Mary Nakamura, MD

InstitutionUniversity of California San Francisco
AddressVAMC 2, Room 531
San Francisco CA 94121
Phone415-750-2104 ext. 3458
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    Collapse Biography 
    Collapse Education and Training
    Swarthmore College BA 1981Biology
    Yale UniversityMD1986School of Medicine
    University of California, San FranciscoResidency 1989Internal Medicine
    Johns Hopkins University Fellowship1991Rheumatology
    University of California, San FranciscoFellowship 1994Rheumatology
    Collapse 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

    Collapse Overview 
    Collapse 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.

    Collapse Research 
    Collapse Research Activities and Funding
    Immune Modulation and Cardiac Remodeling
    VA I01BX002994Oct 1, 2016 - Sep 30, 2020
    Role: Principal Investigator
    Effects of Aging on Macrophages and Bone Regeneration
    NIH/NIA R01AG046282Sep 30, 2013 - Jun 30, 2017
    Role: Co-Principal Investigator
    DAP12 and ITAM-signals in Osteoclastogenesis
    VA I01BX000615Oct 1, 2009 - Mar 31, 2014
    Role: Principal Investigator
    Using VEGF expression in inflammatory arthritis to induce targeted apoptosis
    NIH/NIAMS R21AR056365Aug 1, 2008 - Apr 30, 2011
    Role: Principal Investigator
    NIH/NIAMS R01AR050038Aug 1, 2004 - Jun 30, 2010
    Role: Principal Investigator
    NIH/NIAMS K11AR001927May 1, 1994 - Jun 30, 2000
    Role: Principal Investigator

    Collapse ORNG Applications 
    Collapse Websites
    Collapse Faculty Mentoring
    Collapse Featured Videos

    Collapse Bibliographic 
    Collapse 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.
    List All   |   Timeline
    1. Clark D, Nakamura M, Miclau T, Marcucio R. Effects of Aging on Fracture Healing. Curr Osteoporos Rep. 2017 Dec; 15(6):601-608. PMID: 29143915.
      View in: PubMed
    2. Humphrey MB, Nakamura M. A Comprehensive Review of Immunoreceptor Regulation of Osteoclasts. Clin Rev Allergy Immunol. 2016 Aug; 51(1):48-58. PMID: 26573914; PMCID: PMC4867136 [Available on 08/01/17].
    3. Kim CC, Nakamura M, Hsieh CL. Brain trauma elicits non-canonical macrophage activation states. J Neuroinflammation. 2016 05 24; 13(1):117. PMID: 27220367.
      View in: PubMed
    4. Kawabori M, Kacimi R, Kauppinen T, Calosing C, Kim JY, Hsieh CL, Nakamura M, Yenari MA. Triggering receptor expressed on myeloid cells 2 (TREM2) deficiency attenuates phagocytic activities of microglia and exacerbates ischemic damage in experimental stroke. J Neurosci. 2015 Feb 25; 35(8):3384-96. PMID: 25716838; PMCID: PMC4339351.
    5. Hsieh CL, Niemi EC, Wang SH, Lee CC, Bingham D, Zhang J, Cozen ML, Charo I, Huang EJ, Liu J, Nakamura M. CCR2 deficiency impairs macrophage infiltration and improves cognitive function after traumatic brain injury. J Neurotrauma. 2014 Oct 15; 31(20):1677-88. PMID: 24806994; PMCID: PMC4545982.
    6. Charles JF, Nakamura M. Bone and the innate immune system. Curr Osteoporos Rep. 2014 Mar; 12(1):1-8. PMID: 24500569; PMCID: PMC3992341.
    7. Nakamura M. CIITA: a master regulator of adaptive immunity shows its innate side in the bone. J Bone Miner Res. 2014 Feb; 29(2):287-9. PMID: 24343972; PMCID: PMC4852740.
    8. Kawabori M, Hokari M, Zheng Z, Kim JY, Calosing C, Hsieh CL, Nakamura M, Yenari MA. Triggering Receptor Expressed on Myeloid Cells-2 Correlates to Hypothermic Neuroprotection in Ischemic Stroke. Ther Hypothermia Temp Manag. 2013 Dec 01; 3(4):189-198. PMID: 24380032.
      View in: PubMed
    9. Hsieh CL, Kim CC, Ryba BE, Niemi EC, Bando JK, Locksley RM, Liu J, Nakamura M, Seaman WE. Traumatic brain injury induces macrophage subsets in the brain. Eur J Immunol. 2013 Aug; 43(8):2010-22. PMID: 23630120; PMCID: PMC4210355.
    10. Charles JF, Hsu LY, Niemi EC, Weiss A, Aliprantis AO, Nakamura M. Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function. J Clin Invest. 2012 Dec; 122(12):4592-605. PMID: 23114597; PMCID: PMC3533532.
    11. Chitu V, Nacu V, Charles JF, Henne WM, McMahon HT, Nandi S, Ketchum H, Harris R, Nakamura M, 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. PMID: 22923495; PMCID: PMC3471520.
    12. 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 M, Ma A. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol. 2011 Oct 23; 12(12):1184-93. PMID: 22019834.
      View in: PubMed
    13. Baker-LePain JC, Nakamura M, Lane NE. Effects of inflammation on bone: an update. Curr Opin Rheumatol. 2011 Jul; 23(4):389-95. PMID: 21532485.
      View in: PubMed
    14. Baker-LePain JC, Nakamura M, Shepherd J, von Scheven E. Assessment of bone remodelling in childhood-onset systemic lupus erythematosus. Rheumatology (Oxford). 2011 Mar; 50(3):611-9. PMID: 21098573; PMCID: PMC3042255.
    15. Adapala NS, Barbe MF, Langdon WY, Nakamura M, 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. PMID: 20851882; PMCID: PMC2978603.
    16. Baker-LePain JC, Stone DH, Mattis AN, Nakamura M, Fye KH. Clinical diagnosis of segmental arterial mediolysis: differentiation from vasculitis and other mimics. Arthritis Care Res (Hoboken). 2010 Nov; 62(11):1655-60. PMID: 20662047; PMCID: PMC2974779.
    17. 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. PMID: 20354109; PMCID: PMC2898536.
    18. Li L, Fang CJ, Ryan JC, Niemi EC, Lebrón JA, Björkman PJ, Arase H, Torti FM, Torti SV, Nakamura M, 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. PMID: 20133674; PMCID: PMC2840523.
    19. 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. PMID: 19625651; PMCID: PMC2742169.
    20. Hsieh CL, Koike M, Spusta SC, Niemi EC, Yenari M, Nakamura M, Seaman WE. A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J Neurochem. 2009 May; 109(4):1144-56. PMID: 19302484; PMCID: PMC3087597.
    21. Yao W, Cheng Z, Busse C, Pham A, Nakamura M, 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. PMID: 18512788; PMCID: PMC3892702.
    22. Charles JF, Humphrey MB, Zhao X, Quarles E, Nakamura M, 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. PMID: 18391000; PMCID: PMC2423085.
    23. Wu Y, Humphrey MB, Nakamura M. Osteoclasts - the innate immune cells of the bone. Autoimmunity. 2008 Apr; 41(3):183-94. PMID: 18365831.
      View in: PubMed
    24. Wu Y, Torchia J, Yao W, Lane NE, Lanier LL, Nakamura M, Humphrey MB. Bone microenvironment specific roles of ITAM adapter signaling during bone remodeling induced by acute estrogen-deficiency. PLoS One. 2007 Jul 04; 2(7):e586. PMID: 17611621; PMCID: PMC1895921.
    25. Hamerman JA, Jarjoura JR, Humphrey MB, Nakamura M, 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. PMID: 16887962.
      View in: PubMed
    26. Humphrey MB, Lanier LL, Nakamura M. Role of ITAM-containing adapter proteins and their receptors in the immune system and bone. Immunol Rev. 2005 Dec; 208:50-65. PMID: 16313340.
      View in: PubMed
    27. Humphrey MB, Daws MR, Spusta SC, Niemi EC, Torchia JA, Lanier LL, Seaman WE, Nakamura M. TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. J Bone Miner Res. 2006 Feb; 21(2):237-45. PMID: 16418779.
      View in: PubMed
    28. Chen TT, Li L, Chung DH, Allen CD, Torti SV, Torti FM, Cyster JG, Chen CY, Brodsky FM, Niemi EC, Nakamura M, 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 03; 202(7):955-65. PMID: 16203866; PMCID: PMC2213179.
    29. Lane NE, Yao W, Nakamura M, 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. PMID: 15619670.
      View in: PubMed
    30. Mócsai A, Humphrey MB, Van Ziffle JA, Hu Y, Burghardt A, Spusta SC, Majumdar S, Lanier LL, Lowell CA, Nakamura M. 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. PMID: 15073337; PMCID: PMC395939.
    31. Humphrey MB, Ogasawara K, Yao W, Spusta SC, Daws MR, Lane NE, Lanier LL, Nakamura M. The signaling adapter protein DAP12 regulates multinucleation during osteoclast development. J Bone Miner Res. 2004 Feb; 19(2):224-34. PMID: 14969392.
      View in: PubMed
    32. Chung DH, Humphrey MB, Nakamura M, 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. PMID: 14662855.
      View in: PubMed