Patients with certain autoimmune diseases like lupus and Sjögren’s syndrome make abnormal immune responses to healthy tissue, in particular to components of the cell nucleus, where genetic information is stored. Most of these lupus “autoantigens” are also either DNA- or RNA-binding proteins. Studies in my laboratory have focused primarily on learning how the immune system normally learns not to respond to these types of nuclear components and, conversely, why these mechanisms don’t work in lupus. Our major approach has been to create and study genetically engineered mice that have very large numbers of immune T or B cells that can specifically bind to one particular RNA-binding lupus autoantigen called “La” that was discovered by our own Dr. Morris Reichlin. Because a normal mouse or person has as few as one in a million such cells —too few to study, these special mice, along with mice that have been engineered to express the human La antigen, are allowing us to find out for the first time how the immune system normally deals with these particular types of autoreactive immune cells. In the near future, we will have the capacity to study these questions in mice that have autoimmune pre-disposing genes in their genetic backgrounds that will allow us to find out exactly why and how certain genes promote autoimmunity.
More recently, our lab has partnered with Dr. Judith James to develop novel approaches to anthrax vaccination. Dr. James and her team are currently identifying short region (peptides) of the anthrax toxin proteins that are specifically bound by antibodies. The development of antibodies that can neutralize, or inhibit, the activity of anthrax toxins is the goal of vaccination; unfortunately, not all antibodies have this property. Our group will use the information obtained by Dr. James to determine which of the toxin component peptides can induce neutralizing antibodies. We will then create novel vaccine candidates by coupling the desirable peptides to a recombinant form of protective antigen, which will be initially tested in mice. It is our hope that these studies will lead to a safer and more effective anthrax vaccine.
The primary focus of our laboratory is to understand tolerance and autoimmunity to ubiquitous nuclear antigens that are targeted in systemic autoimmune diseases such as systemic lupus erythematosus and Sjögren’s syndrome. Using a human La (SS-B) transgenic mouse model and novel T cell receptor and B cell receptor transgenic models, we are delineating mechanisms of T and B cell tolerance to this ubiquitous, RNA-binding nuclear antigen.
A second major effort in our laboratory is to use animal models to decipher details of the neutralizing antibody response to major antigenic targets of Bacillus anthracis and then to use this information to improve current vaccine strategies to this bioterror threat.
B.S., Oklahoma Christian University of Science and Arts (summa cum laude), 1990
M.S., University of Oklahoma Health Sciences Center, 1993
Ph.D., Immunology, University of Oklahoma Health Sciences Center, 1995
Postdoctoral Studies, University of Melbourne, Melbourne, Australia, 1998
Honors and Awards
Rheumatology Research Foundation Innovative Grant Award, 2017-2019
American Association of Immunologists Travel Award to the 26th International Congress of Immunology in Melbourne, Australia, 2016
Oklahoma Christian University Biological Sciences Distinguished Alumnus Award, 2015
Henry Kunkel Society, Invited Member, Inducted April 21, 2010
OMRF Merrick Young Investigator Award, November 21, 2002
NIH K02 Independent Scientist Award, 2002-2007
American Association of Immunologists Travel Award to the 11th International Congress of Immunology in Stockholm, Sweden, 2001
OMRF Foundation Fellow, 2000
National Arthritis Foundation Postdoctoral Fellow, Jan 1997-Dec 1999
Plenary session presentation (abstract ranked #2) at American College of Rheumatology National Meeting, Orlando, Florida, 1996
NIH Training Grant Fellow, 1996
Grant reviews: Reviewer and Co-Chair, 2016/05 ZRG1 MOSS-K (57) SEP “Immune System Plasticity in the Pathogenesis and Treatment (2016); Standing Member, Oral Dental and Craniofacial Sciences Study Section (2015-2019); Ad hoc reviewer for NIH standing study sections and special emphasis panels on 9 occasions between 2001-2014; VA Merit Grant Reviewer for Department of Veteran’s Affairs (1999)
Journal reviews (since 2000 in alphabetical order): Annals of Rheumatic Diseases, Heliyon, Antimicrobial Agents and Chemotherapy, Arthritis and Rheumatism/Arthritis and Rheumatology, Autoimmunity, BMC Infectious Diseases, Cell Research, Clinical and Experimental Immunology, Clinical Ophthalmology, European Journal of Pharmacology, Immunology and Cell Biology, International Immunology, International Journal of Rheumatic Diseases, Journal of Immunology, Journal of Infection, Journal of Leukocyte Biology, Journal of Molecular Recognition, Medical Sciences, Molecular Immunology, Molecular Therapy-Methods & Clinical Development, Nature Immunology, PLoS One, Scandinavian Journal of Immunology, Scandinavian Journal of Rheumatology, Tissue Antigens, Vaccine
Session Chair, “Autoimmunity 3”, International Congress of Immunology, Melbourne Australia (2016); Co-chair, Concurrent Session “Sjögren’s Syndrome I: Basic Insights”, American College of Rheumatology Annual Meeting, (2015); Abstract Selection Committee, Sjögren’s syndrome category, American College of Rheumatology Annual Meeting (2015); Chair, Block Symposium “Genetic Susceptibility to Autoimmune Disease”, American Association of Immunologists National Meeting (2013); Co-chair, Sjögren’s Syndrome Study Group, American College of Rheumatology Annual National Meeting (2008), Co-chair, Concurrent Session “Roles for Apoptosis in Systemic Rheumatic Disease”, American College of Rheumatology Annual National Meeting (2002)
Lecturer: Advanced Immunology Course, Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center (OUHSC); Graduate Program in the Biological Sciences (GPiBs) 2nd year curriculum, OUHSC; Pathobiology Course, Department of Pathology, OUHSC
Mentoring of students: PhD Candidates, GPiBs rotating graduate students, Undergraduate Honors Thesis Students, OMRF Fleming Scholars Summer Research Program
OUHSC PhD Thesis Committees (Chair and Member, 2005-present)OUHSC Graduate Program in Biological Sciences Student Interviews (2013-present)OMRF Graduate Education Committee (2003-present)Coordination of Arthritis and Clinical Immunology Dept. seminars (2002-present)OMRF Institutional Animal Care and Use Committee (2003-2015)
American Association of Immunologists, 1999 to present
American College of Rheumatology, 2000 to present
American Society of Microbiology, 2008 to present
Henry Kunkel Society, 2010 to present
Joined OMRF Scientific Staff in 1999
Li H, Reksten TR, Ice JA, Kelly JA, Adrianto I, Rasmussen A, Wang S, He B, Grundahl KM, Glenn SB, Miceli-Richard C, Bowman S, Lester S, Eriksson P, Eloranta ML, Brun JG, Gøransson LG, Harboe E, Guthridge JM, Kaufman KM, Kvarnström M, Cunninghame Graham DS, Patel K, Adler AJ, Farris AD, Brennan MT, Chodosh J, Gopalakrishnan R, Weisman MH, Venuturupalli S, Wallace DJ, Hefner KS, Houston GD, Huang AJW, Hughes PJ, Lewis DM, Radfar L, Vista ES, Edgar CE, Rohrer MD, Stone DU, Vyse TJ, Harley JB, Gaffney PM, James JA, Turner S, Alevizos I, Anaya JM, Rhodus NL, Segal BM, Montgomery CG, Scofield RH, Kovats S, Mariette X, Rönnblom L, Witte T, Rischmueller M, Wahren-Herlenius M, Omdal R, Jonsson R, Ng WF; for UK Primary Sjögren's Syndrome Registry, Nordmark G, Lessard CJ, Sivils KL. Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons. PLoS Genet. 2017 Jun 22;13(6):e1006820. [Epub ahead of print] PMID: 28640813
Dumas EK, Garman L, Cuthbertson H, Charlton S, Hallis B, Engler RJM, Choudhari S, Picking WD, James JA, Farris AD. Lethal factor antibodies contribute to lethal toxin neutralization in recipients of anthrax vaccine precipitated. Vaccine. 2017 Jun 8;35(26):3416-3422. Epub 2017 May 11. [Abstract]
Garman L, Smith K, Muns EE, Velte CA, Spooner CE, Munroe ME, Farris AD, Nelson MR, Engler RJ, James JA. Unique Inflammatory Mediators and Specific IgE Levels Distinguish Local from Systemic Reactions After AVA Vaccination. Clin Vaccine Immunol. 2016 Jun 8. pii: CVI.00092-16.[Abstract] [Epub ahead of print]
Joachims ML, Leehan KM, Lawrence C, Pelikan RC, Moore JS, Pan Z, Rasmussen A, Radfar L, Lewis DM, Grundahl KM, Kelly JA, Wiley GB, Shugay M, Chudakov DM, Lessard CJ, Stone DU, Scofield RH, Montgomery CG, Sivils KL, Thompson LF, Farris AD. Single-cell analysis of glandular T cell receptors in Sjögren's syndrome. JCI Insight. 2016 Jun 2;1(8). pii: e85609. [Abstract]
Yaciuk JC, Pan Y, Schwarz K, Pan ZJ, Maier-Moore JS, Kosanke SD, Lawrence C, Farris AD. Defective selection of thymic regulatory T cells accompanies autoimmunity and pulmonary infiltrates in Tcra-deficient mice double transgenic for human La/Sjogren's syndrome-B and human La-specific TCR. J Immunol 2015. [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 66:3445-3456, 2014. [Abstract]
Garman L, Smith K, Farris AD, Nelson MR, Engler RJ, James JA. Protective antigen-specific memory B cells persist years after anthrax vaccination and correlate with humoral immunity. Toxins (Basel) 6:2424-2431, 2014. [Abstract]
Altorok N, Coit P, Hughes T, Koelsch KA, Stone DU, Rasmussen A, Radfar L, Scofield RH, Sivils KL, Farris AD, Sawalha AH. Genome-wide DNA methylation patterns in naive CD4 T cells from patients with primary Sjogren's syndrome. Arthritis Rheum 66:731-739, 2014. [Abstract]
Rasmussen A, Ice JA, Li H, Grundahl K, Kelly JA, Radfar L, Stone DU, Hefner KS, Anaya JM, Rohrer M, Gopalakrishnan R, Houston GD, Lewis DM, Chodosh J, Harley JB, Hughes P, Maier-Moore JS, Montgomery CG, Rhodus NL, Farris AD, Segal BM, Jonsson R, Lessard CJ, Scofield RH, Sivils KL. Comparison of the American-European Consensus Group Sjogren's syndrome classification criteria to newly proposed American College of Rheumatology criteria in a large, carefully characterised SICCA cohort. Ann Rheum Dis 73:31-38, 2014. [Abstract]
Arthritis & Clinical Immunology Research Program, MS 24
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-7389
Fax: (405) 271-4110
Zijian Pan, M.D.
Associate Staff Scientist
Michelle Joachims, Ph.D.
Associate Staff Scientist
Kerry Leehan, Ph.D.
Research Trainee (Polish Student Exchange Program)
Administrative Assistant III