Research Departments & Organizations
My research interests have evolved from laboratory-based investigation (Proc Natl Acad Sci USA. 1997; 94:7566-7571) to clinical and translational research dedicated to improving the lives of patients with SLE (Arthritis & Rheumatology. 2015 Jul;67(7):1848-57). The immunological mechanisms involved with lupus are complex, heterogeneous, and involve environmental triggers that are not yet clear. Lupus is an autoimmune disease that especially impacts women of childbearing age, so the burden of lifelong illness is great. I devote my research time to evaluating new therapeutics in SLE and identifying new signals for SLE disease activity, including analysis of activation signals in T-follicular helper cells.
Extensive Research Description
My interest in science, immunology, and rheumatology has been long-standing. This initially became manifest during my college career when I engaged in basic science research exploring the role of heat-shock response in archaea bacteria responsible for bio-remediation of sludge wastewater. That experience at the Wadsworth Center in Albany New York taught me basic laboratory principles, DNA extraction, northern (RNA) blood analysis, ELISA, immunohistochemistry, bacterial cell culture, glassware care, critical analysis of results, and scientific writing. Following that experience, I worked on masking red cell antigens in search of a blood substitute, and gained experience with laboratory animal use, biochemistry, and hematology. My interest in immunology deepened during my residency when I focused on elucidating T-cell differentiation and tolerance as caused by dendritic-cell interactions by specific serum proteins in the laboratories of Drs. Berhane Ghebrehiwet, Santiago-Schwartz and Richard Kalish, University Hospital and Medical Center, School of Medicine at Stony Brook, SUNY.
As a post-graduate fellow, I explored the cellular and molecular mechanisms of inflammation using a collagen-induced arthritis model and explored certain herbal effects on inflammation.
I made the leap to a clinical research career after fellowship and quickly focused on systemic lupus erythematosus, a disease under current investigation in Dr. Craft's laboratory at Yale. I launched my clinical research career after I joined Susan Manzi’s and Joe Ahearn's group at the University of Pittsburgh, internationally recognized lupus clinical researchers. They served as role models and mentors, from whom I acquired skills in the clinical assessment of lupus and the implementation of clinical research, both in the form of clinical trials and outcomes research. Under them, I was involved with several clinical trials, including vitamin D in SLE, combination therapies for lupus nephritis and lymphostat-B (belimumab) in treatment of SLE. Belimumab was the first new medication approved for SLE in over 50 years.I was site PI for several BLISS trials investigating belimumab for the treatment of SLE. This was the first drug approved by the FDA for the treatment of SLE in over 50 years. I was involved with the SABLE study, which follows SLE patients currently being treated with belimumab. I have been involved in research studying the effect of vitamin D in SLE. Collaboration with the Immune Tolerance Network led to me to being site PI for the abatacept in combination with cyclophosphamide for the treatment of lupus nephritis trial. I developed particular expertise in renal and neurologic SLE, pregnant rheumatic disease, and anti-phospholipid syndrome. I have used my skills to bring forth the clinical trial program at Yale for SLE, and have many active clinical trials underway.
Novel molecular therapeutic targets and new biomarkers of disease expression are necessary to advance clinical lupus care. Biomarker development for SLE was a major emphasis of my faculty mentors Susan Manzi and Joseph Ahearn at the University of Pittsburgh. At Yale, we have discovered a novel activation signal in human SLE, pSTAT4, a transcription factor necessary for the development of naïve CD4+ T follicular helper cells. To validate this finding in humans, I established the Yale Rheumatology bio-repository in 2016. Data from this cohort demonstrated a clear signal of STAT4 that correlates with SLE activity. As greater New Haven has a significant population of lupus, we have a rich source of subjects for clinical research. To accelerate clinical longitudinal research in lupus, I developed an on-line database inventory and disease activity capture system. This allows real time data capture while patients are enrolled into the longitudinal study during clinic visits.
Many of the academic centers that take part in lupus clinical trials are thought leaders in SLE. We have organized ourselves as LuCIN, allowing for multi-center investigations in SLE, with Yale being a keystone member, thereby accelerating the discovery of novel therapeutics for SLE.
|Diseases of the Kidney & Urinary Tract||Aurinia Renal Assessments 2: Aurinia Renal Response in Lupus With Voclosporin (AURORA2)|
|Immune System||JBT-101 in Systemic Lupus Erythematosus (SLE)|
|Diseases of the Musculoskeletal System||An Investigational Study to Evaluate BMS-986165 in Patients With Systemic Lupus Erythematosus|
|Immune System||Safety and Effectiveness of Belimumab in Systemic Lupus Erythematosus Registry (SABLE)|
|Immune System||A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE (RIFLE)|
|Immune System||A Study to Evaluate the Efficacy and Safety of CC-220 in Subjects With Active Systemic Lupus Erythematosus|
|Diseases of the Digestive System - Liver, Diseases of the Kidney & Urinary Tract, Immune System||Aurinia Renal Response in Active Lupus With Voclosporin (AURORA)|
Randomized, Double-Blind, Placebo-Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus Erythematosus.
Aranow C, Kamen DL, Dall'Era M, Massarotti EM, Mackay MC, Koumpouras F, Coca A, Chatham WW, Clowse ME, Criscione-Schreiber LG, Callahan S, Goldmuntz EA, Keyes-Elstein L, Oswald M, Gregersen PK, Diamond B. Randomized, Double-Blind, Placebo-Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus Erythematosus. Arthritis & Rheumatology (Hoboken, N.J.) 2015, 67:1848-57. 2015
Treatment of lupus nephritis with abatacept: the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study.
ACCESS Trial Group, Treatment of lupus nephritis with abatacept: the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study. Arthritis & Rheumatology. 2014 Nov;66(11):3096-104 2014
Effects of a novel tylophorine analog on collagen-induced arthritis through inhibition of the innate immune response.
You X, Pan M, Gao W, Shiah HS, Tao J, Zhang D, Koumpouras F, Wang S, Zhao H, Madri JA, Baker D, Cheng YC, Yin Z. Effects of a novel tylophorine analog on collagen-induced arthritis through inhibition of the innate immune response. Arthritis And Rheumatism 2006, 54:877-86. 2006
Chemical camouflage of antigenic determinants: stealth erythrocytes.
Scott MD, Murad KL, Koumpouras F, Talbot M, Eaton JW. Chemical camouflage of antigenic determinants: stealth erythrocytes. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94:7566-71. 1997
Rheumatic Manifestations of Systemic Disorders
Andreoli and Carpenter’s Cecil Essentials of Medicine, 8th Ed. 2008, pgs. 878-882 2008
Andreoli and Carpenter’s Cecil Essentials of Medicine, 8th Ed. 2008, pgs. 855-857 2008