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    Mary Nakamura, MD

    TitleAssociate Professor
    SchoolUCSF School of Medicine
    DepartmentMedicine
    AddressVAMC 2, Room 531
    Phone415-750-2104x3458

       Biography 
       Education and Training
      Institution Degree School or Department Year
      University of California, San FranciscoResidency Internal Medicine
       Awards and Honors
      American College of Rheumatology 2005Henry Kunkel Young Investigator Award
      UCSF2004Ira M. Goldstein Award for Outstanding Teaching in Rheumatology
      President of US 2000Presidential Early Career Award
      VA1998VA Career Development Award
      ACR1993Physician Scientist Development Award
      UCSF1989Jeffrey Weingarten Award for Housestaff
      Yale Medical School 1986J.M. Glasgow Memorial AMWA scholastic citation
      Yale Medical School 1986Louis G. Welt Prize for medical school thesis

       Overview 
       Overview
      My research has focused on the study of the receptors that regulate cells in the innate immune system. We previously examined receptors on natural killer cell lymphocytes, but currently focus our work on similar receptors on osteoclasts. Our research is a major area of interest in the recently defined field of study termed osteoimmunology. Osteoimmunology is defined as a cross disciplinary field to integrate studies of the immune system and studies of bone and better define the interactions between these systems.
      Osteoclasts are the only bone resorbing cell, and are derived from monocyte/macrophage precursors. Osteoclast differentiation was previously demonstrated to require the stimulation by specific cytokines (RANKL and MCSF), but the roles of other immune receptors has only recently been investigated. Our studies demonstrated that innate immune receptors that utilize ITAM or immunoreceptor tyrosine based activation motif signals are also critical regulators of osteoclast development and function, during normal bone development and homeostasis. We demonstrated that mice deficient in the ITAM adapter signaling chains DAP12 and FcR? are severly osteopetrotic due to defective osteoclast differentiation and function. Our studies suggest that osteoclasts are regulated much like other innate immune cells such as natural killer cells, macrophages and dendritic cells and should be considered an integral part of the innate immune system. I have chosen to focus the recent work in my laboratory on osteoimmunology since the role of innate immune receptor regulation in the bone in an understudied area, and inflammatory bone loss is of direct importance in rheumatologic diseases. My overall goal is to examine the role of innate immune receptors in autoimmune disease states and bone remodeling, which best integrates my research interests with my clinical subspecialty work. Until recently we have examined only murine osteoclasts and mouse models of disease, but we have initiated work on murine ostoblasts and human osteoclasts in addition and have begun translational studies on osteoclast precursors in rheumatoid arthritis patients.


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       Bibliographic 
       Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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      1. Hsieh CL, Niemi EC, Wang SH, Lee CC, Bingham D, Zhang J, Cozen M, Charo IF, Huang EJ, Liu J, Nakamura MC. CCR2 deficiency impairs macrophage infiltration and improves cognitive function after traumatic brain injury. J Neurotrauma. 2014 May 7.
        View in: PubMed
      2. Charles JF, Nakamura MC. Bone and the innate immune system. Curr Osteoporos Rep. 2014 Mar; 12(1):1-8.
        View in: PubMed
      3. Nakamura MC. CIITA: A Master Regulator of Adaptive Immunity Shows Its Innate Side in the Bone. J Bone Miner Res. 2014 Feb; 29(2):287-9.
        View in: PubMed
      4. Hsieh CL, Kim CC, Ryba BE, Niemi EC, Bando JK, Locksley RM, Liu J, Nakamura MC, Seaman WE. Traumatic brain injury induces macrophage subsets in the brain. Eur J Immunol. 2013 Aug; 43(8):2010-22.
        View in: PubMed
      5. Charles JF, Hsu LY, Niemi EC, Weiss A, Aliprantis AO, Nakamura MC. Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function. J Clin Invest. 2012 Dec 3; 122(12):4592-605.
        View in: PubMed
      6. Chitu V, Nacu V, Charles JF, Henne WM, McMahon HT, Nandi S, Ketchum H, Harris R, Nakamura MC, Stanley ER. PSTPIP2 deficiency in mice causes osteopenia and increased differentiation of multipotent myeloid precursors into osteoclasts. Blood. 2012 Oct 11; 120(15):3126-35.
        View in: PubMed
      7. Hammer GE, Turer EE, Taylor KE, Fang CJ, Advincula R, Oshima S, Barrera J, Huang EJ, Hou B, Malynn BA, Reizis B, DeFranco A, Criswell LA, Nakamura MC, Ma A. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol. 2011 Dec; 12(12):1184-93.
        View in: PubMed
      8. Baker-LePain JC, Nakamura MC, Lane NE. Effects of inflammation on bone: an update. Curr Opin Rheumatol. 2011 Jul; 23(4):389-95.
        View in: PubMed
      9. Baker-LePain JC, Nakamura MC, Shepherd J, von Scheven E. Assessment of bone remodelling in childhood-onset systemic lupus erythematosus. Rheumatology (Oxford). 2011 Mar; 50(3):611-9.
        View in: PubMed
      10. Adapala NS, Barbe MF, Langdon WY, Nakamura MC, Tsygankov AY, Sanjay A. The loss of Cbl-phosphatidylinositol 3-kinase interaction perturbs RANKL-mediated signaling, inhibiting bone resorption and promoting osteoclast survival. J Biol Chem. 2010 Nov 19; 285(47):36745-58.
        View in: PubMed
      11. Baker-LePain JC, Stone DH, Mattis AN, Nakamura MC, Fye KH. Clinical diagnosis of segmental arterial mediolysis: differentiation from vasculitis and other mimics. Arthritis Care Res (Hoboken). 2010 Nov; 62(11):1655-60.
        View in: PubMed
      12. Xing Z, Lu C, Hu D, Yu YY, Wang X, Colnot C, Nakamura M, Wu Y, Miclau T, Marcucio RS. Multiple roles for CCR2 during fracture healing. Dis Model Mech. 2010 Jul-Aug; 3(7-8):451-8.
        View in: PubMed
      13. Li L, Fang CJ, Ryan JC, Niemi EC, Lebrón JA, Björkman PJ, Arase H, Torti FM, Torti SV, Nakamura MC, Seaman WE. Binding and uptake of H-ferritin are mediated by human transferrin receptor-1. Proc Natl Acad Sci U S A. 2010 Feb 23; 107(8):3505-10.
        View in: PubMed
      14. Park-Min KH, Ji JD, Antoniv T, Reid AC, Silver RB, Humphrey MB, Nakamura M, Ivashkiv LB. IL-10 suppresses calcium-mediated costimulation of receptor activator NF-kappa B signaling during human osteoclast differentiation by inhibiting TREM-2 expression. J Immunol. 2009 Aug 15; 183(4):2444-55.
        View in: PubMed
      15. Hsieh CL, Koike M, Spusta SC, Niemi EC, Yenari M, Nakamura MC, Seaman WE. A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J Neurochem. 2009 May; 109(4):1144-56.
        View in: PubMed
      16. Yao W, Cheng Z, Busse C, Pham A, Nakamura MC, Lane NE. Glucocorticoid excess in mice results in early activation of osteoclastogenesis and adipogenesis and prolonged suppression of osteogenesis: a longitudinal study of gene expression in bone tissue from glucocorticoid-treated mice. Arthritis Rheum. 2008 Jun; 58(6):1674-86.
        View in: PubMed
      17. Charles JF, Humphrey MB, Zhao X, Quarles E, Nakamura MC, Aderem A, Seaman WE, Smith KD. The innate immune response to Salmonella enterica serovar Typhimurium by macrophages is dependent on TREM2-DAP12. Infect Immun. 2008 Jun; 76(6):2439-47.
        View in: PubMed
      18. Wu Y, Humphrey MB, Nakamura MC. Osteoclasts - the innate immune cells of the bone. Autoimmunity. 2008 Apr; 41(3):183-94.
        View in: PubMed
      19. Wu Y, Torchia J, Yao W, Lane NE, Lanier LL, Nakamura MC, Humphrey MB. Bone microenvironment specific roles of ITAM adapter signaling during bone remodeling induced by acute estrogen-deficiency. PLoS One. 2007; 2(7):e586.
        View in: PubMed
      20. Hamerman JA, Jarjoura JR, Humphrey MB, Nakamura MC, Seaman WE, Lanier LL. Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. J Immunol. 2006 Aug 15; 177(4):2051-5.
        View in: PubMed
      21. Humphrey MB, Lanier LL, Nakamura MC. Role of ITAM-containing adapter proteins and their receptors in the immune system and bone. Immunol Rev. 2005 Dec; 208:50-65.
        View in: PubMed
      22. Humphrey MB, Daws MR, Spusta SC, Niemi EC, Torchia JA, Lanier LL, Seaman WE, Nakamura MC. TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. J Bone Miner Res. 2006 Feb; 21(2):237-45.
        View in: PubMed
      23. Chen TT, Li L, Chung DH, Allen CD, Torti SV, Torti FM, Cyster JG, Chen CY, Brodsky FM, Niemi EC, Nakamura MC, Seaman WE, Daws MR. TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis. J Exp Med. 2005 Oct 3; 202(7):955-65.
        View in: PubMed
      24. Lane NE, Yao W, Nakamura MC, Humphrey MB, Kimmel D, Huang X, Sheppard D, Ross FP, Teitelbaum SL. Mice lacking the integrin beta5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state. J Bone Miner Res. 2005 Jan; 20(1):58-66.
        View in: PubMed
      25. Mócsai A, Humphrey MB, Van Ziffle JA, Hu Y, Burghardt A, Spusta SC, Majumdar S, Lanier LL, Lowell CA, Nakamura MC. The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proc Natl Acad Sci U S A. 2004 Apr 20; 101(16):6158-63.
        View in: PubMed
      26. Humphrey MB, Ogasawara K, Yao W, Spusta SC, Daws MR, Lane NE, Lanier LL, Nakamura MC. The signaling adapter protein DAP12 regulates multinucleation during osteoclast development. J Bone Miner Res. 2004 Feb; 19(2):224-34.
        View in: PubMed
      27. Chung DH, Humphrey MB, Nakamura MC, Ginzinger DG, Seaman WE, Daws MR. CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation. J Immunol. 2003 Dec 15; 171(12):6541-8.
        View in: PubMed
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