Oklahoma Medical Research Foundation (OMRF)

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Our Lab

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.

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
Postdoc, University of Melbourne, Melbourne, Australia, 1998

Honors and Awards
1986-1990 Presidential Scholar, Oklahoma Christian University
1987 Outstanding Freshman Student in the Biological Sciences, Oklahoma Christian University
1987-1990 Alpha Chi National Honor Society
1990 Senior Science Award, Oklahoma Christian University
1992 American College of Rheumatology Student Travel Award
1993-1995 OUHSC Graduate Student Association High GPA Award
1993-1995 Oklahoma Medical Research Foundation Predoctoral Fellow
1995 OUHSC Graduate Student Association Grant Award
1995 Alpha Epsilon Lambda National Graduate and Professional Honor Society, Delta Chapter
1996 NIH Training Grant Fellow
1996 Plenary Session Presentation, American College of Rheumatology National Meeting, Orlando Florida
1997-1999 National Arthritis Foundation Postdoctoral Fellow
2000 OMRF Foundation Fellow
2001 American Association of Immunologists Travel Award to the 11th International Congress of Immunology, Stockholm, Sweden
2002 The Merrick Award for Outstanding Research

Other Activities
Invited lecturer: 2009 Workshop on the Immunology of Anthrax, Cardiff, Wales
Grant Reviewing: VA merit grants, NIH NIAMS Special Emphasis Panel, 2001-2002, NIH IRG Special Study Section, 2006
Journal reviewing: Arthritis and Rheumatism, International Immunology, Clinical and Experimental Immunology, Scandinavian Journal of Immunology, Tissue Antigens, European Journal of Pharmacology, Cell Research, Nature Immunology, Journal of Immunology
Meeting Session Chairing: ACR concurrent session co-chair, 2002; ACR Sjögren’s syndrome study group co-chair, 2008
Lecturer, Advanced Immunology Course, Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center
Lecturer, Graduate Program in the Biological Sciences (GPiBs) 2nd year curriculum, University of Oklahoma Health Sciences Center
Lecturer, Pathobiology Course, Department of Pathology, University of Oklahoma Health Sciences Center
Mentoring of students: PhD Candidates, GPiBs rotating graduate students, Undergraduate Honors Thesis Students, OMRF Fleming Scholars Summer Research Program and Presbyterian Health Foundation Summer Scholars Program for M.D. students
Institutional Committees:
OMRF Fleming Scholar Selection Committee, 2002
OMRF Annual Retreat Planning Committee, 2002 – 2005
OMRF Institutional Animal Care and Use Committee, 2002 – present
OMRF Graduate Education Committee, 2002 – present
OMRF Special Committee 2, 2002 – present
OUHSC Department of Microbiology and Immunology Qualifying Examinations Committee, 2002
Member, OMRF Research Forum Committee, 2005 – present

Memberships
American Association of Immunologists, 1999 to present
American College of Rheumatology, 2000 to present
American Society of Microbiology, 2008 to present

Joined OMRF Scientific Staff in 1999.

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.

Recent Publications

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 2012. [Abstract] EPub

Horton CG, Farris AD. Toll-like Receptors in Systemic Lupus Erythematosus: Potential Targets for Therapeutic Intervention. Curr Allergy Asthma Rep 12:1-7, 2012. [Abstract]

Dumas EK, Cox PM, Fullenwider CO, Nguyen M, Centola M, Frank MB, Dozmorov I, James JA, Farris AD. Anthrax lethal

Selected Publications
Charles E, Joshi S, Ash JD, Fox BA, Farris AD, Bzik DJ, Lang ML, Blader IJ. CD4 T-cell suppression by cells from Toxoplasma gondii-Infected retinas is mediated by surface protein PD-L1. Infect Immun 78:3484-3492, 2010. [Abstract]

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 69:1195-1199, 2010. [Abstract]

Nguyen ML, Terzyan S, Ballard JD, James JA, Farris AD. The Major neutralizing antibody responses to recombinant anthrax lethal factor and edema factors are directed to non-cross-reactive epitopes. Infect Immun 77:4714-4723, 2009. [Abstract]

Nguyen ML, Crowe SR, Kurella S, Teryzan S, Cao B, Ballard JD, James JA, Farris AD. Sequential B cell epitopes of Bacillus anthracis lethal factor bind lethal toxin-neutralizing antibodies. Infect Immun 77:162-169, 2009. [Abstract]

Maeda K, Malykhin A, Teague-Weber BN, Sun XH, Farris AD, Coggeshall KM. Interleukin 6 aborts lymphopoiesis and elevates production of myeloid cells in systemic lupus erythematosis-prone B6.Sle1.Yaa animals. Blood 113:4534-4540, 2009. [Abstract]

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 56:3387-3398, 2007. [Abstract]

A. Darise Farris, Ph.D.

Collaboration yields new ocular disease target

$2.4 million grant awarded to Oklahoma hearing loss project

OMRF scientists look at whether we can change genetic destiny

OMRF begins studies of celiac disease