Joan T. Merrill, M.D.
Member and Program Chair
Clinical Pharmacology Research Program
Professor, Department of Medicine, University of Oklahoma Health Sciences Center
Adjunct Associate Professor, Department of Medicine, New York University Medical Center
Lupus is a chronic autoimmune disease that can cause unpredictable flares of inflammation affecting almost any organ in the body. Although this illness can be relatively mild in many people, in others it can become quite severe or even life threatening, causing serious damage to the kidneys, heart, brain or lungs.
In my lab, we view lupus as an imbalance of the immune system rather than the immune system as some kind of enemy to a lupus patient. It’s there to defend us, not to attack us, but somehow, in lupus, it has become overactive in its defense, leading to excessive inflammation and collateral damage to the body.
The medicines used for lupus now work to suppress the immune system. But they also have unacceptable side effects and can impair the ability of the immune system to keep a person healthy, leading to serious infections and other unwanted consequences.
Instead, we’re looking for treatments that restore the balance of the immune system, such as new “biologic” treatments that can drill down and target even the tiny, individual proteins of the immune system, restoring its proper balance.
At OMRF, we run the Oklahoma Lupus Cohort—a group of more than 400 people with lupus who donate blood samples and clinical information for laboratory studies, so we can help develop new targeted treatments. We also do treatment studies for lupus patients who choose to participate in the testing of new biological agents. Some of the studies are very exciting, because they link laboratory studies with treatment assessments. Because people donate blood samples before, during and after the treatment, scientists can monitor the effects of the new treatments and learn more about the way the immune system actually works. And, because lupus is such a complicated disease, these studies may help to figure out which patients should be getting each specific treatment and what the best approach to dosing is.
B.A., Vassar College, Poughkeepsie, NY, 1972
M.D., Cornell University Medical College, New York, NY, 1985
Honors and Awards
2000 Edmund Dubois Award, American College of Rheumatology
2006 Ira Goldstein Award and Lectureship, New York University Advance Course in Rheumatology
Medical Director, Lupus Foundation of America 2004-present
Medical and Scientific Committee, National Arthritis Foundation 2000-2003
Research Committee and Clinical Research Subcommittee, American College of Rheumatology, 2002-2004
Chair, APLS Abst Subcommittee, American College of Rheumatology Meeting 1999-2002
Planning Committee, American College of Rheumatology Meeting, 1999-2002
American College of Rheumatology Sponsored Programs Committee 2001-2004
Vice-Chair, Medical and Scientific Committee, N.Y. Chapter Arthritis Foundation, 2000-2001
American College of Rheumatology
New York Academy of Science
The Henry Kunkel Society (elected 1998)
Systemic Lupus International Collaborating Clinics (elected 1998)
Joined OMRF Scientific Staff in 2001.
Heart attacks and strokes occur when fats slowly accumulate in blood vessels, causing breakdown of blood flow to arteries of the heart and brain. It is increasingly apparent that disorders in the regulation of inflammatory processes play a role in this accumulating process. Lupus is a disease characterized by flares of inflammation in the blood vessels, and lupus patients are at increased risk for premature atherosclerosis. The hypothesis underlying our work is that some of the specific disordered immune events that occur in lupus can shed light on the more low-grade inflammatory events that lead to progressive atherosclerosis in a wider, aging population.
Our research involves the study of variables that affect immune function and blood vessel regulation. We have three projects that follow patients over time: a national registry of the antiphospholipid syndrome, the SLICC registry, which studies risk factors for premature atherosclerosis (we are one of 30 sites around the world participating in this collaborative study), and basic research linked to pharmaceutical-sponsored clinical trials of investigational drugs for lupus.
Our group also does basic research into the ways in which lupus immune proteins interfere with structures that help maintain a healthy bloodstream. This includes antiphospholipid antibodies (which interfere with the blood clotting system), antibodies to proteins that regulate cholesterol and antibodies to other blood vessel regulators such as platelets.
The Clinical Pharmacology team works with several international groups to distill the complexities of lupus down to manageable and testable targets for new immune-modulating treatments. These projects range from the testing of updated disease criteria and clinical outcome measures (working with the Systemic Lupus International Collaborating Clinics) to the validation of improved biologic tests for determining the safety and effectiveness of investigational drugs (working with the NIH-based SLE Biomarkers Working Group). We have also developed projects during 2005 which link pharmaceutical-sponsored drug trials in lupus to basic laboratory research studies, including new projects with Genentech and Otsuka Pharmaceuticals.
Merrill JT. Co-stimulatory molecules as targets for treatment of lupus. Clin Immunol 2013. [Abstract] EPub
* Ramos PS, Oates JC, Kamen DL, Williams AH, Gaffney PM, Kelly JA, Kaufman KM, Kimberly RP, Niewold TB, Jacob CO, Tsao BP, Alarcón GS, Brown EE, Edberg JC, Petri MA, Ramsey-Goldman R, Reveille JD, Vilá LM, James JA, Guthridge JM, Merrill JT, Boackle SA, Freedman BI, Scofield RH, Stevens AM, Vyse TJ, Criswell LA, Moser KL, Alarcón-Riquelme ME, Langefeld CD, Harley JB, Gilkeson GS. Variable Association of Reactive Intermediate Genes with Systemic Lupus Erythematosus in Populations with Different African Ancestry. J Rheumatol 2013. [Abstract] EPub
Coit P, Jeffries M, Altorok N, Dozmorov MG, Koelsch KA, Wren JD, Merrill JT, McCune WJ, Sawalha AH. Genome-wide DNA methylation study suggests epigenetic accessibility and transcriptional poising of interferon-regulated genes in naive CD4+ T cells from lupus patients. J Autoimmun 2013. [Abstract] EPub
Merrill JT, Wallace DJ, Petri M, Kirou KA, Yao Y, White WI, Robbie G, Levin R, Berney SM, Chindalore V, Olsen N, Richman L, Le C, Jallal B, White B, Lupus Interferon Skin Activity (LISA) Study Investigators. Safety profile and clinical activity of sifalimumab, a fully human anti-interferon alpha monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study. Ann Rheum Dis 70:1905-1913, 2011. [Abstract]
Ruperto N, Hanrahan L, Alarcón G, Belmont H, Brey R, Brunetta P, Buyon J, Costner M, Cronin M, Dooley M, Filocamo G, Fiorentino D, Fortin P, Franks A, Jr., Gilkeson G, Ginzler E, Gordon C, Grossman J, Hahn B, Isenberg D, Kalunian K, Petri M, Sammaritano L, Sánchez-Guerrero J, Sontheimer R, Strand V, Urowitz M, von Feldt J., Werth V, Merrill J. International consensus for a definition of disease flare in lupus. Lupus 20:453-462, 2011. [Abstract]
Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, Karpouzas GA, Merrill JT, Wallace DJ, Yazdany J, Ramsey-Goldman R, Singh K, Khalighi M, Choi SI, Gogia M, Kafaja S, Kamgar M, Lau C, Martin WJ, Parikh S, Peng J, Rastogi A, Chen W, Grossman JM. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken ) 64:797-808, 2012. [Abstract]
Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sánchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, Van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG, Jr., Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G, Jr., Magder LS. Derivation and validation of Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64:2677-2686, 2012. [Abstract]
Steinman L, Merrill JT, McInnes IB, Peakman M. Optimization of current and future therapy for autoimmune diseases. Nat Med 18:59-65, 2012. [Abstract]
Merrill JT, Ginzler EM, Wallace DJ, McKay JD, Lisse JR, Aranow C, Wellborne FR, Burnette M, Condemi J, Zhong ZJ, Pineda L, Klein J, Freimuth WW, on Behalf of the LBSL. Long-term safety profile of Belimumab plus standard therapy in patients with systemic lupus erythematosus. Arthritis Rheum 64:3364-3373, 2012. [Abstract]
Clinical Pharmacology Research Program, MS 22
Oklahoma Medical Research Foundation
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