Research interests

My laboratory's broad interests include molecular mechanisms that govern mammalian progenitor cell proliferation, survival and differentiation. Hematopoiesis (blood cell development) serves as a prime model system, and provides an exceptional example of sustained tissue regeneration from a multipotent progenitor pool. This developmental process also is frequently perturbed clinically (leukemias, blood cell disorders, cancer) and provides unique advantages for bench investigations (e.g., via transplantation, repopulation and in vitro expansion).

Erythropoiesis is one focus of our investigations. Red blood cells form continuously at remarkable rates, and defects in their formation are common (e.g., anemias associated with chemotherapy and renal or chronic disease). Key factors that regulate erythropoiesis are incompletely understood, and our investigations may reveal new molecular targets for anti-anemia agents. Related problems under study include: 1) Epo receptor action mechanisms; 2) co-signaling factors that promote progenitor cell development (including RTKs, PTKs and lineage-restricted transcription factors); and 3) actions of a novel erythroid-restricted dual specificity kinase, DYRK3.

Emerging new interests for our research team include Epo receptor function in non-hematopoietic tissues and cytokine receptor systems that regulate the renewal (vs. developmental commitment) of early progenitor cells.

Publications

• D Zhang, K Li, DM Wojchowski. Stage-specific gene expression programs during late erythropoiesis (in preparation, 2004)
• V Karur, M Menon, DM Wojchowski. Critical roles for an Epo receptor/PY343/Stat5 signaling axis during stress erythropoiesis (in preparation, 2004)
• K Li, M Menon, V Karur, S Hegde, DM Wojchowski. Attenuated signaling by a phosphotyrosine-null Epo receptor form in primary erythroid progenitor cells. Blood 102:3147-3153, 2003
• K Li, S Hedge, DM Wojchowski. Roles for an Epo Receptor Tyr-343 Stat5 pathway in proliferative co-signaling with Kit. Journal of Biological Chemistry 278:40702-40709, 2003
• CP Miller, DW Heilman, DM Wojchowski. Erythropoietin receptor-dependent erythroid colony-forming unit development: capacities of Y343 and phosphotyrosine-null receptor forms. Blood 99:898-904, 2002
• K Li, S Zhao, V Karur, DM Wojchowski. DYRK3 activation, engagement of protein kinase A/cAMP response element-binding protein, and modulation of progenitor cell survival. Journal of Biological Chemistry 277:47052-60, 2002
• JN Geiger, GT Knudsen, A Pandit, L Panek, M Yoder, K Lord, CL Creasy, BM Burns, S Dillon, DM Wojchowski. mDYRK3 kinase is expressed selectively in late erythroid progenitor cells and attenuates CFUe development. Blood 97:901-910, 2001
• TJ Pircher, JN Geiger, D Zhang, CP Miller, P. Gaines, DM Wojchowski. Integrative signaling by minimal erythropoietin receptor forms and c-Kit. Journal of Biological Chemistry 276:8995-9002, 2001
• P Gaines, JN Geiger, G Knudsen, D Seshasayee, DM Wojchowski. GATA-l- and FOG-dependent activation of megakaryocytic alpha lIB gene expression. Journal of Biological Chemistry 275:34114-21, 2000
• D Seshasayee, P Gaines, DM Wojchowski. GATA-l dominantly activates a program of erythroid gene expression in factor-dependent myeloid FDCW2 cells. Molecular and Cellular Biology, 18: 3278-3288, 1998
• H Zhang, SV Patel, TC He, SK Sonsteby, Z Niu, DM Wojchowski. Inhibition of erythropoietin-induced mitogenesis by a kinase-deficient form of Jak2. Journal of Biological Chemistry 269:21411-4, 1994
• DE Quelle and DM Wojchowski. Localized cytosolic domains of the erythropoietin receptor regulate growth signaling and down-modulate responsiveness to granulocyte-macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 88:4801-5, 1991