University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Mary C. Nakamura, MD

Mary C. Nakamura, MD

Assistant Professor, Department of Medicine, UCSF

Cancer Center Program Memberships

Affiliate Member

Research Summary

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.


Swarthmore College, Swarthmore, PA, B.A., 1981, Biology
Yale University School of Medicine, New Haven, CT, M.D., cum laude, 1986, Medicine
Intern and resident, Department of Internal Medicine, UCSF, San Francisco, CA, 1986-1989
Rheumatology Fellow, Div. Rheumatology, Johns Hopkins U., Baltimore, MD, 1990-1991
Rheumatology Fellow, Div. Rheumatology, UCSF, San Francisco, CA, 1991-1994

Professional Experience

  • 1989-1990
    Clinical Instructor, Acquired Immunodeficiencies Clinic, UCSF, San Francisco, CA
  • 1995-2000
    Adjunct Assistant Prof. Medicine, UCSF, San Francisco, CA
  • 1995-1998
    Director Arthritis Clinic, San Francisco Veterans Affairs Hospital, San Francisco, CA
  • 2000-present
    Assistant Prof. of Medicine, in residence, Dept. of Medicine, Division of Rheumatology, San Francisco Veterans Administration Medical Center

Honors & Awards

  • 1977-1981
    Pacific Regional Scholarship, Swarthmore College
  • 1981
    Phi Beta Kappa, Sigma Xi
  • 1984 and 1985
    Lupus Foundation of America Summer Fellowship
  • 1986
    Louis G. Welt Prize for outstanding medical school thesis
  • 1986
    Janet M. Glasgow Memorial Achievement Citation, American Medical Women's Association for scholastic achievement
  • 1989
    Jeffrey Weingarten Award for Housestaff
  • 2000
    Presidential Early Career Award

Selected Publications

  1. Clark D, Nakamura M, Miclau T, Marcucio R. Effects of Aging on Fracture Healing. Curr Osteoporos Rep. 2017 Dec; 15(6):601-608.
    View on PubMed
  2. Humphrey MB, Nakamura MC. A Comprehensive Review of Immunoreceptor Regulation of Osteoclasts. Clin Rev Allergy Immunol. 2016 Aug; 51(1):48-58.
    View on PubMed
  3. Kim CC, Nakamura MC, Hsieh CL. Brain trauma elicits non-canonical macrophage activation states. J Neuroinflammation. 2016 May 24; 13(1):117.
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  4. Kawabori M, Kacimi R, Kauppinen T, Calosing C, Kim JY, Hsieh CL, Nakamura MC, 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.
    View on PubMed
  5. Hsieh CL, Niemi EC, Wang SH, Lee CC, Bingham D, Zhang J, Cozen ML, Charo I, Huang EJ, Liu J, Nakamura MC. CCR2 deficiency impairs macrophage infiltration and improves cognitive function after traumatic brain injury. J Neurotrauma. 2014 Oct 15; 31(20):1677-88.
    View on PubMed
  6. Charles JF, Nakamura MC. Bone and the innate immune system. Curr Osteoporos Rep. 2014 Mar; 12(1):1-8.
    View on PubMed
  7. 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 on PubMed
  8. Kawabori M, Hokari M, Zheng Z, Kim JY, Calosing C, Hsieh CL, Nakamura MC, 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.
    View on PubMed
  9. 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.
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  10. 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; 122(12):4592-605.
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  11. 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.
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  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 MC, 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.
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  13. Baker-LePain JC, Nakamura MC, Lane NE. Effects of inflammation on bone: an update. Curr Opin Rheumatol. 2011 Jul; 23(4):389-95.
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  14. 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.
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  15. 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.
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  16. 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.
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  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.
    View on PubMed
  18. 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.
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  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.
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  20. 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 on PubMed

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