bone marrow of the adults.  This enormous capacity of hematopoietic stem cells to constantly generate blood declines gradually and derails with age. These age-related alterations are considered to be at the root of many blood disorders including malignancies. The work in the Ghaffari lab is focused on elucidating mechanisms that maintain healthy blood stem and progenitor cell formation that become defective with age causing disease. These mechanisms may be explored for therapeutic purposes and to prevent disease.

Blood Forming (Hematopoietic) Stem Cells (HSCs) are the source of stem cell transplantation that is curative in many blood and immune disorders as well as some cancers. One of the major constrains causing the failure of hematopoietic stem cell transplantation is the limited numbers of HSCs available for this procedure in the graft. Ghaffari laboratory has been focused on identifying regulatory pathways that maintain and propagate hematopoietic stem cell numbers.  We have recently uncovered a fundamental mechanism that controls hematopoietic stem cell quiescence and ability to produce all blood lineages. Based on this, we have devised a new approach that remarkably enhances HSC activity. Our current work is partly focused on improving and extending this approach to human HSCs. We are also exploiting this mechanism for abrogating the resistance of leukemia stem cells that are responsible for relapse of leukemia, to therapy.

Erythropoiesis and Red Blood Cells (RBCs) Produced in greatest numbers from hematopoietic stem cells through a process called erythropoiesis, RBCs lack a nucleus and carry oxygen to all tissues, remove carbon dioxide, remodel vessels and are essential for life. Alterations in RBC production leads to anemia and many other blood disorders. Ghaffari laboratory studies mechanisms that regulate RBC production and their alterations in disease. Our recent work suggests that metabolism is directly wired into the generation of RBCs; we are currently pursuing these lines of investigations.

Saghi Ghaffari, MD, PhD
Department of Cell, Developmental, and 
Regenerative Biology
Department of Oncological Sciences
Black Family Stem Cell Institute
Tisch Cancer Institute