Mary Beth Humphrey, MD, PhD - OU Medicine

Mary Beth Humphrey, MD, PhD
Associate Professor, Department of Medicine, Rheumatology and Immunology
SECTION: Rheumatology
CERTIFICATIONS: Rheumatology
Internal Medicine
ADDRESS: 975 N.E. 10 th St, BRC209
Oklahoma City, OK 73104
OFFICE PHONE: 405-271-8001x35290
FAX: 405-271-3229
E-MAIL: e-Mail Dr. Humphrey
Dr. Humphrey is a physician scientist at OUHSC since her relocation from the University of California at San Francisco in 2006.
She holds the James R. McEldowney Endowed Chair in Immunology and serves on a number of national committees, including
the National Institute of Dental and Craniofacial Research Special Grants Review Committee, the American Society of Bone and
Mineral Research Women’s Committee, and the Scientific Advisory Committee for the International Bone and Mineral Society
Sun Valley Musculoskeletal Workshop. Locally, she serves on the OCAST Health Research Committee. She has won numerous
research awards including the Ephraim Engleman Award for Excellence in the Field of Arthritis and the Presidential Early Career
Award in Science and Engineering (PECASE) awarded by President Bush in 2008. In addition to her active research program, Dr.
Humphrey participates in clinical duties in the Rheumatology Fellowship Program and the Department of Medicine.
EDUCATION:
August 1988- June 30, 1997 MD, PhD, Baylor College of Medicine, Houston, Texas
July 1, 1997 – June 30, 1998 Medicine Internship, University of California, San Francisco, California
July 1, 1998 – June 30, 2000 Medicine Residency, University of California, San Francisco, California
July 1, 2000 – June 30, 2001 Chief Medical Resident, San Francisco General Hospital, UCSF, San Francisco
July 1, 2001 – June 30, 2004 Fellow, Division of Rheumatology, Department of Medicine, University of
California, San Francisco, California
CLINICAL INTERESTS:
General Rheumatology
RESEARCH INTERESTS:
Dr. Humphrey’s research program centers on two main themes: Osteoimmunology and Systemic Lupus Erythematosus (SLE).
Osteoimmunology is the study of bone, bone cells, and the immune system. Recent studies have highlighted the importance of
normal bone and bone cells to maintain hematopoietic stem cell niches. Immune cells including macrophages, dendritic cells,
and T cells also actively participate in abnormal bone responses as seen in diseases such as rheumatoid arthritis. Dr. Humphrey
is focusing on the role of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters and their receptors in
controlling osteoclast differentiation and activation. . Her studies thus far have revealed unique requirements for the ITAMadapters
in osteoclast biology and in vivo bone remodeling. Additional studies are aimed at determining the role of ITAMadapters
in the negative regulation of Toll-like receptor (TLR) signaling.
The second main thrust of the Humphrey lab is aimed at determining the causal relationship between small nucleotide
polymorphism (SNPs) in the TNFAIP3 gene and their relationship to SLE. TNFAIP3 encodes an ubiquitin modifying protein, A20,
a critical negative regulator of cellular activation downstream of TLRs and Tumor necrosis factor family receptors, among
others. Studies are underway to identify functional consequences in immune cells expressing the risk allele of TNFAIP3. Results
of these studies will further our understanding of the mechanisms driving the development of SLE and may lead to new
therapeutic targets to control the disease.
RECENT PUBLICATIONS:
Humphrey, M.B.*, D.H. Chung*, M. C. Nakamura, D. G. Ginzinger, W. E. Seaman, M. R. Daws. CMRF-35-Like Molecule-1, a novel
mouse myeloid receptor, can inhibit osteoclast formation. Journal of Immunology. 2003, 171: 6541-6548. (* Co-first authors)

Humphrey, M.B., K. Ogasawara, W. Yao, S. C. Spusta, M. R. Daws, N. E. Lane, L. L. Lanier, M. C. Nakamura. The Signaling Adapter
Protein DAP12 Regulates Multinucleation During Osteoclast Development. Journal of Bone and Mineral Research. 2004,
19:224-234. Published on line December 16, 2003 doi 10.1359/JBMR0301234.
Humphrey, M. B.*, A. Mócsai*, J.A.G. Van Ziffle, Y. Hu, A. Burghardt, S. Spusta, S. Majumdar, L. L. Lanier, C. A. Lowell, M. C.
Through the Syk Tyrosine Kinase. Proceedings of the National Academy of Sciences. 2004, 101:6158-6163. (* Co-first authors)
Lane, N. E., W. Yao, M. C. Nakamura, M. B. Humphrey, D. Kimmel, X. Huang, d. Sheppard, P.F. Ross, and S. L. Teitelbaum. Mice
lacking Integrin
Journal of Bone and Mineral Research. 2005, 20:58-66. Published on line October 25, 2004 doi 10.1359/JBMR041017.
Humphrey, M.B., M. R. Daws, S. C. Spusta, E. C. Niemi, J. A. Torchia, L. L. Lanier, W. E. Seaman, and M. C. Nakamura. TREM2, a
DAP12-associated Receptor, Regulates Osteoclast Differentiation and Function. Journal of Bone and Mineral Research, 2006,
21:237-245. Published on line October 24, 2005 doi 10.1359/JBMR.051016.
Hamerman, J.A., J. R. Jarjoura, M.B. Humphrey, M.C. Nakamura, W.E. Seaman and L.L. Lanier. Cutting Edge: Inhibition of TLR
and FcR responses in macrophages by TREM-2 and DAP12. Journal of Immunology, 2006, 177(4):2051-5.
Wu, Y., J.A. Torchia, W. Yao, N.E. Lane, L.L. Lanier, M.C. Nakamura, and M.B. Humphrey. Bone Microenvironment Specific
Roles of ITAM Signaling In Bone Remodeling Induced by Acute Estrogen-deficiency. Public Library of Science ONE, 2007,
2(7):E586. doi:10371/journal.pone.0000586.
Charles, J.F., M.B. Humphrey, X. Zhao, E. Quarles, M.C. Nakamura, A. Aderem, W.E. Seaman, K.D. Smith. The innate immune
response to Salmonella by macrophages is dependent on TREM2-DAP12. Infection and Immunity, 2008, Apr 7 [Epub ahead of
print] PMID: 18391000
Bates, JS, CJ Lessard, JM Leon, T Nguyen, LJ Battiest, J Rodgers, KM Kaufman, JA James, GS Gilkeson, JA Kelly, MB Humphrey, JB
Harley, C Gray-McGuire, KL Moser1and PM Gaffney. Meta-analysis and imputation identifies a 109 kb risk haplotype spanning
TNFAIP3 associated with lupus nephritis and hematologic manifestations. Genes and Immunity, 2009, 10: 470-477.
Park-Min, K.H., J.D. Ji, T. Antoniv, A.C. Ried, R. B. Silver, M.B. Humphrey, M. Nakamura, and L.B. Ivashkiv. IL-10 suppresses
calcium-mediated costimulation of receptor activator NF-kB signaling during human osteoclast differentiation by inhibiting
TREM-2 Expression. Journal of Immunology, 2009, 183:2444-2455.
Peng, Q., Coggeshall, K.M., Torchia, J.A., and M.B. Humphrey. TREM2- and DAP12-Dependent Activation of PI3K Requires
DAP10 and is Inhibited by SHIP1. Science Signaling, May, 2010, (3) 122
Chang JL, Brauer DS, Johnson J, Chen CG, Akil O, Balooch G, Humphrey MB, Chin EN, Porter AE, Butcher K, Ritchie RO, Schneider
RA, Lalwani A, Derynck R, Marshall GW, Marshall SJ, Lustig L, Alliston T. Tissue-specific calibration of extracellular matrix
material properties by transforming growth factor-β and Runx2 in bone is required for hearing. EMBO Rep. Sept 2010 [Epub
ahead of print]PMID: 20847738
Adrianto, Wen, Templeton, Wiley, King, Lessard…Humphrey*, MB, Gray Montgomery*, C, and PM Gaffney* (* Co-directors of
the project) Association between functional tandem variants downstream of TNFAIP3 and systemic lupus erythematosus. In
press Nature Genetics