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    Paul R Odgren PhD

    TitleResearch Associate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentCell and Developmental Biology
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North
    Worcester MA 01655
    Phone508-856-8509
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCell Biology

        Overview 
        Narrative

        Cell and Developmental Biology Department

        Odgren Lab Website

         

        Biography

        Ph.D. UMass Medical School, 1995
        B.S. UMass Amherst, 1989

        Affiliations

         

        Research Consultant/Visiting Investigator
        The Jackson Laboratory, Bar Harbor, ME,
        2002 – present.

         

         

        Bone and Cartilage Cell Biology

        Deeper knowledge of basic skeletal cell biology has long-range implications for understanding many pervasive clinical conditions, such as osteoporosis, osteoarthritis, and genetic conditions that affect bone growth. Our lab group studies how the cells of the skeleton function and how they communicate and regulate one another, with particular emphasis on the multinucleated, monocyte/macrophage-derived, bone-resorbing osteoclast. Lab website [http://www.umassmed.edu/cellbio/odgrenlab/index.aspx]

        Our main approach has been to use rat and mouse models with genetic abnormalities that block osteoclast differentiation and/or activity, resulting in a condition called osteopetrosis. Osteopetrosis produces dense bones lacking marrow spaces, failure of teeth to erupt through the laws, lack of marrow spaces in the bones, and growth defects due to the failure to remove growth cartilage and to remodel growing bones. Through gene mapping and expression studies, we have identified novel effector genes which play critical roles in osteoclast biology. We have also applied advanced histopatholgical techniques to investigate the detailed impacts of gene function in the tissues, including upon angiogenesis and gene expression. We recently mapped the toothless and incisors absent (ia) mutations in the rat and in so doing discovered a novel gene which also causes osteopetrosis when mutated in humans. Efforts to map the final osteopetrotic mutation in a different rat strain are ongoing in the lab.

        Work in the ia rat model has led to further investigations into the cell biology of the causative gene, called Plekhm1.The plekhm1 protein has a modular, multi-domain structure, suggesting multiple, regulated interactions. Vesicle trafficking and secretion are defective in ia rat osteoclasts, and the co-localization of plekhm1 with the small GTPase, rab7, is the starting point for collaborative investigations we have undertaken with colleagues in Antwerp, Aberdeen, and Frankfurt.

        We have also used gene expression profiling in vivo and in vitro to discover genes which make critical contributions to osteoclast differentiation and activity. This work led to a series of recent papers in which we reported on the entire chemokine and receptor repertoire; the GTP-coupled receptor, OGR1; a novel cell surface receptor we called OC-STAMP; and, in collaboration with investigators at the Forsythe Institute for Dental Medicine in Boston, we have recently described novel mitochondrial and redox proteins.

        Another ongoing collaboration is with investigators at The Jackson Laboratories in Bar Harbor, where we have been helping to investigate and characterize mutant strains of mice with craniofacial defects. A report describing the first naturally-occurring mutation in the lamin A/C gene and its impact on craniofacial and skeletal growth is currently in press.

        Our lab continues the work of Sandy C. Marks, Jr., DDS, PhD, for more on Sandy, follow this link:
        http://www.umassmed.edu/cellbio/sandymarks.aspx

        Download a memorial booklet comprised of contributions from colleagues, and friends worldwide. (PDF 2.3 MB)



        Rotation Projects

        Potential Rotation Projects

        Specific projects will depend on student interests and previous lab experience, but could include digital and/or confocal microscopy, cloning, expression, and analysis of mutant proteins, tissue preparation and staining, Q-PCR, and skeletal phenotyping. Differentiation of osteoclasts from precursors is an ongoing lab focus, and the impact of specific factors on that process is an important area of study.

        Students are encouraged to work on projects of sufficient focus that they are likely to be completed during the rotation period.



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Birnbaum MJ, Picco J, Clements M, Witwicka H, Yang M, Hoey MT, Odgren PR. Using osteoclast differentiation as a model for gene discovery in an undergraduate cell biology laboratory. Biochem Mol Biol Educ. 2010 Nov; 38(6):385-92.
          View in: PubMed
        2. Xu Y, Morse LR, da Silva RA, Odgren PR, Sasaki H, Stashenko P, Battaglino RA. PAMM: a redox regulatory protein that modulates osteoclast differentiation. Antioxid Redox Signal. 2010 Jul 1; 13(1):27-37.
          View in: PubMed
        3. Odgren PR, Pratt CH, Mackay CA, Mason-Savas A, Curtain M, Shopland L, Ichicki T, Sundberg JP, Donahue LR. Disheveled hair and ear (Dhe), a spontaneous mouse Lmna mutation modeling human laminopathies. PLoS One. 2010; 5(4):e9959.
          View in: PubMed
        4. Gartland A, Mason-Savas A, Yang M, MacKay CA, Birnbaum MJ, Odgren PR. Septoclast deficiency accompanies postnatal growth plate chondrodysplasia in the toothless (tl) osteopetrotic, colony-stimulating factor-1 (CSF-1)-deficient rat and is partially responsive to CSF-1 injections. Am J Pathol. 2009 Dec; 175(6):2668-75.
          View in: PubMed
        5. Perdu B, Odgren PR, Van Wesenbeeck L, Jennes K, Mackay CC, Van Hul W. Refined genomic localization of the genetic lesion in the osteopetrosis (op) rat and exclusion of three positional and functional candidate genes, Clcn7, Atp6v0c, and Slc9a3r2. Calcif Tissue Int. 2009 May; 84(5):355-60.
          View in: PubMed
        6. Yang M, Birnbaum MJ, MacKay CA, Mason-Savas A, Thompson B, Odgren PR. Osteoclast stimulatory transmembrane protein (OC-STAMP), a novel protein induced by RANKL that promotes osteoclast differentiation. J Cell Physiol. 2008 May; 215(2):497-505.
          View in: PubMed
        7. Mailhot G, Yang M, Mason-Savas A, Mackay CA, Leav I, Odgren PR. BMP-5 expression increases during chondrocyte differentiation in vivo and in vitro and promotes proliferation and cartilage matrix synthesis in primary chondrocyte cultures. J Cell Physiol. 2008 Jan; 214(1):56-64.
          View in: PubMed
        8. Battaglino RA, Pham L, Morse LR, Vokes M, Sharma A, Odgren PR, Yang M, Sasaki H, Stashenko P. NHA-oc/NHA2: a mitochondrial cation-proton antiporter selectively expressed in osteoclasts. Bone. 2008 Jan; 42(1):180-92.
          View in: PubMed
        9. Li JM, Zhang X, Nelson PR, Odgren PR, Nelson JD, Vasiliu C, Park J, Morris M, Lian J, Cutler BS, Newburger PE. Temporal evolution of gene expression in rat carotid artery following balloon angioplasty. J Cell Biochem. 2007 May 15; 101(2):399-410.
          View in: PubMed
        10. Van Wesenbeeck L, Odgren PR, Coxon FP, Frattini A, Moens P, Perdu B, MacKay CA, Van Hul E, Timmermans JP, Vanhoenacker F, Jacobs R, Peruzzi B, Teti A, Helfrich MH, Rogers MJ, Villa A, Van Hul W. Involvement of PLEKHM1 in osteoclastic vesicular transport and osteopetrosis in incisors absent rats and humans. J Clin Invest. 2007 Apr; 117(4):919-30.
          View in: PubMed
        11. Arnott JA, Nuglozeh E, Rico MC, Arango-Hisijara I, Odgren PR, Safadi FF, Popoff SN. Connective tissue growth factor (CTGF/CCN2) is a downstream mediator for TGF-beta1-induced extracellular matrix production in osteoblasts. J Cell Physiol. 2007 Mar; 210(3):843-52.
          View in: PubMed
        12. Yang M, Mailhot G, Birnbaum MJ, MacKay CA, Mason-Savas A, Odgren PR. Expression of and role for ovarian cancer G-protein-coupled receptor 1 (OGR1) during osteoclastogenesis. J Biol Chem. 2006 Aug 18; 281(33):23598-605.
          View in: PubMed
        13. Odgren PR, MacKay CA, Mason-Savas A, Yang M, Mailhot G, Birnbaum MJ. False-positive beta-galactosidase staining in osteoclasts by endogenous enzyme: studies in neonatal and month-old wild-type mice. Connect Tissue Res. 2006; 47(4):229-34.
          View in: PubMed
        14. Yang M, Mailhot G, MacKay CA, Mason-Savas A, Aubin J, Odgren PR. Chemokine and chemokine receptor expression during colony stimulating factor-1-induced osteoclast differentiation in the toothless osteopetrotic rat: a key role for CCL9 (MIP-1gamma) in osteoclastogenesis in vivo and in vitro. Blood. 2006 Mar 15; 107(6):2262-70.
          View in: PubMed
        15. Gartland A, Mechler J, Mason-Savas A, MacKay CA, Mailhot G, Marks SC, Odgren PR. In vitro chondrocyte differentiation using costochondral chondrocytes as a source of primary rat chondrocyte cultures: an improved isolation and cryopreservation method. Bone. 2005 Oct; 37(4):530-44.
          View in: PubMed
        16. Kim N, Kadono Y, Takami M, Lee J, Lee SH, Okada F, Kim JH, Kobayashi T, Odgren PR, Nakano H, Yeh WC, Lee SK, Lorenzo JA, Choi Y. Osteoclast differentiation independent of the TRANCE-RANK-TRAF6 axis. J Exp Med. 2005 Sep 5; 202(5):589-95.
          View in: PubMed
        17. Wise GE, Yao S, Odgren PR, Pan F. CSF-1 regulation of osteoclastogenesis for tooth eruption. J Dent Res. 2005 Sep; 84(9):837-41.
          View in: PubMed
        18. Yang M, Odgren PR. Molecular cloning and characterization of rat CCL9 (MIP-1gamma), the ortholog of mouse CCL9. Cytokine. 2005 Jul 21; 31(2):94-102.
          View in: PubMed
        19. van Wesenbeeck L, Odgren PR, Mackay CA, Van Hul W. Localization of the gene causing the osteopetrotic phenotype in the incisors absent (ia) rat on chromosome 10q32.1. J Bone Miner Res. 2004 Feb; 19(2):183-9.
          View in: PubMed
        20. Devraj K, Bonassar LJ, MacKay CA, Mason-Savas A, Gartland A, Odgren PR. A new histomorphometric method to assess growth plate chondrodysplasia and its application to the toothless (tl, Csf1(null)) osteopetrotic rat. Connect Tissue Res. 2004; 45(1):1-10.
          View in: PubMed
        21. Ueland T, Odgren PR, Yndestad A, Godang K, Schreiner T, Marks SC, Bollerslev J. Growth hormone substitution increases gene expression of members of the IGF family in cortical bone from women with adult onset growth hormone deficiency--relationship with bone turn-over. Bone. 2003 Oct; 33(4):638-45.
          View in: PubMed
        22. Safadi FF, Xu J, Smock SL, Kanaan RA, Selim AH, Odgren PR, Marks SC, Owen TA, Popoff SN. Expression of connective tissue growth factor in bone: its role in osteoblast proliferation and differentiation in vitro and bone formation in vivo. J Cell Physiol. 2003 Jul; 196(1):51-62.
          View in: PubMed
        23. Odgren PR, Philbrick WM, Gartland A. Perspective. Osteoclastogenesis and growth plate chondrocyte differentiation: emergence of convergence. Crit Rev Eukaryot Gene Expr. 2003; 13(2-4):181-93.
          View in: PubMed
        24. Odgren PR, Kim N, MacKay CA, Mason-Savas A, Choi Y, Marks SC. The role of RANKL (TRANCE/TNFSF11), a tumor necrosis factor family member, in skeletal development: effects of gene knockout and transgenic rescue. Connect Tissue Res. 2003; 44 Suppl 1:264-71.
          View in: PubMed
        25. Bollerslev J, Ueland T, Odgren PR. Serum levels of TGF-beta and fibronectin in autosomal dominant osteopetrosis in relation to underlying mutations and well-described murine counterparts. Crit Rev Eukaryot Gene Expr. 2003; 13(2-4):163-71.
          View in: PubMed
        26. Van Wesenbeeck L, Odgren PR, MacKay CA, D'Angelo M, Safadi FF, Popoff SN, Van Hul W, Marks SC. The osteopetrotic mutation toothless (tl) is a loss-of-function frameshift mutation in the rat Csf1 gene: Evidence of a crucial role for CSF-1 in osteoclastogenesis and endochondral ossification. Proc Natl Acad Sci U S A. 2002 Oct 29; 99(22):14303-8.
          View in: PubMed
        27. Odgren PR, Kim N, van Wesenbeeck L, MacKay C, Mason-Savas A, Safadi FF, Popoff SN, Lengner C, van-Hul W, Choi Y, Marks SC. Evidence that the rat osteopetrotic mutation toothless (tl) is not in the TNFSF11 (TRANCE, RANKL, ODF, OPGL) gene. Int J Dev Biol. 2001 Dec; 45(8):853-9.
          View in: PubMed
        28. Kim N, Odgren PR, Kim DK, Marks SC, Choi Y. Diverse roles of the tumor necrosis factor family member TRANCE in skeletal physiology revealed by TRANCE deficiency and partial rescue by a lymphocyte-expressed TRANCE transgene. Proc Natl Acad Sci U S A. 2000 Sep 26; 97(20):10905-10.
          View in: PubMed
        29. Marks SC, Lundmark C, Christersson C, Wurtz T, Odgren PR, Seifert MF, Mackay CA, Mason-Savas A, Popoff SN. Endochondral bone formation in toothless (osteopetrotic) rats: failures of chondrocyte patterning and type X collagen expression. Int J Dev Biol. 2000 Apr; 44(3):309-16.
          View in: PubMed
        30. Xu J, Smock SL, Safadi FF, Rosenzweig AB, Odgren PR, Marks SC, Owen TA, Popoff SN. Cloning the full-length cDNA for rat connective tissue growth factor: implications for skeletal development. J Cell Biochem. 2000 Feb; 77(1):103-15.
          View in: PubMed
        31. Marks SC, Odgren PR, Popoff SN, Wurtz T. Sutures, growth plates and the craniofacial base--experimental studies in the toothless (tl-osteopetrotic) rat. Ann Acad Med Singapore. 1999 Sep; 28(5):650-4.
          View in: PubMed
        32. Odgren PR, Popoff SN, Safadi FF, MacKay CA, Mason-Savas A, Seifert MF, Marks SC. The toothless osteopetrotic rat has a normal vitamin D-binding protein-macrophage activating factor (DBP-MAF) cascade and chondrodysplasia resistant to treatments with colony stimulating factor-1 (CSF-1) and/or DBP-MAF. Bone. 1999 Aug; 25(2):175-81.
          View in: PubMed
        33. Marks SC, Lundmark C, Wurtz T, Odgren PR, MacKay CA, Mason-Savas A, Popoff SN. Facial development and type III collagen RNA expression: concurrent repression in the osteopetrotic (Toothless,tl) rat and rescue after treatment with colony-stimulating factor-1. Dev Dyn. 1999 Jun; 215(2):117-25.
          View in: PubMed
        34. Feister HA, Swartz D, Odgren PR, Holden J, Hock JM, Onyia J, Bidwell JP. Topoisomerase II expression in osseous tissue. J Cell Biochem. 1997 Dec 15; 67(4):451-65.
          View in: PubMed
        35. Odgren PR, Hermey DC, Popoff SN, Marks SC. Cellular and molecular strategies for studying the regulation of bone resorption using the toothless (osteopetrotic) mutation in the rat. Histol Histopathol. 1997 Oct; 12(4):1151-7.
          View in: PubMed
        36. van Wijnen AJ, Cooper C, Odgren P, Aziz F, De Luca A, Shakoori RA, Giordano A, Quesenberry PJ, Lian JB, Stein GS, Stein JL. Cell cycle-dependent modifications in activities of pRb-related tumor suppressors and proliferation-specific CDP/cut homeodomain factors in murine hematopoietic progenitor cells. J Cell Biochem. 1997 Sep 15; 66(4):512-23.
          View in: PubMed
        37. Odgren PR, Toukatly G, Bangs PL, Gilmore R, Fey EG. Molecular characterization of mitofilin (HMP), a mitochondria-associated protein with predicted coiled coil and intermembrane space targeting domains. J Cell Sci. 1996 Sep; 109 ( Pt 9):2253-64.
          View in: PubMed
        38. Thiede MA, Smock SL, Mason-Savas A, MacKay CA, Odgren PR, Marks SC. Thrombocytopenia in the toothless (osteopetrotic) rat and its rescue by treatment with colony-stimulating factor-1. Exp Hematol. 1996 May; 24(6):722-7.
          View in: PubMed
        39. Bangs PL, Sparks CA, Odgren PR, Fey EG. Product of the oncogene-activating gene Tpr is a phosphorylated protein of the nuclear pore complex. J Cell Biochem. 1996 Apr; 61(1):48-60.
          View in: PubMed
        40. Odgren PR, Harvie LW, Fey EG. Phylogenetic occurrence of coiled coil proteins: implications for tissue structure in metazoa via a coiled coil tissue matrix. Proteins. 1996 Apr; 24(4):467-84.
          View in: PubMed
        41. Birnbaum MJ, van Wijnen AJ, Odgren PR, Last TJ, Suske G, Stein GS, Stein JL. Sp1 trans-activation of cell cycle regulated promoters is selectively repressed by Sp3. Biochemistry. 1995 Dec 19; 34(50):16503-8.
          View in: PubMed
        42. Guo B, Odgren PR, van Wijnen AJ, Last TJ, Nickerson J, Penman S, Lian JB, Stein JL, Stein GS. The nuclear matrix protein NMP-1 is the transcription factor YY1. Proc Natl Acad Sci U S A. 1995 Nov 7; 92(23):10526-30.
          View in: PubMed
        43. Fey EG, Bangs P, Sparks C, Odgren P. The nuclear matrix: defining structural and functional roles. Crit Rev Eukaryot Gene Expr. 1991; 1(2):127-43.
          View in: PubMed
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