Mary Nakamura, MD

Professor

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.
Education
2018 - Diversity, Equity, and Inclusion Champion Training, University of California
Fellowship, 1994 - Rheumatology, University of California, San Francisco
Fellowship, 1991 - Rheumatology, Johns Hopkins University
Residency, 1989 - Internal Medicine, University of California, San Francisco
MD, 1986 - School of Medicine, Yale University
BA, 1981 - Biology, Swarthmore College
Honors and Awards
  • Associate Director PREMIER: Precision Medicine in Rheumtology p30 Center, UCSF, 2016
  • Excellence in Teaching Award in medical education, The Haile Debas Academy of Medical Educators, UCSF, 2015
  • Henry Kunkel Young Investigator Award, American College of Rheumatology, 2005
  • Ira M. Goldstein Award for Outstanding Teaching in Rheumatology, UCSF, 2004
  • Presidential Early Career Award, President of US, 2000
  • VA Career Development Award, VA, 1998
  • Physician Scientist Development Award, ACR, 1993
  • Jeffrey Weingarten Award for Housestaff, UCSF, 1989
  • J.M. Glasgow Memorial AMWA scholastic citation, Yale Medical School, 1986
  • Louis G. Welt Prize for medical school thesis, Yale Medical School, 1986
Websites
Publications
  1. 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. 2021. PMID: 34551293


  2. 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. 2021. PMID: 34461029


  3. 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. 2021. PMID: 34311122


  4. 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. 2021. PMID: 34101387


  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. 2021. PMID: 34101376


  6. 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. 2020. PMID: 33290276


  7. Vasudevan S, Vásquez JJ, Chen W, Aguilar-Rodriguez B, Niemi EC, Zeng S, Tamaki W, Nakamura MC, Arjomandi M. Lower PDL1/2 and AXL Expression on Lung Myeloid Cells Suggests Inflammatory Bias in Smoking and COPD. 2020. PMID: 32915645


  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. 2020. PMID: 33021986


  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. 2020. PMID: 32205880


  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. 2020. PMID: 32096907


  11. Wang L, Roth T, Nakamura MC, Nissenson RA. Female-Specific Role of Progranulin to Suppress Bone Formation. 2019. PMID: 31237618


  12. 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. 2018. PMID: 30429363


  13. Clark D, Nakamura M, Miclau T, Marcucio R. Effects of Aging on Fracture Healing. Volume 15 of Issue 6. 2017. PMID: 29143915


  14. Humphrey MB, Nakamura MC. A Comprehensive Review of Immunoreceptor Regulation of Osteoclasts. Volume 51 of Issue 1. 2016. PMID: 26573914


  15. Kim CC, Nakamura MC, Hsieh CL. Brain trauma elicits non-canonical macrophage activation states. Volume 13 of Issue 1. 2016. PMID: 27220367


  16. 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. Volume 35 of Issue 8. 2015. PMID: 25716838


  17. 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. Volume 31 of Issue 20. 2014. PMID: 24806994


  18. Charles JF, Nakamura MC. Bone and the innate immune system. Volume 12 of Issue 1. 2014. PMID: 24500569


  19. Nakamura MC. CIITA: a master regulator of adaptive immunity shows its innate side in the bone. Volume 29 of Issue 2. 2014. PMID: 24343972


  20. 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. Volume 3 of Issue 4. 2013. PMID: 24380032


  21. 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. Volume 43 of Issue 8. 2013. PMID: 23630120


  22. Charles JF, Hsu LY, Niemi EC, Weiss A, Aliprantis AO, Nakamura MC. Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function. Volume 122 of Issue 12. 2012. PMID: 23114597


  23. 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. Volume 120 of Issue 15. 2012. PMID: 22923495


  24. 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. Volume 12 of Issue 12. 2011. PMID: 22019834


  25. Baker-LePain JC, Nakamura MC, Lane NE. Effects of inflammation on bone: an update. Volume 23 of Issue 4. 2011. PMID: 21532485


  26. Baker-LePain JC, Nakamura MC, Shepherd J, von Scheven E. Assessment of bone remodelling in childhood-onset systemic lupus erythematosus. Volume 50 of Issue 3. 2010. PMID: 21098573


  27. 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. Volume 285 of Issue 47. 2010. PMID: 20851882


  28. Baker-LePain JC, Stone DH, Mattis AN, Nakamura MC, Fye KH. Clinical diagnosis of segmental arterial mediolysis: differentiation from vasculitis and other mimics. Volume 62 of Issue 11. 2010. PMID: 20662047


  29. 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. Volume 3 of Issue 7-8. 2010. PMID: 20354109


  30. 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. Volume 107 of Issue 8. 2010. PMID: 20133674


  31. 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. Volume 183 of Issue 4. 2009. PMID: 19625651


  32. 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. Volume 109 of Issue 4. 2009. PMID: 19302484


  33. Charles JF, Humphrey MB, Zhao X, Quarles E, Nakamura MC, Aderem A, Seaman WE, Smith KD. The innate immune response to Salmonella enterica serovar Typhimurium by macrophages is dependent on TREM2-DAP12. Volume 76 of Issue 6. 2008. PMID: 18391000


  34. Wu Y, Humphrey MB, Nakamura MC. Osteoclasts - the innate immune cells of the bone. Volume 41 of Issue 3. 2008. PMID: 18365831


  35. Wu Y, Torchia J, Yao W, Lane NE, Lanier LL, Nakamura MC, Humphrey MB. Bone microenvironment specific roles of ITAM adapter signaling during bone remodeling induced by acute estrogen-deficiency. Volume 2 of Issue 7. 2007. PMID: 17611621


  36. Hamerman JA, Jarjoura JR, Humphrey MB, Nakamura MC, Seaman WE, Lanier LL. Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12. Volume 177 of Issue 4. 2006. PMID: 16887962


  37. Humphrey MB, Lanier LL, Nakamura MC. Role of ITAM-containing adapter proteins and their receptors in the immune system and bone. Volume 208. 2005. PMID: 16313340


  38. Humphrey MB, Daws MR, Spusta SC, Niemi EC, Torchia JA, Lanier LL, Seaman WE, Nakamura MC. TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function. Volume 21 of Issue 2. 2005. PMID: 16418779


  39. 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. TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis. Volume 202 of Issue 7. 2005. PMID: 16203866


  40. Lane NE, Yao W, Nakamura MC, Humphrey MB, Kimmel D, Huang X, Sheppard D, Ross FP, Teitelbaum SL. Mice lacking the integrin beta5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state. Volume 20 of Issue 1. 2004. PMID: 15619670


  41. Mócsai A, Humphrey MB, Van Ziffle JA, Hu Y, Burghardt A, Spusta SC, Majumdar S, Lanier LL, Lowell CA, Nakamura MC. The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase. Volume 101 of Issue 16. 2004. PMID: 15073337


  42. Humphrey MB, Ogasawara K, Yao W, Spusta SC, Daws MR, Lane NE, Lanier LL, Nakamura MC. The signaling adapter protein DAP12 regulates multinucleation during osteoclast development. Volume 19 of Issue 2. 2003. PMID: 14969392


  43. Chung DH, Humphrey MB, Nakamura MC, Ginzinger DG, Seaman WE, Daws MR. CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation. Volume 171 of Issue 12. 2003. PMID: 14662855