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McKinney-Freeman Lab: About Us

Welcome to the lab of Shannon McKinney-Freeman, PhD

McKinney-Freeman Lab Team

Front Row (L to R): Ashley Chabot, Shannon McKinney-Freeman, Megan Walker; Back Row (L to R): Trent Hall, Charly La Maout, Shobhit Saxena, Mikel Ganuza, and Antonio Morales-Hernandez

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 working to better understand the specification and development of HSC and the hematopoietic hierarchy during embryogenesis. This knowledge is crucial for better understanding the putative developmental origins of hematologic disease (especially in young children). We are currently investigating the evolution of the clonal diversity of the hematopoietic system during development and throughout life, as well as exploring how the hematopoietic hierarchy of stem and progenitor cells is established in the developing bone marrow. Further, pluripotent stem cells (PSC) are one promising alternative source of HSC for patients in need of HSC transplantation. 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 implicated numerous genes as potential regulators of HSC development. We are currently investigating prioritized genes for a role in this process to further illuminate the molecular regulation of HSC specification during embryogenesis. 

Funding:

  • ALSAC

  • The American Society for Hematology

  • Leukemia and Lymphoma Society

  • NIH NIDDK