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
I am a clinical rheumatologist who has done basic research in the area of innate immune receptors for the past 29 years. I was a postdoctoral fellow with Bill Seaman focused studies of innate receptor regulation of Natural Killer cells. For the last 21 years I have focused much of our work on the role of innate immune receptors on osteoclasts and innate immune regulation of normal and pathological bone turnover. I led one of the early groups focusing research in the area of osteoimmunology and was one of the first to identify the role of innate receptors in osteoclast differentiation and function. Osteoimmunology, is defined as a cross disciplinary field to integrate studies of the immune system and bone and the interactions between these systems which is a topic integral to the clinical field of rheumatology and has furthered my goal of integrating my research with my clinical work. Recently we have also focused work on innate receptors, macrophages and tissue regeneration examining these cells and their function in bone, brain and cardiac injury. Our work has demonstrated roles for macrophages in tissue regeneration and we are examining effects of age and autoimmunity on macrophage phenotype and function which may contribute to defective tissue repair. I have worked with a number of young investigators to enhance their studies by providing key guidance and experiments to examine myeloid cells, bone and/or immune cells in the bone for a number of advanced trainee projects over the past few years.

I am also dedicated to promoting basic-translational work in rheumatologic and autoimmune disease at UCSF. I partnered with Lindsey Criswell to develop PREMIER, an NIH p30 Center for the Advancement of Precision Medicine in Rheumatology a number of years ago. Following her departure to NIAMS, I assumed directorship of the Center and I successfully applied to renew this center grant last year. I continue to lead this effort to integrate research focused on patient cohorts using clinical informatics and state of the art molecular phenotyping using patient samples to advance our understanding of rheumatologic disease heterogeneity, outcomes and therapeutic responses. As part of one of PREMIER's efforts, I led a study of SARS CoV2 vaccine response in autoimmune and autoinflammatory disease patients as soon as the vaccination effort rolled out and partnered with colleagues at Washington University in St. Louis to expand the cohort. We managed to publish this work about 8 months after vaccine administration began.

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. Kim AHJ, Nakamura MC. COVID-19 Breakthrough Infection Among Immunocompromised Persons. JAMA Intern Med. 2021 Dec 28.  View on PubMed
  2. Somebang K, Rudolph J, Imhof I, Li L, Niemi EC, Shigenaga J, Tran H, Gill TM, Lo I, Zabel BA, Schmajuk G, Wipke BT, Gyoneva S, Jandreski L, Craft M, Benedetto G, Plowey ED, Charo I, Campbell J, Ye CJ, Panter SS, Nakamura MC, Eckalbar W, Hsieh CL. CCR2 deficiency alters activation of microglia subsets in traumatic brain injury. Cell Rep. 2021 Sep 21; 36(12):109727.  View on PubMed
  3. Deepak P, Kim W, Paley MA, Yang M, Carvidi AB, Demissie EG, El-Qunni AA, Haile A, Huang K, Kinnett B, Liebeskind MJ, Liu Z, McMorrow LE, Paez D, Pawar N, Perantie DC, Schriefer RE, Sides SE, Thapa M, Gergely M, Abushamma S, Akuse 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. Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2 : A Prospective Cohort Study. Ann Intern Med. 2021 Aug 31.  View on PubMed
  4. 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 Dec; 153:116129.  View on PubMed
  5. 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
  6. 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
  7. Vallania F, Zisman L, Macaubas C, Hung SC, Rajasekaran N, Mason S, Graf J, Nakamura M, Mellins ED, Khatri P. Multicohort Analysis Identifies Monocyte Gene Signatures to Accurately Monitor Subset-Specific Changes in Human Diseases. Front Immunol. 2021; 12:659255.  View on PubMed
  8. Clark D, Halpern B, Miclau T, Nakamura M, Kapila Y, Marcucio R. The Contribution of Macrophages in Old Mice to Periodontal Disease. J Dent Res. 2021 Apr 27; 220345211009463.  View on PubMed
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. Nakamura MC. Osteoimmunology: entwined regulation of integrated systems. Semin Immunopathol. 2019 09; 41(5):547-549.  View on PubMed
  18. 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-κB/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification. JCI Insight. 2018 11 15; 3(22).  View on PubMed
  19. 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
  20. 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

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