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Mary Nakamura, MD

Title(s)Professor, Medicine
SchoolSchool of Medicine
Address533 Parnassus Avenue
San Francisco CA 94117
Phone415-750-2104 ext. 3458
ORCID ORCID Icon0000-0001-8127-9426 Additional info
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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
    University of California, San Francisco, CA2018Diversity, Equity, and Inclusion Champion Training
    Collapse Awards and Honors
    UCSF 2016Associate Director PREMIER: Precision Medicine in Rheumtology p30 Center
    UCSF2015Excellence in Teaching Award in medical education, The Haile Debas Academy of Medical Educators
    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
    Mary Nakamura received her B.A. from Swarthmore College, her M.D. from Yale and trained in internal medicine at the University of California, San Francisco. She completed her rheumatology training at Johns Hopkins and UCSF. She did her post doctoral work at UCSF under the mentorship of Bill Seaman. She is a basic-translational researcher focused on studies in the field of osteoimmunology. She leads the Rheumatoid Arthritis Clinic at UCSF Parnassus and is a clinical attending at the SF VA HCS.

    Research Statement
    My research has focused on the study of cells in the innate immune system. We have focused on receptor regulation of NK cells, macrophages and osteoclasts and the roles these cells play in disease pathology and tissue repair. We were one the early investigative groups focusing work in the field of Osteoimmunology, 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. Our studies demonstrated that innate immune receptors that utilize ITAM or immunoreceptor tyrosine based activation motif signals are critical regulators of osteoclast development and function, during normal bone development and homeostasis and we demonstrated that mice deficient in the ITAM adapter signaling chains DAP12 and FcRgamma are severely 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 work in my laboratory on osteoimmunology since the role of innate immune receptor regulation in the bone is 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 integrates my research interests with my clinical subspecialty work. Our studies in the role of immune cells in bone repair have led us to collaborative studies examining the role of innate immune cells in other types of tissue repair including traumatic brain injury, ischemic stroke and myocardial infarction.

    Our work has primarily been focused in mouse models of disease, but we are also involved in studies of human osteoclasts in vitro and are beginning translational studies with rheumatic disease 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 - May 31, 2017
    Role: Co-Principal Investigator
    DAP12 and ITAM-signals in Osteoclastogenesis
    VA I01BX000615Oct 1, 2009 - Sep 30, 2013
    Role: Principal Investigator
    Using VEGF expression in inflammatory arthritis to induce targeted apoptosis
    NIH/NIAMS R21AR056365Aug 1, 2008 - Apr 30, 2011
    Role: Principal Investigator
    DAP-12 ASSOCIATED RECEPTORS IN OSTEOCLASTS
    NIH/NIAMS R01AR050038Aug 1, 2004 - Jun 30, 2010
    Role: Principal Investigator
    LIGANDS FOR NKR P1--A RECEPTOR ON NATURAL KILLER CELLS
    NIH/NIAMS K11AR001927May 1, 1994 - Jun 30, 2000
    Role: Principal Investigator

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    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. to make corrections and additions.
    Newest   |   Oldest   |   Most Cited   |   Most Discussed   |   Timeline   |   Field Summary   |   Plain Text
    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Proinflammatory cytokines and ARDS pulmonary edema fluid induce CD40 on human mesenchymal stromal cells-A potential mechanism for immune modulation. PLoS One. 2020; 15(10):e0240319. Wilfong EM, Croze R, Fang X, Schwede M, Niemi E, López GY, Lee JW, Nakamura MC, Matthay MA. PMID: 33021986.
      View in: PubMed   Mentions:    Fields:    
    2. Lower PDL1/2 and AXL Expression on Lung Myeloid Cells Suggests Inflammatory Bias in Smoking and COPD. Am J Respir Cell Mol Biol. 2020 Sep 11. Vasudevan S, Vásquez JJ, Chen W, Aguilar-Rodriguez B, Niemi EC, Zeng S, Tamaki W, Nakamura MC, Arjomandi M. PMID: 32915645.
      View in: PubMed   Mentions:    Fields:    
    3. Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation. Nat Immunol. 2020 04; 21(4):422-433. Razani B, Whang MI, Kim FS, Nakamura MC, Sun X, Advincula R, Turnbaugh JA, Pendse M, Tanbun P, Achacoso P, Turnbaugh PJ, Malynn BA, Ma A. PMID: 32205880.
      View in: PubMed   Mentions: 5     Fields:    Translation:AnimalsCells
    4. Age-related changes to macrophages are detrimental to fracture healing in mice. Aging Cell. 2020 03; 19(3):e13112. Clark D, Brazina S, Yang F, Hu D, Hsieh CL, Niemi EC, Miclau T, Nakamura MC, Marcucio R. PMID: 32096907.
      View in: PubMed   Mentions:    Fields:    
    5. Female-Specific Role of Progranulin to Suppress Bone Formation. Endocrinology. 2019 09 01; 160(9):2024-2037. Wang L, Roth T, Nakamura MC, Nissenson RA. PMID: 31237618.
      View in: PubMed   Mentions: 1     Fields:    Translation:Animals
    6. Osteoimmunology: entwined regulation of integrated systems. Semin Immunopathol. 2019 09; 41(5):547-549. Nakamura MC. PMID: 31654179.
      View in: PubMed   Mentions:    Fields:    Translation:HumansAnimalsCells
    7. NF-κB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification. JCI Insight. 2018 11 15; 3(22). Barruet E, Morales BM, Cain CJ, Ton AN, Wentworth KL, Chan TV, Moody TA, Haks MC, Ottenhoff TH, Hellman J, Nakamura MC, Hsiao EC. PMID: 30429363.
      View in: PubMed   Mentions: 7     Fields:    Translation:HumansCells
    8. Effects of Aging on Fracture Healing. Curr Osteoporos Rep. 2017 12; 15(6):601-608. Clark D, Nakamura M, Miclau T, Marcucio R. PMID: 29143915.
      View in: PubMed   Mentions: 13     Fields:    Translation:HumansCells
    9. A Comprehensive Review of Immunoreceptor Regulation of Osteoclasts. Clin Rev Allergy Immunol. 2016 Aug; 51(1):48-58. Humphrey MB, Nakamura MC. PMID: 26573914.
      View in: PubMed   Mentions: 15     Fields:    Translation:HumansAnimalsCells
    10. Brain trauma elicits non-canonical macrophage activation states. J Neuroinflammation. 2016 05 24; 13(1):117. Kim CC, Nakamura MC, Hsieh CL. PMID: 27220367.
      View in: PubMed   Mentions: 37     Fields:    Translation:AnimalsCells
    11. 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. Kawabori M, Kacimi R, Kauppinen T, Calosing C, Kim JY, Hsieh CL, Nakamura MC, Yenari MA. PMID: 25716838.
      View in: PubMed   Mentions: 70     Fields:    Translation:AnimalsCells
    12. CCR2 deficiency impairs macrophage infiltration and improves cognitive function after traumatic brain injury. J Neurotrauma. 2014 Oct 15; 31(20):1677-88. Hsieh CL, Niemi EC, Wang SH, Lee CC, Bingham D, Zhang J, Cozen ML, Charo I, Huang EJ, Liu J, Nakamura MC. PMID: 24806994.
      View in: PubMed   Mentions: 52     Fields:    Translation:AnimalsCells
    13. Bone and the innate immune system. Curr Osteoporos Rep. 2014 Mar; 12(1):1-8. Charles JF, Nakamura MC. PMID: 24500569.
      View in: PubMed   Mentions: 12     Fields:    Translation:HumansCells
    14. CIITA: a master regulator of adaptive immunity shows its innate side in the bone. J Bone Miner Res. 2014 Feb; 29(2):287-9. Nakamura MC. PMID: 24343972.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    15. 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. Kawabori M, Hokari M, Zheng Z, Kim JY, Calosing C, Hsieh CL, Nakamura MC, Yenari MA. PMID: 24380032.
      View in: PubMed   Mentions: 13     Fields:    
    16. Traumatic brain injury induces macrophage subsets in the brain. Eur J Immunol. 2013 Aug; 43(8):2010-22. Hsieh CL, Kim CC, Ryba BE, Niemi EC, Bando JK, Locksley RM, Liu J, Nakamura MC, Seaman WE. PMID: 23630120.
      View in: PubMed   Mentions: 50     Fields:    Translation:AnimalsCells
    17. Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function. J Clin Invest. 2012 Dec; 122(12):4592-605. Charles JF, Hsu LY, Niemi EC, Weiss A, Aliprantis AO, Nakamura MC. PMID: 23114597.
      View in: PubMed   Mentions: 51     Fields:    Translation:HumansAnimalsCells
    18. PSTPIP2 deficiency in mice causes osteopenia and increased differentiation of multipotent myeloid precursors into osteoclasts. Blood. 2012 Oct 11; 120(15):3126-35. Chitu V, Nacu V, Charles JF, Henne WM, McMahon HT, Nandi S, Ketchum H, Harris R, Nakamura MC, Stanley ER. PMID: 22923495.
      View in: PubMed   Mentions: 26     Fields:    Translation:AnimalsCells
    19. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis. Nat Immunol. 2011 Oct 23; 12(12):1184-93. 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. PMID: 22019834.
      View in: PubMed   Mentions: 100     Fields:    Translation:HumansAnimalsCells
    20. Effects of inflammation on bone: an update. Curr Opin Rheumatol. 2011 Jul; 23(4):389-95. Baker-LePain JC, Nakamura MC, Lane NE. PMID: 21532485.
      View in: PubMed   Mentions: 17     Fields:    Translation:HumansCells
    21. Assessment of bone remodelling in childhood-onset systemic lupus erythematosus. Rheumatology (Oxford). 2011 Mar; 50(3):611-9. Baker-LePain JC, Nakamura MC, Shepherd J, von Scheven E. PMID: 21098573.
      View in: PubMed   Mentions: 5     Fields:    Translation:Humans
    22. 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. Adapala NS, Barbe MF, Langdon WY, Nakamura MC, Tsygankov AY, Sanjay A. PMID: 20851882.
      View in: PubMed   Mentions: 21     Fields:    Translation:AnimalsCells
    23. Clinical diagnosis of segmental arterial mediolysis: differentiation from vasculitis and other mimics. Arthritis Care Res (Hoboken). 2010 Nov; 62(11):1655-60. Baker-LePain JC, Stone DH, Mattis AN, Nakamura MC, Fye KH. PMID: 20662047.
      View in: PubMed   Mentions: 25     Fields:    Translation:Humans
    24. Multiple roles for CCR2 during fracture healing. Dis Model Mech. 2010 Jul-Aug; 3(7-8):451-8. Xing Z, Lu C, Hu D, Yu YY, Wang X, Colnot C, Nakamura M, Wu Y, Miclau T, Marcucio RS. PMID: 20354109.
      View in: PubMed   Mentions: 53     Fields:    Translation:AnimalsCells
    25. 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. Li L, Fang CJ, Ryan JC, Niemi EC, Lebrón JA, Björkman PJ, Arase H, Torti FM, Torti SV, Nakamura MC, Seaman WE. PMID: 20133674.
      View in: PubMed   Mentions: 86     Fields:    Translation:HumansCells
    26. 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. Park-Min KH, Ji JD, Antoniv T, Reid AC, Silver RB, Humphrey MB, Nakamura M, Ivashkiv LB. PMID: 19625651.
      View in: PubMed   Mentions: 38     Fields:    Translation:HumansAnimalsCells
    27. A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J Neurochem. 2009 May; 109(4):1144-56. Hsieh CL, Koike M, Spusta SC, Niemi EC, Yenari M, Nakamura MC, Seaman WE. PMID: 19302484.
      View in: PubMed   Mentions: 140     Fields:    Translation:AnimalsCells
    28. 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. Yao W, Cheng Z, Busse C, Pham A, Nakamura MC, Lane NE. PMID: 18512788.
      View in: PubMed   Mentions: 74     Fields:    Translation:AnimalsCells
    29. The innate immune response to Salmonella enterica serovar Typhimurium by macrophages is dependent on TREM2-DAP12. Infect Immun. 2008 Jun; 76(6):2439-47. Charles JF, Humphrey MB, Zhao X, Quarles E, Nakamura MC, Aderem A, Seaman WE, Smith KD. PMID: 18391000.
      View in: PubMed   Mentions: 18     Fields:    Translation:AnimalsCells
    30. Osteoclasts - the innate immune cells of the bone. Autoimmunity. 2008 Apr; 41(3):183-94. Wu Y, Humphrey MB, Nakamura MC. PMID: 18365831.
      View in: PubMed   Mentions: 16     Fields:    Translation:HumansAnimalsCells
    31. Bone microenvironment specific roles of ITAM adapter signaling during bone remodeling induced by acute estrogen-deficiency. PLoS One. 2007 Jul 04; 2(7):e586. Wu Y, Torchia J, Yao W, Lane NE, Lanier LL, Nakamura MC, Humphrey MB. PMID: 17611621.
      View in: PubMed   Mentions: 23     Fields:    Translation:AnimalsCells
    32. 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. Hamerman JA, Jarjoura JR, Humphrey MB, Nakamura MC, Seaman WE, Lanier LL. PMID: 16887962.
      View in: PubMed   Mentions: 156     Fields:    Translation:AnimalsCells
    33. Role of ITAM-containing adapter proteins and their receptors in the immune system and bone. Immunol Rev. 2005 Dec; 208:50-65. Humphrey MB, Lanier LL, Nakamura MC. PMID: 16313340.
      View in: PubMed   Mentions: 85     Fields:    Translation:HumansAnimalsCells
    34. TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. J Bone Miner Res. 2006 Feb; 21(2):237-45. Humphrey MB, Daws MR, Spusta SC, Niemi EC, Torchia JA, Lanier LL, Seaman WE, Nakamura MC. PMID: 16418779.
      View in: PubMed   Mentions: 55     Fields:    Translation:AnimalsCells
    35. 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. 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. PMID: 16203866.
      View in: PubMed   Mentions: 73     Fields:    Translation:AnimalsCells
    36. 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. Lane NE, Yao W, Nakamura MC, Humphrey MB, Kimmel D, Huang X, Sheppard D, Ross FP, Teitelbaum SL. PMID: 15619670.
      View in: PubMed   Mentions: 24     Fields:    Translation:AnimalsCells
    37. 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. Mócsai A, Humphrey MB, Van Ziffle JA, Hu Y, Burghardt A, Spusta SC, Majumdar S, Lanier LL, Lowell CA, Nakamura MC. PMID: 15073337.
      View in: PubMed   Mentions: 161     Fields:    Translation:AnimalsCells
    38. The signaling adapter protein DAP12 regulates multinucleation during osteoclast development. J Bone Miner Res. 2004 Feb; 19(2):224-34. Humphrey MB, Ogasawara K, Yao W, Spusta SC, Daws MR, Lane NE, Lanier LL, Nakamura MC. PMID: 14969392.
      View in: PubMed   Mentions: 43     Fields:    Translation:AnimalsCells
    39. CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation. J Immunol. 2003 Dec 15; 171(12):6541-8. Chung DH, Humphrey MB, Nakamura MC, Ginzinger DG, Seaman WE, Daws MR. PMID: 14662855.
      View in: PubMed   Mentions: 47     Fields:    Translation:AnimalsCells
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