Don M. Wojchowski, Professor of Biomedical Sciences, MCBS Department and COLSA, UNH Durham:
Dr Wojchowski was recruited to UNH in Fall 2017 from Maine Medical Center (MMC) and Tufts University Dept of Medicine. At MMC, he was Director/PI of an NIH Center of Biomedical Research Excellence (COBRE) in Regenerative Medicine (2005 – 2017), and of research programs in hematology, erythropoiesis and anemia. This followed his professorship at Penn State University which included NIH and biopharma hematology research, Directorship of PSU’s Graduate Immunobiology Program, and teaching in molecular and cellular biology disciplines. At UNH, Dr Wojchowski’s administrative efforts include UNH representative to Biotech, Biopharma; NIH COBRE Bioengineering Center Leadership Team member; service as chair and member on major MCBS, COLSA, UNH committees; MCB Core Facilities Director; MCBS and COBRE faculty mentor; and PI of his NIH hematology research program.
In the Wojchowski laboratory, research focuses on cellular and molecular action mechanisms of hematopoietic growth factors (HGFs), including erythropoietin (EPO). The EPO/EPOR/JAK2 receptor system is an incisive model that continues to advance the field’s understanding of receptor activation mechanisms and cell type- specific signaling pathways. During anemia, EPO expression is induced in hypoxia- sensing renal tubular fibroblastic cells. In bone marrow, EPO binds to cell surface homo-dimeric EPO receptors (EPOR’s) on erythroid progenitor cells (EPCs), and activates co-assembled JAK2 kinases. Select EPO/EPOR/JAK2 stimulated pY- phosphorylation events then trigger EPOR signalosome assembly, and signal transduction events essential for EPC growth and development. Understanding these events is scientifically and clinically significant in that EPO, the EPOR and JAK2 each are required for erythropoiesis and red blood cell production; rhEPO is an important anti-anemia agent for chronic renal disease, myelodysplastic syndrome, and chemotherapy patients; and dysregulated JAK kinases are important drug targets in myeloproliferative disease, certain leukemias and rheumatoid arthritis.
Our group was among the first to clone EPO, to reconstitute EPOR function, to identify key roles for an EPOR/JAK2/STAT5 signaling axis during stress erythropoiesis, and to employ gene profiling to identify important new mediators of EPO’s cell growth and survival effects. In ongoing studies, by employing PTM-proteomic approaches, we have uncovered several fully novel EPO target proteins that are proving to be important new regulators of EPO/EPOR signaling and JAK2. These include “C1ORF150”, a novel orthologue of HGAL, that protects against erythroid progenitor hyper-proliferation, and “C1ORF186”/RHEX that is required for effective EPO-dependent late stage human erythroblast development. Each is proving to function as a plasma membrane localized adaptor protein. Each additionally is conserved in H sapiens and primates but is not represented in mice, rats or lower vertebrates. A second area of research in our laboratory focuses on new biotechnological inroads to define protein and protein PTM signatures that predict (and quantitatively validate) progenitor cell potentials and their lineage-specific development.
Teaching efforts include the development and instruction of courses in Cell and Tissue Engineering; Cell and Molecular Signal Transduction; and Infectious Disease and Health. A new course in Disease Mechanisms and Therapeutics is also under development.
