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. Calabrese DR, Aminian E, Mallavia B, Liu F, Cleary SJ, Aguilar OA, Wang P, Hoover J, Singer JP, Hays SR, Golden JA, Kukreja J, Dugger DT, Nakamura M, Lanier LL, Looney MR, Greenland JR Natural killer cells activated through NKG2D mediate lung ischemia-reperfusion injury.  View on PubMed
  2. 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.  View on PubMed
  3. 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.  View on PubMed
  4. 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.  View on PubMed
  5. 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.  View on PubMed
  6. Wang L, Roth T, Nakamura MC, Nissenson RA Female-Specific Role of Progranulin to Suppress Bone Formation.  View on PubMed
  7. Nakamura MC Osteoimmunology: entwined regulation of integrated systems.  View on PubMed
  8. 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.  View on PubMed
  9. Clark D, Nakamura M, Miclau T, Marcucio R Effects of Aging on Fracture Healing.  View on PubMed
  10. Humphrey MB, Nakamura MC A Comprehensive Review of Immunoreceptor Regulation of Osteoclasts.  View on PubMed
  11. Kim CC, Nakamura MC, Hsieh CL Brain trauma elicits non-canonical macrophage activation states.  View on PubMed
  12. 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.  View on PubMed
  13. 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.  View on PubMed
  14. Charles JF, Nakamura MC Bone and the innate immune system.  View on PubMed
  15. Nakamura MC CIITA: a master regulator of adaptive immunity shows its innate side in the bone.  View on PubMed
  16. 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.  View on PubMed
  17. 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.  View on PubMed
  18. Charles JF, Hsu LY, Niemi EC, Weiss A, Aliprantis AO, Nakamura MC Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function.  View on PubMed
  19. 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.  View on PubMed
  20. 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.  View on PubMed

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