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James, Judith A.

Judith A. James, M.D., Ph.D.

Judith A. James, M.D., Ph.D.

Member and Program Chair
Arthritis & Clinical Immunology Research Program

Lou C. Kerr Endowed Chair in Biomedical Research

Professor, Department of Medicine, University of Oklahoma Health Sciences Center

Adjunct Professor, Department of Pathology, University of Oklahoma Health Sciences Center

Over the past several years, our laboratory has been very interested in how a person’s immune system can “go awry” and produce autoimmune diseases, such as systemic lupus erythematosus, scleroderma, multiple sclerosis, rheumatoid arthritis, and others. Systemic lupus erythematosus (SLE) is often considered the “prototype” of autoimmune disease and is characterized by the presence of high concentrations of autoantibodies. Unfortunately, the role of these autoantibodies in the onset and progression of lupus is unknown.

Our laboratory is approaching understanding these autoantibodies from several different directions. First, we describe the initial targets of these aberrant self-antibodies by testing serially collected serum samples from patients. These results have led to the description of a new “peptide-induced” animal model of SLE. Currently we are using this induced animal model to decipher which genes are involved in this animal model, as well as to understand which cells of the immune system play a role in this disease process. One of these genes in involved in how subsets of cells in the immune system talk to one another. Ongoing research is focused on understanding how these interactions do not lead to the appropriate dampening of immune responses and these abnormal responses could be modified for lupus treatment. From these studies we have also found a very powerful association between being previously exposed to Epstein-Barr virus (EBV) and developing SLE. In addition, we have found that lupus patients mount a distinctly different immune response to EBV proteins compared to normal controls. We are currently working on various mechanisms of how this virus may play a role in SLE. Our research group is also focusing efforts to understand how autoantibodies are involved in major organ damage and the genetic predisposition to these responses. Finally, based upon our autoimmune disease experience, we have begun to apply parallel approaches to understand other autoimmune diseases (such as scleroderma, multiple sclerosis and rheumatoid arthritis), as well as normal immune responses to vaccinations, such as anthrax and influenza.

B.S., Oklahoma Baptist University (summa cum laude with honors), 1989
Ph.D., University of Oklahoma Health Sciences Center, 1993
M.D., University of Oklahoma Health Sciences Center, 1994

Honors and Awards
1988 Sir Alexander Fleming Scholar, OMRF
Outstanding Chemistry Student East Award, Oklahoma Baptist University
Outstanding Pre-Medical Student, Oklahoma Baptist University
1990 Travel Award Recipient, National Meeting American College of Rheumatology
1990 Outstanding Poster Presentation Alpha Omega Alpha Student Research Day
1991 Travel Award Recipient, National Meeting American College of Rheumatology
1992 Outstanding Medical Student Award American College of Rheumatology
1992 Travel Award Recipient, National Meeting American Federation for Clinical Research
1992 Outstanding Poster Presentation Alpha Omega Alpha Student Research Day
1993 Travel Award Recipient National Meeting American Federation for Clinical Research
1993 Outstanding Poster Presentation Alpha Omega Alpha Student Research Day
1994 Outstanding Student Award American College of Rheumatology
1994 Alpha Omega Alpha, Medical Honor Society
1996 The Merrick Award for Outstanding Research, OMRF
1996 Outstanding Presentation Oklahoma State Internal Medicine and Oklahoma College of Physicians Meeting, Stillwater, OK
1997 Outstanding Presentation, Intern and Residents Day, University of Oklahoma Health Sciences Center
1996 Invited Lecture – “Lupus: A Disease Mystery”, OMRF 50th Anniversary
1998 Outstanding Oral and Poster Presentations, Intern and Residents Day, University of Oklahoma Health Sciences Center
2000 Merck Young Investigator Award
2000 Presidential Early Career Award for Scientists and Engineers
2001 Federation of Clinical Immunology Societies Junior Investigator Travel Award
2001 American Association of Immunologists Junior Faculty Travel Award
2001 Aesculapian Outstanding Medical Student Teaching Award Finalist Oklahoma University Health Sciences Center
2002 Byliner Award – Health Association for Women in Communications, Oklahoma City Chapter
2002 Henry Kunkel Society Membership
2003 Election to American Society of Clinical Investigation
2004 Edward L. & Thelma Gaylord Prize for Scientific Achievement
2005 OU Health Sciences Center Regent’s Award for Superior Research and Creative Activity

Other Activities
Lupus Foundation of America National Medical Council (1999 to present)
American College of Rheumatology Abstract Selection Subcommittee Chair (2001 to present)
American College of Rheumatology Basic Science Symposium Chair (2002-2004)
National Institutes of Health National Institute Arthritis, Musculoskeletal and Skin Disease AMS Study Section (2002-2006)
National Institutes of Health National Institute Arthritis, Musculoskeletal and Skin Disease R03 New Investigator Study Section (March 2001 – present)
Abstract Subcommittee Selection Committee Humoral Aspects of Autoimmunity
American College of Rheumatology (June 2001)
Section Chairman (2002-2003)
National Arthritis Foundation Study Section – Cellular Immunology (2000 to present)
Lupus Foundation of America National Medical Council – Grant Reviewer (1999 to present)
Ad Hoc Reviewer: VA Grant Review (National) (1997 to present)
Ad Hoc Reviewer: Journal of Immunology, Arthritis & Rheumatism, Journal of clinical Investigation, Journal of Experimental Medicine, Genes and Immunity, Scandinavian Journal of Immunology (1996 to present)
Graduate Program in Biomedical Sciences Advisory Committee Oklahoma University Health Sciences Center (2000 to present)
Lupus Foundation of Oklahoma Advisory Council (2000 to present)
Oklahoma Lupus Association, Inc. Board of Directory (2000 to present)

American College of Rheumatology
American Association of Immunologists
Clinical Immunology Society
Oklahoma State Medical Association
Assigned Medical Science National Review Study Section, National Institute of Arthritis, Musculoskeletal and Skin Disease, National Institutes of Health (2002-2007)
American College of Rheumatology, National Abstract Selection Committee, Humoral Aspects of Autoimmunity, Chair (2001-2003)
Lupus Foundation of America, National Medical Council
American College of Rheumatology, National Meetings Committee (2003-present)

Joined OMRF Scientific Staff in 1994.

Autoimmune diseases are a devastating plague to modern society which reminds us that the etiology and pathogenesis of many serious disease processes remain poorly understood. Our research efforts focus on understanding the initiating and pathogenic factors in systemic autoimmune rheumatic diseases.

Systemic lupus erythematosus is an autoimmune disease which is characterized by the production of high levels of autoantibodies. Our work on the immunochemistry of lupus autoantigens provides the basis for our ongoing research efforts. These epitope mapping experiments led to our peptide induced model of lupus autoimmunity. Genetic analysis of responder and non-responder strains have shown linkage and association with CD72, a polymorphic B cell marker involved in negative regulation of B cells in mouse and man. Using CD72 congenic mice and a large collection of well-characterized human SLE patients, our research efforts now focus on further understanding the role of CD72 in murine models and human SLE.

In addition, our laboratory is interested in understanding the pathogenic mechanisms of SLE epitope spreading. Serial serum samples from the Department of Defense Serum Repository show that autoantibodies precede clinical lupus and ongoing work focuses on understanding what specific features of antibodies might change in patient sera at the time of clinical SLE onset. Identification of early humoral autoimmune responses could potentially lead to cross-reactive structures from environmental pathogens which could trigger autoimmunity in susceptible individuals. This approach led to our identification of Epstein-Barr nuclear antigen-1 as the heteroimmune response out of which select aspects of lupus autoimmunity arises. Ongoing research focuses on understanding how such a common infectious agent could be related to such an uncommon disease. We are applying the lessons from SLE to other autoimmune rheumatic diseases, such as scleroderma.

The unifying theme of our research efforts is to understand the etiology and pathogenic mechanisms of systemic autoimmune, rheumatic disease. We use antigenic structure to introduce us to the critical molecular elements of the autoimmune process. By applying this information to human disease states, we hope to develop better diagnostic approaches and therapeutic interventions, as well as to contribute to the understanding of basic immune function.

Recent Publications

* Thanou A, Chakravarty E, James JA, Merrill JT. Which outcome measures in SLE clinical trials best reflect medical judgment? Lupus Sci Med 1:e000005, 2014. [Abstract]

* Kottyan LC, Zoller EE, Bene J, Lu X, Kelly JA, Rupert AM, Lessard CJ, Vaughn SE, Marion M, Weirauch MT, Namjou B, Adler A, Rasmussen A, Glenn S, Montgomery CG, Hirschfield GM, Xie G, Coltescu C, Amos C, Li H, Ice JA, Nath SK, Mariette X, Simon Bowman for UK primary Sjogren's syndrome registry, Rischmueller M, Lester S, Brun JG, Goransson LG, Harboe E, Omdal R, Cunninghame-Graham DS, Vyse T, Miceli-Richard C, Brennan MT, Lessard JA, Wahren-Herlenius M, Kvarnstrom M, Illei GG, Witte T, Jonsson R, Eriksson P, Nordmark G, Wan-Fai Ng for UK primary Sjogren's syndrome registry, Anaya JM, Rhodus NL, Segal BM, Merrill JT, James JA, Guthridge JM, Scofield RH, Alarcon-Riquelme M, Bae SC, Boackle SA, Criswell LA, Gilkeson G, Kamen DL, Jacob CO, Kimberly R, Brown E, Edberg J, Alarcon GS, Reveille JD, Vila LM, Petri M, Ramsey-Goldman R, Freedman BI, Niewold T, Stevens AM, Tsao BP, Ying J, Mayes MD, Gorlova OY, Wakeland W, Radstake T, Martin E, Martin J, Siminovitch K, Moser Sivils KL, Gaffney PM, Langefeld CD, Harley JB, Kaufman KM. The IRF5-TNPO3 association with systemic lupus erythematosus (SLE) has two components that other autoimmune disorders variably share. Hum Mol Genet 2014. [Abstract] EPub

Maier-Moore JS, Koelsch KA, Smith K, Lessard CJ, Radfar L, Lewis D, Kurien BT, Wolska N, Deshmukh U, Rasmussen A, Sivils KL, James JA, Farris AD, Scofield RH. Antibody-secreting cell specificity in labial salivary glands reflects clinical presentation and serology in Sjogren's syndrome patients. Arthritis Rheumatol 2014. [Abstract] EPub

Selected Publications

Smith K, Muther JJ, Duke AL, McKee E, Zheng NY, Wilson PC, James JA. Fully human monoclonal antibodies from antibody secreting cells after vaccination with Pneumovax(R)23 are serotype specific and facilitate opsonophagocytosis. Immunobiology 218:745-754, 2013. [Abstract]

Bruner BF, Guthridge JM, Lu R, Vidal G, Kelly JA, Robertson JM, Kamen DL, Gilkeson GS, Neas BR, Reichlin M, Scofield RH, Harley JB, James JA. Comparison of autoantibody specificities between traditional and bead-based assays in a large, diverse collection of patients with systemic lupus erythematosus and family members. Arthritis Rheum 64:3677-3686, 2012. [Abstract]

Gaddy JR, Vista ES, Robertson JM, Dedeke AB, Roberts VC, Klein WS, Levin JH, Mota FH, Cooper TM, Grim GA, Khan S, James JA. Rheumatic disease among Oklahoma tribal populations: a cross-sectional study. J Rheumatol 39:1934-1941, 2012. [Abstract]

Smith K, Crowe SR, Garman L, Guthridge C, Muther JJ, McKee E, Farris AD, Guthridge JM, Wilson PC, James JA. Human monoclonal antibodies generated following vaccination with AVA provide neutralization by blocking furin cleavage but not by preventing oligomerization. Vaccine 30:4276-4283, 2012. [Abstract]

Crowe SR, Merrill JT, Vista ES, Dedeke AB, Thompson DM, Stewart S, Guthridge JM, Niewold TB, Franek BS, Air GM, Thompson LF, James JA. Influenza vaccination responses in human systemic lupus erythematosus: impact of clinical and demographic features. Arthritis Rheum 63:2396-2406, 2011. [Abstract]

Ritterhouse LL, Crowe SR, Niewold TB, Kamen DL, Macwana SR, Roberts VC, Dedeke AB, Harley JB, Scofield RH, Guthridge JM, James JA. Vitamin D deficiency is associated with an increased autoimmune response in healthy individuals and in patients with systemic lupus erythematosus. Ann Rheum Dis 70:1569-1574, 2011. [Abstract]

View all publications in PubMed

Arthritis & Clinical Immunology Research Program, MS 53
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104

Phone: (405) 271-4987
Fax: (405) 271-7063

Joel Guthridge, Ph.D.
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