Left to Right: Phyo Htun, Megan Walker, Miguel Ganuza, Shannon McKinney-Freeman, Maheen Ferdous, Trent Hall and Himangi Marathe
The McKinney-Freeman lab is focused on better understanding the fundamental biology of hematopoietic stem cells (HSC), especially the genetic and cellular regulation of their in vivo repopulating activity. HSC are currently the most therapeutically exploited adult stem cell compartment, used routinely to treat leukemia and hematologic disease via HSC transplantation. However, many patients that might benefit from HSC transplantation lack access to a suitable donor.
By better understanding the intrinsic and extrinsic factors that control the ability of HSC to home to, engraft, and repopulate the hematopoietic compartment after transplantation, we hope to design therapies targeted at improving the efficiency with which HSC engraft patients. This would allow us to expand access to this life-saving therapy by making it possible for more patients to take advantage of valuable sources of HSC for transplantation, such as cord blood, whose application is limited by small cell numbers. We recently completed a functional screen in which we identified 20 genes as novel regulators of HSC in vivo hematopoietic repopulating activity. We are currently working to dissect the cellular and molecular mechanisms by which these genes regulate the function of HSC.
We are also interested in discovering novel genes that regulate the specification and development of HSC during embryogenesis. This work is crucial to the larger goal of engineering HSC from pluripotent stem cells (PSC) as an alternative resource to patients in need of HSC transplantation. In order to direct the fate of PSC 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 numerous genes as potential regulators of HSC development. We are currently investigating prioritized genes for a role in this process.
The Hartwell Foundation
The American Society for Hematology
St. Jude Children's Research Hospital Comprehensive Cancer Center