Oklahoma Medical Research Foundation (OMRF)

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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.

Education
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

Other Activities
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

Memberships
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.

Recent Publications

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, Alarcon GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sanchez-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, 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 2012. [Abstract] EPub

* Kim K, Brown EE, Choi CB, Alarcón-Riquelme ME, on behalf of BIOLUPUS, Kelly JA, Glenn SB, Ojwang JO, Adler A, Lee HS, Boackle SA, Criswell LA, Alarcon GS, Edberg JC, Stevens AM, Jacob CO, Gilkeson GS, Kamen DL, Tsao BP, Anaya JM, Guthridge JM, Nath SK, Richardson B, Sawalha AH, Kang YM, Shim SC, Suh CH, Lee SK, Kim CS, Merrill JT, Petri M, Ramsey-Goldman R, Vila LM, Niewold TB, Martin J, Pons-Estel BA, on behalf of GENLES, Vyse TJ, Freedman BI, Moser KL, Gaffney PM, Williams A, Comeau M, Reveille JD, James JA, Scofield RH, Langefeld CD, Kaufman KM, Harley JB, Kang C, Kimberly RP, Bae SC. Variation in the ICAM1-ICAM4-ICAM5 locus is associated with systemic lupus erythematosus susceptibility in multiple ancestries. Ann Rheum Dis 2012. [Abstract] EPub

Selected Publications
Merrill JT, Burgos-Vargas R, Westhovens R, Chalmers A, D’Cruz D, Wallace DJ, Bae SC, Sigal L, Becker JC, Kelly S, Raghupathi K, Li T, Peng Y, Kinaszczuk M, Nash P. The efficacy and safety of abatacept in patients with non-life-threatening manifestations of systemic lupus erythematosus: results of a twelve-month, multicenter exploratory, phase IIb, randomized, double blind, placebo-controlled trial. Arthritis Rheum. 62:3077-3087, 2010. [Abstract]

Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC, Utset TO, Gordon C, Isenberg DA, Hsieh HJ, Zhang D, Brunetta PG. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: The randomized, double-blind, phase ii/iii systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 62:222-233, 2010. [Abstract]

Merrill JT, Buyon JP. Connective tissue diseases: what does the death of Riquent() hold for the future of SLE? Nat.Rev.Rheumatol. 5:306-307, 2009. [Abstract]

Hanly JG, Urowitz MB, Siannis F, Farewell V, Gordon C, Bae SC, Isenberg D, Dooley MA, Clarke A, Bernatsky S, Gladman D, Fortin PR, Manzi S, Steinsson K, Bruce IN, Ginzler E, Aranow C, Wallace DJ, Ramsey-Goldman R, van Vollenhoven R., Sturfelt G, Nived O, Sanchez-Guerrero J, Alarcón GS, Petri M, Khamashta M, Zoma A, Font J, Kalunian K, Douglas J, Qi Q, Thompson K, Merrill JT. Autoantibodies and neuropsychiatric events at the time of systemic lupus erythematosus diagnosis: Results from an international inception cohort study. Arthritis Rheum 58:843-853, 2008. [Abstract]

Merrill, JT Asherson, R. A. Catastrophic antiphospholipid syndrome. Nat Clin Pract Rheumatol 2(2), 81-89. 2006. [Abstract]

Ginzler EM, Dooley MA, Aranow C, Kim MY, Buyon J, Merrill JT, Petri M, Gilkeson GS, Wallace DJ, Weisman MH, Appel GB. Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. N Engl J Med 353:2219-2228, 2005. [Abstract]

Joan T. Merrill, M.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