A. Darise Farris, Ph.D.
Member
Arthritis & Clinical Immunology Research Program
Adjunct Associate Professor, Departments of Microbiology & Immunology and Pathology, University of Oklahoma Health Sciences Center
My 101
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.
Research
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.
Brief CV
Education
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
Professional Activities
Grant reviews:Reviewer, 2017/06 ZRG1 MOSS K(57) SEP (2017); Reviewer and Co-Chair, 2016/05 ZRG1 MOSS-K (57) SEP (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, Clinical Rheumatology, European Journal of Pharmacology, Heliyon, 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, Scientific Reports, Tissue Antigens, Vaccine
Society service:
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)
Educational Activities:
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, OMRF Fulbright Scholars Program
Institutional Committees:
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)
Memberships
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
Publications
Recent Publications
Pan Z, Dumas EK, Lawrence C, Pate L, Longobardi S, Wang X, James JA, Kovats S, Farris AD. Bacillus anthracis Edema Toxin Inhibits Efferocytosis in Human Macrophages and Alters Efferocytic Receptor Signaling. Int J Mol Sci 20, 2019 March, PMID: 30866434, PMCID: PMC6429438
Koelsch KA, Cavett J, Smith K, Moore JS, Lehoux SD, Jia N, Mather T, Quadri SMS, Rasmussen A, Kaufman CE, Lewis DM, Radfar L, Scordino TA, Lessard CJ, Kurien BT, Cummings RD, James JA, Sivils KL, Farris AD, Scofield RH. Evidence of Alternative Modes of B Cell Activation Involving Acquired Fab Regions of N-Glycosylation in Antibody-Secreting Cells Infiltrating the Labial Salivary Glands of Patients With Sjögren's Syndrome. Arthritis Rheumatol 70:1102-1113, 2018 July, PMID: 29457375, PMCID: PMC6019603
Leehan KM, Pezant NP, Rasmussen A, Grundahl K, Moore JS, Radfar L, Lewis DM, Stone DU, Lessard CJ, Rhodus NL, Segal BM, Scofield RH, Sivils KL, Montgomery C, Farris AD. Minor salivary gland fibrosis in Sjögren's syndrome is elevated, associated with focus score and not solely a consequence of aging. Clin Exp Rheumatol 36 Suppl 112:80-88, 2018 May, PMID: 29148407, PMCID: PMC5913007
Selected Publications
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. PMID: 28504191 PMCID: PMC5512426
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. PMID: 27280620 PMCID: PMC4979178
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. PMID: 27358913 PMCID: PMC4922426
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 Feb 15;194(4):1514-22, 2015. PMID: 25582858 PMCID: PMC4323622
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. PMID: 25199908 PMCID: PMC4245382
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. PMID: 25123559 PMCID: PMC4147590
Contact
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
E-mail: Darise-Farris@omrf.org
Lab Staff
Michelle Joachims, Ph.D.
Associate Staff Scientist
Zijian Pan, M.D.
Associate Staff Scientist
Christina Lawrence
Research Assistant
Charmaine Moya
Research Technician
Ananth "Adi" Jupudi
Graduate Student
Sherri Longobardi
Graduate Student
Josh Mytych
Graduate Student
Louise Williamson
Administrative Assistant III
News from the Farris lab
When a team of OMRF scientists set out to improve the anthrax vaccine, they started with a theory everybody thought would work: Break apart the toxins so they can’t enter cells. Problem solved. But things don’t always work as expected. In fact, the theory doesn’t work at all, according to a paper by OMRF’s Darise […]
A new study from OMRF has discovered that lurking in the bodies even of healthy people are numerous rogue immune cells, the cause of rheumatoid arthritis and a host of other diseases. The new findings could be key to developing new ways to prevent and treat autoimmune diseases, conditions like rheumatoid arthritis, lupus and type […]
Connor Fullenwider, a 2005 graduate of Muskogee High School, will spend his summer vacation as a Presidential Scholar at OMRF. Fullenwider, currently a sophomore at the United States Naval Academy in Annapolis, Md., will complete a research project focused on the study of anthrax under the guidance of Darise Farris, Ph.D., in OMRF’s Arthritis and […]
Nearing the mid-point of an historic five-year research project, the Oklahoma Medical Research Foundation announced today that it is making important strides toward developing more effective vaccines and treatments for the deadly infectious disease anthrax. In a study involving 120 military personnel, Judith James, M.D., Ph.D., Sherry Crowe, Ph.D., and Darise Farris, Ph.D., have identified […]
Oklahoma Medical Research Foundation scientist John Harley, M.D., Ph.D., has been named the inaugural recipient of a mentoring award from the nation’s leading rheumatology organization. Harley will be honored in Washington D.C. during the 70th Annual Scientific Meeting of the American College of Rheumatology (ACR) Research and Education Foundation. The new Excellence in Investigative Mentoring […]