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CURRENT RESEARCH
INTEREST
Hematopoiesis
RESEARCH DESCRIPTION
Regulation of Megakaryocytopoiesis/Thrombocytopoiesis. Hematopoietic stem cells capable of self-renewal proliferate and differentiate to produce mature megakaryocytes (MKs) that eventually shed their platelets. This multi-stage biological process results in a constant number of mature circulating platelets that sustain an individual throughout their lifespan. Under steady-state conditions, approximately 40,000 platelets/ml or 200 billion platelets per day are produced in healthy individuals. Clinical consequences of alterations in platelet numbers and function range from severe thromboembolic episodes due to high platelet counts to life-threatening bleeding episodes due to functionally inactive or low numbers of circulating platelets. Thus, a readily available supply of allogeneic platelets for transfusion purposes continues to be an extremely beneficial resource for treating patients with a variety of disorders (i.e. cancer, surgery, trauma).
The focus of our laboratory is to identify regulatory mechanisms responsible for the proliferation and differentiation of hematopoietic progenitor cells along the MK/platelet lineage. Ultimately, for the purpose of developing an in vitro approach to amplify hematopoietic stem cells and to then selectively direct them to produce platelets for transfusion purposes. To accomplish this goal, we are using methodologies from the disciplines of cellular and molecular biology to identify and modulate extrinsic and intrinsic factors that control the growth and development of MKs/platelets. More specifically, we used transcript profiling to publish the first comprehensive global expression profile of MKs (Shim M-H, et al., 2004). This new library of information is now being explored to identify new genes not previously associated with MK development. As a result of these studies, we are now using a variety of strategies (e.g. gene transduction, chemical inhibitors) to modulate the function of a number of selected genes to determine their effect on the growth and development of MKs/platelets during in vitro culture.
SELECTED PUBLICATIONS
Reems JA and McHenry CS: E. coli DNA polymerase III holoenzyme protects 3 helical repeats of primer-template.
J. Biol. Chem. 269:33091-33096, 1994.
Reems JA, Wood S, and McHenry CS: E. coli DNA Polymerase III holoenzyme subunits, a, b, and g directly interact with primer-template.
J. Biol. Chem. 270:5606-5613, 1995.
Reems JA, and Torok-Storb B: Cell-cycle and functional analysis of in vitro stimulated human CD34+/CD38lo and CD34+/CD38hi hematopoietic progenitor cells.
Blood 85:1480-1487, 1995.
Reems JA, Mielcarek M, Torok-Storb B: Differential modulation of adhesion markers with ex vivo expansion of human umbilical CD34+ cells.
Biol. Blood Marrow Transpl. 3:133-141, 1997.
Xu R, Reems JA: Umbilical cord blood progeny cells expressing the CD34+ phenotype post-expansion have reduced engraftment potential relative to unexpanded CD34+ cells.
Transfusion (In press).
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