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.
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. We have also developed projects which link pharmaceutical-sponsored drug trials in lupus to basic laboratory research studies. We have completed a recent study called Biomarkers of Lupus Disease (BOLD) which demonstrates the complexities of performing clinical trials with multiple background treatments being used and characterizes the immune interference of each of the most commonly used background treatments in these trials. We are currently studying dipyridamole and abatacept in trials of lupus that are capitalizing on information we learned from the BOLD study, trying to simplify background treatments and avoid the “noise” that interferes with figuring out how treatments work.
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
Chief Advisor for Clinical Development, Lupus Foundation of America 2016 - present
Medical Director, Lupus Foundation of America 2004-2016
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.
Langefeld CD, Ainsworth HC, Cunninghame Graham DS, ...Guthridge JM, Huggins JL, James JA, ... Merrill JT, Miranda P, Moctezuma JF, Nath SK, ... Sivils KL, ... Alarcón-Riquelme ME, ..., Gaffney PM, Vyse TJ. Transancestral mapping and genetic load in systemic lupus erythematosus. Nat Commun. 2017 Jul 17;8:16021. PMCID: PMC5520018
Kaplowitz ET, Ferguson S, Guerra M, Laskin CA, Buyon JP, Petri M, Lockshin MD, Sammaritano LR, Branch DW, Merrill JT, Katz P, Salmon JE. Socioeconomic Status Contributes to Racial/Ethnic Disparities in Adverse Pregnancy Outcomes among Women with Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2017 May 8. PMID:28480528
Kim M, Merrill J, Kalunian K, Hahn B, Roach A, Izmirly P; Lupus Foundation of America Collective Data Analysis Initiative Group.. Brief Report: Longitudinal Patterns of Response to Standard of Care Therapy for Systemic Lupus Erythematosus: Implications for Clinical Trial Design. Arthritis Rheumatol. 2017 Apr;69(4):785-90. PMID: 27992696
Gerosa M, Poletti B, Pregnolato F, Castellino G, Lafronza A, Silani V, Riboldi P, Meroni PL, Merrill JT. Antiglutamate Receptor Antibodies and Cognitive Impairment in Primary Antiphospholipid Syndrome and Systemic Lupus Erythematosus. Front Immunol. 2016 Feb 1;7:5. eCollection 2016. Review. PMCID:PMC4740786
Renauer P, Coit P, Jeffries MA, Merrill JT, McCune WJ, Maksimowicz-McKinnon K, Sawalha AH. DNA methylation patterns in naive CD4+ T cells identify epigenetic susceptibility loci for malar rash and discoid rash in systemic lupus erythematosus. Lupus Sci Med 2:e000101, 2015. PMCID:PMC4577980
* Zhao J, Wu H, Langefeld CD, ...James JA, Merrill JT, et al. Genetic associations of leptin-related polymorphisms with systemic lupus erythematosus. Clin Immunol. 2015. 2015 Dec;161(2):157-62. PMCID:PMC4658308
Furie R, Nicholls K, Cheng TT, Houssiau F, Burgos-Vargas R, Chen SL, Hillson JL, Meadows-Shropshire S, Kinaszczuk M, Merrill JT. Efficacy and safety of abatacept in lupus nephritis: a twelve-month, randomized, double-blind study. Arthritis Rheumatol. 2014 Feb;66(2):379-89. PMID:24504810
Stohl W, Merrill JT, McKay JD, Lisse JR, Zhong ZJ, Freimuth WW, Genovese MC. Efficacy and Safety of Belimumab in Patients with Rheumatoid Arthritis: A Phase II, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study. J Rheumatol. 2013 May;40(5):579-89. PMID:23547209
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. 2011 Nov;70(11):1905-13. PMID:21798883
Clinical Pharmacology Research Program, MS 22
Oklahoma Medical Research Foundation
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Oklahoma City, OK 73104
Phone: (405) 271-7805
Fax: (405) 271-3980
Clinical Trials Project Administrator
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