Mary Nakamura, MD

PROF IN RES-HCOMP

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.

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
  • Director PREMIER: Precision Medicine in Rheumtology p30 Center, UCSF, 2020
  • Associate Director PREMIER: Precision Medicine in Rheumtology p30 Center, UCSF, 2016-2020
  • 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. Binvignat M, Miao BY, Wibrand C, Yang MM, Rychkov D, Flynn E, Nititham J, Tamaki W, Khan U, Carvidi A, Krueger M, Niemi EC, Sun Y, Fragiadakis GK, Sellam J, Mariotti-Ferrandiz E, Klatzmann D, Gross AJ, Ye CJ, Butte AJ, Criswell LA, Nakamura MC, Sirota M. Single-cell RNA-seq analysis reveals cell subsets and gene signatures associated with Rheumatoid Arthritis Disease Activity. JCI insight 2024. PMID: 38954480


  2. Clark D, Brazina S, Miclau T, Park S, Hsieh CL, Nakamura M, Marcucio R. Age-related changes to macrophage subpopulations and TREM2 dysregulation characterize attenuated fracture healing in old mice. Aging cell 2024. PMID: 38825965


  3. Nasrallah C, Wilson C, Hamblin A, Young C, Jacobsohn L, Nakamura MC, Gross A, Matloubian M, Ashouri J, Yazdany J, Schmajuk G. Using the technology acceptance model to assess clinician perceptions and experiences with a rheumatoid arthritis outcomes dashboard: qualitative study. BMC medical informatics and decision making 2024. PMID: 38802865


  4. Adams C, Nair N, Plant D, Verstappen SMM, Quach HL, Quach DL, Carvidi A, Nititham J, Nakamura M, Graf J, Barton A, Criswell LA, Barcellos LF. Identification of cell-specific differential DNA methylation associated with methotrexate treatment response in rheumatoid arthritis. Arthritis & rheumatology (Hoboken, N.J.) 2023. PMID: 36716083


  5. Pawar N, Taylor KE, Yang M, Deepak P, Kim W, Paley MA, Matloubian M, Carvidi A, Ciorba MA, Demissie E, El-Qunni A, Huang K, Kinnett B, McMorrow LE, Paez D, Poole M, Rose A, Schriefer RE, Kim AHJ, Nakamura M, Katz P, Gensler LS. Sleep disturbance improves with SARS-COV2 vaccinations in patients with Chronic Inflammatory Disease. Arthritis care & research 2022. PMID: 36479599


  6. Greene SE, Huang Y, Kim W, Liebeskind MJ, Chandrasekaran V, Liu Z, Deepak P, Paley MA, Lew D, Yang M, Matloubian M, Gensler LS, Nakamura MC, O'Hallaran JA, Presti RM, Whelan SPJ, Buchser WJ, Kim AHJ, Weil GJ. A simple point-of-care assay accurately detects anti-spike antibodies after SARS-CoV-2 vaccination. Journal of clinical virology plus 2023. PMID: 36644774


  7. Clark D, Doelling J, Hu D, Miclau T, Nakamura M, Marcucio R. Age-related decrease in periostin expression may be associated with attenuated fracture healing in old mice. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2022. PMID: 36058631


  8. Yang MM, Taylor KE, Paez D, Carividi A, Demissie E, Pawar N, El-Qunni AA, McMorrow LE, Schriefer RE, Huang K, Kinnett B, Klebert M, Haile A, O'Halloran JA, Presti RM, Kim W, Ellebedy AH, Ciorba MA, Paley MA, Deepak P, Kim AHJ, Katz P, Matloubian M, Nakamura M, Gensler LS. Reactogenicity of the mRNA SARS-CoV-2 Vaccines Associates with Immunogenicity in Patients with Autoimmune and Inflammatory Disease. 2022. PMID: 35412029


  9. Patterson SL, Sun S, Rychkov D, Katz P, Tsitsiklis A, Nakamura MC, Serpa PH, Langelier CR, Sirota M. Physical Activity Associates with Lower Systemic Inflammatory Gene Expression in Rheumatoid Arthritis. The Journal of rheumatology 2022. PMID: 35777820


  10. Matsuo K, Lepinski A, Chavez RD, Barruet E, Pereira A, Moody TA, Ton AN, Sharma A, Hellman J, Tomoda K, Nakamura MC, Hsiao EC. Corrigendum to "ACVR1R206H extends inflammatory responses in human induced pluripotent stem cell-derived macrophages" [Bone. 153 2021 Dec; 116129. doi:10.1016/j.bone.2021.116129. Epub 2021 Jul 24. PMID: 34311122]. 2022. PMID: 35241401


  11. Kim AHJ, Nakamura MC. COVID-19 Breakthrough Infection Among Immunocompromised Persons. 2021. PMID: 34962552


  12. 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 reports 2021. PMID: 34551293


  13. 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. Annals of internal medicine 2021. PMID: 34461029


  14. 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. PMID: 34311122


  15. 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


  16. 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


  17. 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. 2021. PMID: 34054824


  18. Clark D, Halpern B, Miclau T, Nakamura M, Kapila Y, Marcucio R. The Contribution of Macrophages in Old Mice to Periodontal Disease. 2021. PMID: 33906501


  19. . Glucocorticoids and B Cell Depleting Agents Substantially Impair Immunogenicity of mRNA Vaccines to SARS-CoV-2. medRxiv : the preprint server for health sciences 2021. PMID: 33851176


  20. Dietz BW, Nakamura MC, Bell MT, Lane NE. Targeting Nerve Growth Factor for Pain Management in Osteoarthritis-Clinical Efficacy and Safety. 2021. PMID: 33781489


  21. 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. The Journal of clinical investigation 2021. PMID: 33290276


  22. 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. American journal of respiratory cell and molecular biology 2020. PMID: 32915645


  23. 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. PMID: 33021986


  24. 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. Nature immunology 2020. PMID: 32205880


  25. 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. PMID: 32096907


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


  27. Nakamura MC. Osteoimmunology: entwined regulation of integrated systems. Seminars in immunopathology 2019. PMID: 31654179


  28. 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. PMID: 30429363


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


  30. Humphrey MB, Nakamura MC. A Comprehensive Review of Immunoreceptor Regulation of Osteoclasts. Volume 51 of Issue 1. Clinical reviews in allergy & immunology 2016. PMID: 26573914


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


  32. 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. The Journal of neuroscience : the official journal of the Society for Neuroscience 2015. PMID: 25716838


  33. 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. Journal of neurotrauma 2014. PMID: 24806994


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


  35. Nakamura MC. CIITA: a master regulator of adaptive immunity shows its innate side in the bone. Volume 29 of Issue 2. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2014. PMID: 24343972


  36. 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. Therapeutic hypothermia and temperature management 2013. PMID: 24380032


  37. 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. European journal of immunology 2013. PMID: 23630120


  38. 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. The Journal of clinical investigation 2012. PMID: 23114597


  39. 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. Blood 2012. PMID: 22923495


  40. 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. Nature immunology 2011. PMID: 22019834


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


  42. 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. Rheumatology (Oxford, England) 2010. PMID: 21098573


  43. 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. The Journal of biological chemistry 2010. PMID: 20851882


  44. 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. Arthritis care & research 2010. PMID: 20662047


  45. 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. Disease models & mechanisms 2010. PMID: 20354109


  46. 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. Proceedings of the National Academy of Sciences of the United States of America 2010. PMID: 20133674


  47. 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. Journal of immunology (Baltimore, Md. : 1950) 2009. PMID: 19625651


  48. 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. Journal of neurochemistry 2009. PMID: 19302484


  49. Yao W, Cheng Z, Busse C, Pham A, Nakamura MC, Lane NE. 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. Volume 58 of Issue 6. Arthritis and rheumatism 2008. PMID: 18512788


  50. 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. Infection and immunity 2008. PMID: 18391000


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


  52. 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. PloS one 2007. PMID: 17611621


  53. 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. Journal of immunology (Baltimore, Md. : 1950) 2006. PMID: 16887962


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


  55. 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. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2005. PMID: 16418779


  56. 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. The Journal of experimental medicine 2005. PMID: 16203866


  57. 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. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2004. PMID: 15619670


  58. 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. Proceedings of the National Academy of Sciences of the United States of America 2004. PMID: 15073337


  59. 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. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2003. PMID: 14969392


  60. 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. Journal of immunology (Baltimore, Md. : 1950) 2003. PMID: 14662855