Left to Right: Miguel Ganuza, Per Holmfeldt, Harrison Daniel, Alba Cico, Shannon McKinney-Freeman. Anjelica Saulsberry, Jennifer Pardieck, Phyo Htun, and Daniel Elridge
The McKinney-Freeman lab would like to take advantage of pluripotent stem cells (PSCs) to generate cells that could be used to treat disease. We are particularly interested in discovering ways to direct PSCs to make hematopoietic stem cells (HSCs), the adult stem cell that resides in bone marrow and is responsible for the maintenance and production of the hematopoietic system. HSCs are currently the most therapeutically exploited adult stem cell compartment, used routinely to treat leukemia and bone marrow failure disorders via bone marrow transplantation. Many patients who might benefit from HSC transplantation, however, lack access to a suitable donor. We believe that PSC-derived HSCs could serve as a life-saving resource to many patients in need of bone marrow transplantation.
Our lab is currently focused on discovering novel genes involved in the specification and development of HSCs. This work is crucial to our goal of isolating HSCs from PSCs because, in order to direct their fate towards a specific cell lineage, one must have an in-depth understanding of the molecular mechanisms that regulate the specification of that cell type during normal embryonic development. We recently completed a computational screen that has implicated about 160 genes as potential regulators of HSC development. We are currently assessing prioritized candidate genes for a role in HSC function and specification by manipulating candidate gene expression in both highly purified adult HSC and the newly specified HSC of the mid-gestation embryo. Once we have identified genes that can perturb the specification of the HSC during normal development, we will assess the impact of these genes and the pathways they regulate, on the ability of PSCs to differentiate into HSCs.