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
My lab seeks to increase the understanding of basic disease processes using immunologic approaches. By uncovering the cellular and molecular basis of disease, we can take rational approaches to development of effective therapies. In the rheumatic disease Sjögren’s syndrome (SS), we are applying new molecular tools to an old problem. Sjögren’s syndrome is a systemic rheumatic disease that selectively targets the moisture-producing salivary and lacrimal glands. Patients with Sjögren’s disease often have painful dry mouth and eyes, severe dental caries, fatigue, and arthritis. Why the salivary and lacrimal glands are involved in the disease process is a long-standing mystery. We are using single-cell molecular approaches to discover the substances and immune mechanisms that are causing the abnormal immune reactions occurring in salivary gland tissue from patients with SS.
Research
Sjögren’s syndrome (SS) is a systemic rheumatic disease that selectively targets the moisture-producing salivary and lacrimal glands. Patients with SS often have painful dry mouth and eyes, severe dental caries, fatigue, and arthritis. Why the salivary and lacrimal glands are involved in the disease process is a long-standing mystery. Our group is seeking to discover the substances and immune mechanisms that are causing the abnormal immune reactions occurring in salivary gland tissue from patients with SS. The approach we are using is to study gene expression of single immune cells isolated from salivary gland biopsy tissue from people who have SS. We are using lymphocyte receptors from the affected biopsy tissues to discover the substances, or antigens, causing their activation. So far, our work has identified a link between increased T helper cell clonal expansion, reduced salivary flow, and increased salivary gland damage.
Bacillus anthracis is a common organism occurring in the soil that can cause disease in farm animals. Unfortunately, spores from this organism, if inhaled into the lungs, can cause fatal disease in humans. While vaccination and antibiotics are effective for preventing serious human disease, better therapeutic approaches are needed to improve the survival rates if people become sick through inhalational exposure. Our group has discovered that this bacterium can inhibit one of the most important functions of macrophages: disposal of dead cells. Chronic impairment of this process is well known for leading to autoimmune responses in autoimmune diseases like lupus and SS. We think that impairment of this process during blood bacterial infections may amplify inflammation, leading to or worsening a potentially fatal complication known as sepsis. We are currently identifying the molecular mechanisms that Bacillus anthracis uses to inhibit the disposal of dead cells and seeking ways to counteract these effects.
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
2018 Merrick Award for Outstanding Medical Research
2017 – 2019 Rheumatology Research Foundation Innovative Grant Award
2016 American Association of Immunologists Travel Award to the 26th International Congress of Immunology in Melbourne, Australia
2015 Oklahoma Christian University Biological Sciences Distinguished Alumnus Award
2010 Henry Kunkel Society, Invited Member, Inducted April 21
2002 OMRF Merrick Young Investigator Award, November 21
2002 – 2007 NIH K02 Independent Scientist Award
1997 – 1999 National Arthritis Foundation Postdoctoral Fellow
Professional Activities
Grant reviews: Standing Member, Oral Dental and Craniofacial Sciences Study Section (2015-2019); Reviewer, 2017/06 ZRG1 MOSS K(57) SEP (2017); Reviewer and Co-Chair, 2016/05 ZRG1 MOSS-K (57) SEP (2016); 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, Basic & Clinical Pharmacology & Toxicology, BMC Infectious Diseases, Cell Research, Clinical and Experimental Immunology, Clinical Ophthalmology, Clinical Rheumatology, European Journal of Pharmacology, Heliyon, Histochemistry and Cell Biology, Immunology and Cell Biology, International Immunology, International Journal of Rheumatic Diseases, JCI Insight, Journal of Immunology, Journal of Infection, Journal of Leukocyte Biology, Journal of Molecular Recognition, Medical Microbiology & Immunology, Medical Sciences, Molecular Immunology, Molecular Therapy-Methods & Clinical Development, Nature Immunology, Nature Medicine, 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
Dumas EK, Demiraslan H, Ingram RJ, Sparks RM, Muns E, Zamora A, Larabee J, Garman L, Ballard JD, Boons GJ, James JA, Kayabas U, Doganay M, Farris AD. Toxin-neutralizing antibodies elicited by naturally acquired cutaneous anthrax are elevated following severe disease and appear to target conformational epitopes. PLoS One 15:e0230782, 2020 April, PMID: 32294093, PMCID: PMC7159215
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
Selected Publications
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. 2015 Feb 15;194(4):1514-22. 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. 2014 Dec;66(12):3445-56. PMID: 25199908 PMCID: PMC4245382
Maier-Moore JS*, Horton CG*, Mathews SA, Confer AW, Lawrence C, Pan Z, Coggeshall KM, Farris AD. Interleukin-6 Deficiency Corrects Nephritis, Lymphocyte Abnormalities and Secondary Sjögren's Features in Lupus-Prone Sle1.Yaa Mice. Arthritis Rheum. 2014 Sep;66(9):2521-31. PMID: 24891301 PMCID: PMC4146640
Pan ZJ, Maier S, Schwarz K, Azbill J, Akira S, Uematsu S, Farris AD. Toll-like receptor 7 (TLR7) modulates anti-nucleosomal autoantibody isotype and renal complement deposition in mice exposed to syngeneic late apoptotic cells. Ann Rheum Dis. 2010 Jun;69(6):1195-9. PMID: 19674980 PMCID: PMC2936817
Dudek NL, Maier S, Chen ZJ, Mudd PA, Mannering SI, Jackson DC, Zeng W, Keech CL, Hamlin K, Pan ZJ, Davis-Schwarz K, Workman-Azbill J, Bachmann M, McCluskey J, Farris AD. T cell epitopes of the La/SSB autoantigen in humanized transgenic mice expressing the HLA class II haplotype DRB1*0301/DQB1*0201. Arthritis Rheum. 2007 Oct;56(10):3387-98. PubMed PMID: 17907193. (**Selected for Editorial: Hoffman RW. T cells and the loss of immunologic tolerance in Sjogren's syndrome and systemic lupus erythematosus. Arthritis Rheum. 2007 Oct;56(10):3180-2.) PMID: 17907193
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
Sherri Longobardi
Senior Research Assistant
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 […]