Research
Interests
Presently, the Wojchowski laboratory pursues three research interest areas: 1) growth factor and receptor action with a focus on erythropoietin (EPO), EPO receptor (EPOR) and erythropoiesis; 2) EPO/EPOR actions in non-hematopoietic contexts, including cytoprotection and cancer progression; and 3) new interests in stem cell biology.
In response to hypoxia, EPO is produced by renal interstitial fibroblasts, and targets CFUe-like erythroid progenitors within bone marrow. EPO specifically induces the expansion of this progenitor pool, and as an injectable recombinant sialylglycoprotein, is clinically important for the treatment of anemia. EPO also has been demonstrated to cytoprotect ischemically injured cells within heart, kidney, and brain. In a compromising context, EPO in addition appears to promote the progression of several cancers.
The above considerations intensify interests in advancing a more sophisticated understanding of EPO/EPOR action. Towards this, our laboratory recently has employed primary bone marrow erythroid progenitor cells expressing knocked-in minimal EPOR alleles together with global transcriptome approaches to discover new EPO/EPOR response circuits. As described in five recent papers (see publication list) these investigations have provided novel insight into EPO/EPOR action. This includes novel EPO effects on cell surface adhesion/migration factors, cell cycle regulators and new cell survival factors. In addition, we have provided strong evidence that an EPOR/JAK2/STAT5 signaling axis acts specifically to support erythropoiesis during anemia.
To critically and functionally advance knowledge of our newly discovered EPO response factors, we now have successfully established several novel knock-out and transgenic mouse models which are proving to exhibit intriguing phenotypes. We also are now quite actively applying our expertise in EPO/EPOR action to investigate mechanisms underlying EPO’s cytoprotective effects on renal tubular epithelial cells, and cancer progression.
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Selected
Publications
Sathyanarayana P, Dev A, Fang J, Houde E, Bogacheva O, Bogachev O, Menon M, Browne S, Pradeep A, Emerson C, Wojchowski DM. EPO receptor circuits for primary erythroblast survival. Blood, 2008; 111:5390-9 (PMCID: PMC2396729)
Fang J, Menon M, Zhang D, Torbett B, Oxburgh L, Tschan M, Houde E, and Wojchowski DM. Attenuation of EPO-dependent erythroblast formation by death associated protein kinase-2. Blood, 2008; June 5 Epub. (PMCID: PMC2481541)
Sathyanarayana P, Menon M, Bogacheva O, Bogachev O, Niss K, Kapelle W, Houde E, Fang J, Wojchowski DM. Erythropoietin modulation of podocalyxin and a proposed erythroblast niche. Blood, 2007; 110:509-18. (PMCID: PMC1924484)
Fang J, Menon M, Kapelle W, Bogacheva O, Bogachev O, Houde E, Browne S, Sathyanarayana P, Wojchowski DM. EPO modulation of cell-cycle regulatory genes, and cell division, in primary bone marrow erythroblasts. Blood, 2007; 110:2361-70. (PMCID: PMC1988929)
Menon M, Karur V, Bogacheva O, Bogachev O, Cuetara B, Wojchowski DM. Signals for stress erythropoiesis are integrated via an erythropoietin receptor phosphotyrosine-343-Stat5 axis J Clin Invest, 2006; 116:683-94. (PMCID: PMC1386105)
Available Positions:
Scientist/Postdoctoral Position(s) - H601BL
Opportunities exist to assume a lead role in Institute-, NIH- and corporate- sponsored investigations of: 1/ erythroid progenitor cell development (including novel niche-specific Epo action modes, and response factors); 2/ newly discovered tyrosine and S/T kinases with hematopoietic suppressor activities; and 3/ the nature (and action mechanisms) of unique cell migration and adhesion factors involved in cytokine-dependent erythroid, megakaryocytic and myeloid progenitor cell development.
Approaches include new transgenic and knockout mouse models; systems for primary cell development ex vivo; transcriptome analyses and bioinformatics; and human CD34 cell & lentiviral RNAi systems. Opportunities also exist for participation in: studies of small molecule inhibitors & cytokine mimetics; & human patient samples/studies; and graduate & undergraduate teaching. Resources include subsidized cores in: Progenitor Cell Separation and Analysis; Genomics & Bioinformatics;Transgenic mouse construction; Lenti- and retro-virus production; Confocal microscopy; DNA & protein sequencing; Histopathology; and Small animal MRI.
Benefits, salary and resources are nationally competitive and positions are within the laboratory of DM Wojchowski at the Maine Medical Center Research Institute, (www.mmcri.org.) Please send CV, statement of research interests, and professional reference contact information to: resumes@mmc.org
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