Research Summary

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.

Research Funding

  • October 1, 2016 - September 30, 2020 - Immune Modulation and Cardiac Remodeling, Principal Investigator. Sponsor: VA, Sponsor Award ID: I01BX002994
  • September 30, 2013 - May 31, 2017 - Effects of Aging on Macrophages and Bone Regeneration, Co-Principal Investigator. Sponsor: NIH/NIA, Sponsor Award ID: R01AG046282
  • October 1, 2009 - September 30, 2013 - DAP12 and ITAM-signals in Osteoclastogenesis, Principal Investigator. Sponsor: VA, Sponsor Award ID: I01BX000615
  • August 1, 2008 - April 30, 2011 - Using VEGF expression in inflammatory arthritis to induce targeted apoptosis, Principal Investigator. Sponsor: NIH/NIAMS, Sponsor Award ID: R21AR056365

Education

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

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. Matsuo K, Lepinski A, Chavez RD, Barruet E, Pereira A, Moody TA, Ton AN, Sharma A, Hellman J, Tomoda K, Nakamura MC, Hsiao EC. ACVR1R206H extends inflammatory responses in human induced pluripotent stem cell-derived macrophages. Bone. 2021 Jul 24; 153:116129.  View on PubMed
  2. Fraenkel L, Bathon JM, England BR, St Clair EW, Arayssi T, Carandang K, Deane KD, Genovese M, Huston KK, Kerr G, Kremer J, Nakamura MC, Russell LA, Singh JA, Smith BJ, Sparks JA, Venkatachalam S, Weinblatt ME, Al-Gibbawi M, Baker JF, Barbour KE, Barton JL, Cappelli L, Chamseddine F, George M, Johnson SR, Kahale L, Karam BS, Khamis AM, Navarro-Millán I, Mirza R, Schwab P, Singh N, Turgunbaev M, Turner AS, Yaacoub S, Akl EA. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2021 07; 73(7):924-939.  View on PubMed
  3. Fraenkel L, Bathon JM, England BR, St Clair EW, Arayssi T, Carandang K, Deane KD, Genovese M, Huston KK, Kerr G, Kremer J, Nakamura MC, Russell LA, Singh JA, Smith BJ, Sparks JA, Venkatachalam S, Weinblatt ME, Al-Gibbawi M, Baker JF, Barbour KE, Barton JL, Cappelli L, Chamseddine F, George M, Johnson SR, Kahale L, Karam BS, Khamis AM, Navarro-Millán I, Mirza R, Schwab P, Singh N, Turgunbaev M, Turner AS, Yaacoub S, Akl EA. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Rheumatol. 2021 07; 73(7):1108-1123.  View on PubMed
  4. Deepak P, Kim W, Paley MA, Yang M, Carvidi AB, El-Qunni AA, Haile A, Huang K, Kinnett B, Liebeskind MJ, Liu Z, McMorrow LE, Paez D, Perantie DC, Schriefer RE, Sides SE, Thapa M, Gergely M, Abushamma S, Klebert M, Mitchell L, Nix D, Graf J, Taylor KE, Chahin S, Ciorba MA, Katz P, Matloubian M, O'Halloran JA, Presti RM, Wu GF, Whelan SPJ, Buchser WJ, Gensler LS, Nakamura MC, Ellebedy AH, Kim AHJ. Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2. medRxiv. 2021 Apr 09.  View on PubMed
  5. Dietz BW, Nakamura MC, Bell MT, Lane NE. Targeting Nerve Growth Factor for Pain Management in Osteoarthritis-Clinical Efficacy and Safety. Rheum Dis Clin North Am. 2021 05; 47(2):181-195.  View on PubMed
  6. Calabrese DR, Aminian E, Mallavia B, Liu F, Cleary SJ, Aguilar OA, Wang P, Singer JP, Hays SR, Golden JA, Kukreja J, Dugger D, Nakamura M, Lanier LL, Looney MR, Greenland JR. Natural killer cells activated through NKG2D mediate lung ischemia-reperfusion injury. J Clin Invest. 2021 02 01; 131(3).  View on PubMed
  7. Vasudevan S, Vásquez JJ, Chen W, Aguilar-Rodriguez B, Niemi EC, Zeng S, Tamaki W, Nakamura MC, Arjomandi M. Lower PDL1, PDL2, and AXL Expression on Lung Myeloid Cells Suggests Inflammatory Bias in Smoking and Chronic Obstructive Pulmonary Disease. Am J Respir Cell Mol Biol. 2020 12; 63(6):780-793.  View on PubMed
  8. Wilfong EM, Croze R, Fang X, Schwede M, Niemi E, López GY, Lee JW, Nakamura MC, Matthay MA. 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.  View on PubMed
  9. 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. Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation. Nat Immunol. 2020 04; 21(4):422-433.  View on PubMed
  10. Clark D, Brazina S, Yang F, Hu D, Hsieh CL, Niemi EC, Miclau T, Nakamura MC, Marcucio R. Age-related changes to macrophages are detrimental to fracture healing in mice. Aging Cell. 2020 03; 19(3):e13112.  View on PubMed
  11. Wang L, Roth T, Nakamura MC, Nissenson RA. Female-Specific Role of Progranulin to Suppress Bone Formation. Endocrinology. 2019 09 01; 160(9):2024-2037.  View on PubMed
  12. Nakamura MC. Osteoimmunology: entwined regulation of integrated systems. Semin Immunopathol. 2019 09; 41(5):547-549.  View on PubMed
  13. Barruet E, Morales BM, Cain CJ, Ton AN, Wentworth KL, Chan TV, Moody TA, Haks MC, Ottenhoff TH, Hellman J, Nakamura MC, Hsiao EC. NF-?B/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification. JCI Insight. 2018 11 15; 3(22).  View on PubMed
  14. Clark D, Nakamura M, Miclau T, Marcucio R. Effects of Aging on Fracture Healing. Curr Osteoporos Rep. 2017 12; 15(6):601-608.  View on PubMed
  15. 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
  16. Kim CC, Nakamura MC, Hsieh CL. Brain trauma elicits non-canonical macrophage activation states. J Neuroinflammation. 2016 05 24; 13(1):117.  View on PubMed
  17. 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
  18. 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
  19. Charles JF, Nakamura MC. Bone and the innate immune system. Curr Osteoporos Rep. 2014 Mar; 12(1):1-8.  View on PubMed
  20. 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

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