Mary Nakamura, MD


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.
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
  1. Proinflammatory cytokines and ARDS pulmonary edema fluid induce CD40 on human mesenchymal stromal cells-A potential mechanism for immune modulation.
  2. Lower PDL1/2 and AXL Expression on Lung Myeloid Cells Suggests Inflammatory Bias in Smoking and COPD.
  3. Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation.
  4. Age-related changes to macrophages are detrimental to fracture healing in mice.
  5. Female-Specific Role of Progranulin to Suppress Bone Formation.
  6. Osteoimmunology: entwined regulation of integrated systems.
  7. NF-?B/MAPK activation underlies ACVR1-mediated inflammation in human heterotopic ossification.
  8. Effects of Aging on Fracture Healing.
  9. A Comprehensive Review of Immunoreceptor Regulation of Osteoclasts.
  10. Brain trauma elicits non-canonical macrophage activation states.
  11. Triggering receptor expressed on myeloid cells 2 (TREM2) deficiency attenuates phagocytic activities of microglia and exacerbates ischemic damage in experimental stroke.
  12. CCR2 deficiency impairs macrophage infiltration and improves cognitive function after traumatic brain injury.
  13. Bone and the innate immune system.
  14. CIITA: a master regulator of adaptive immunity shows its innate side in the bone.
  15. Triggering Receptor Expressed on Myeloid Cells-2 Correlates to Hypothermic Neuroprotection in Ischemic Stroke.
  16. Traumatic brain injury induces macrophage subsets in the brain.
  17. Inflammatory arthritis increases mouse osteoclast precursors with myeloid suppressor function.
  18. PSTPIP2 deficiency in mice causes osteopenia and increased differentiation of multipotent myeloid precursors into osteoclasts.
  19. Expression of A20 by dendritic cells preserves immune homeostasis and prevents colitis and spondyloarthritis.
  20. Effects of inflammation on bone: an update.
  21. Assessment of bone remodelling in childhood-onset systemic lupus erythematosus.
  22. The loss of Cbl-phosphatidylinositol 3-kinase interaction perturbs RANKL-mediated signaling, inhibiting bone resorption and promoting osteoclast survival.
  23. Clinical diagnosis of segmental arterial mediolysis: differentiation from vasculitis and other mimics.
  24. Multiple roles for CCR2 during fracture healing.
  25. Binding and uptake of H-ferritin are mediated by human transferrin receptor-1.
  26. IL-10 suppresses calcium-mediated costimulation of receptor activator NF-kappa B signaling during human osteoclast differentiation by inhibiting TREM-2 expression.
  27. A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia.
  28. 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.
  29. The innate immune response to Salmonella enterica serovar Typhimurium by macrophages is dependent on TREM2-DAP12.
  30. Osteoclasts - the innate immune cells of the bone.
  31. Bone microenvironment specific roles of ITAM adapter signaling during bone remodeling induced by acute estrogen-deficiency.
  32. Cutting edge: inhibition of TLR and FcR responses in macrophages by triggering receptor expressed on myeloid cells (TREM)-2 and DAP12.
  33. Role of ITAM-containing adapter proteins and their receptors in the immune system and bone.
  34. TREM2, a DAP12-associated receptor, regulates osteoclast differentiation and function.
  35. TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis.
  36. Mice lacking the integrin beta5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state.
  37. The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase.
  38. The signaling adapter protein DAP12 regulates multinucleation during osteoclast development.
  39. CMRF-35-like molecule-1, a novel mouse myeloid receptor, can inhibit osteoclast formation.