Fotios Koumpouras, MD
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Research Summary
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. 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. This allows real time data capture while patients are enrolled into the longitudinal study during clinic visits.
We are a part of the Lupus Clinical Investigators Network (LuCIN) a division of the Lupus Research Alliance (LRA), and evaluate many new therapies for the treatment of lupus as part of a collaborative effort to accelerate the discovery of new therapies for systemic lupus.
Coauthors
Research Interests
Education, Graduate; Lupus Erythematosus, Systemic; Lupus Nephritis; Therapeutics; Biomarkers; Randomized Controlled Trials as Topic
Public Health Interests
Health Policy
Selected Publications
- Obexelimab in Systemic Lupus Erythematosus With Exploration of Response Based on Gene Pathway Co‐Expression Patterns: A Double‐Blind, Randomized, Placebo‐Controlled, Phase 2 TrialMerrill J, Guthridge J, Smith M, June J, Koumpouras F, Machua W, Askanase A, Khosroshahi A, Sheikh S, Rathi G, Burington B, Foster P, Matijevic M, Arora S, Wang X, Gao M, Wax S, James J, Zack D. Obexelimab in Systemic Lupus Erythematosus With Exploration of Response Based on Gene Pathway Co‐Expression Patterns: A Double‐Blind, Randomized, Placebo‐Controlled, Phase 2 Trial. Arthritis & Rheumatology 2023, 75: 2185-2194. PMID: 37459248, DOI: 10.1002/art.42652.
- Vascular-Targeted Therapy for Systemic Lupus Erythematosus–Associated VasculitisXu S, Patrignelli R, Ramachandran S, Koumpouras F, Desir D, Ko C, Gehlhausen J. Vascular-Targeted Therapy for Systemic Lupus Erythematosus–Associated Vasculitis. JAMA Dermatology 2023, 159: 460-462. PMID: 36884229, DOI: 10.1001/jamadermatol.2023.0077.
- Chapter 11 Interferons and cytokines in SLE pathogenesis and therapyKoumpouras F, Bucala R. Chapter 11 Interferons and cytokines in SLE pathogenesis and therapy. 2021, 169-180. DOI: 10.1016/b978-0-12-820583-9.00015-4.
- IL-7 receptor alpha defines heterogeneity and signature of human effector memory CD8+ T cells in high dimensional analysisShin MS, Kim D, Yim K, Park HJ, You S, Dong X, Koumpouras F, Shaw AC, Fan R, Krishnaswamy S, Kang I. IL-7 receptor alpha defines heterogeneity and signature of human effector memory CD8+ T cells in high dimensional analysis. Cellular Immunology 2020, 355: 104155. PMID: 32619811, PMCID: PMC7415611, DOI: 10.1016/j.cellimm.2020.104155.
- Stand Together and Deliver: Challenges and Opportunities for Rheumatology Education During the COVID‐19 PandemicKoumpouras F, Helfgott S. Stand Together and Deliver: Challenges and Opportunities for Rheumatology Education During the COVID‐19 Pandemic. Arthritis & Rheumatology 2020, 72: 1064-1066. PMID: 32270923, PMCID: PMC7262333, DOI: 10.1002/art.41278.
- Defining heterogeneity and biological signature in human effector memory CD8+ T cells expressing different levels of IL-7 receptor alpha by high-dimensional analysisShin M, Kim D, Park H, Dong X, Koumpouras F, Kang I. Defining heterogeneity and biological signature in human effector memory CD8+ T cells expressing different levels of IL-7 receptor alpha by high-dimensional analysis. The Journal Of Immunology 2020, 204: 154.19-154.19. DOI: 10.4049/jimmunol.204.supp.154.19.
- FRI0176 PHASE 2, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF A REVERSIBLE B CELL INHIBITOR, XMAB®5871, IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)Merrill J, June J, Koumpouras F, Machua W, Khan M, Askanase A, Khosroshahi A, Sheikh S, James J, Guthridge J, Rathi G, Burington B, Foster P, Zack D. FRI0176 PHASE 2, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF A REVERSIBLE B CELL INHIBITOR, XMAB®5871, IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE). 2019, 761.2-762. DOI: 10.1136/annrheumdis-2019-eular.4234.
- 98 Results of a phase 2, double-blind, randomized, placebo-controlled study of a reversible B cell inhibitor, XmAb®5871, in systemic lupus erythematosus (SLE)Merrill J, June J, Koumpouras F, Machua W, Khan M, Askanase A, Sheikh S, Khosroshahi A, Foster P, Zack D. 98 Results of a phase 2, double-blind, randomized, placebo-controlled study of a reversible B cell inhibitor, XmAb®5871, in systemic lupus erythematosus (SLE). 2019, a73-a74. DOI: 10.1136/lupus-2019-lsm.98.
- LB1601 Dermatomyositis-related panniculitis of the neckValladares H, Ramachandran S, Koumpouras F. LB1601 Dermatomyositis-related panniculitis of the neck. Journal Of Investigative Dermatology 2018, 138: b23. DOI: 10.1016/j.jid.2018.06.141.
- Randomized, Double‐Blind, Placebo‐Controlled Trial of the Effect of Vitamin D3 on the Interferon Signature in Patients With Systemic Lupus ErythematosusAranow 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 2015, 67: 1848-1857. PMID: 25777546, PMCID: PMC4732716, DOI: 10.1002/art.39108.
- 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
- 133 Hydroxychloroquine-Induced Lipidosis: Boon for Lupus Nephritis Becomes BaneJindal N, Koumpouras F, McHale T, Bastacky S, Liang K. 133 Hydroxychloroquine-Induced Lipidosis: Boon for Lupus Nephritis Becomes Bane. American Journal Of Kidney Diseases 2011, 57: b50. DOI: 10.1053/j.ajkd.2011.02.136.
- Chapter 85 Sjögren SyndromeKoumpouras F. Chapter 85 Sjögren Syndrome. 2010, 855-857. DOI: 10.1016/b978-1-4160-6109-0.00085-x.
- Chapter 90 Rheumatic Manifestations of Systemic DisordersKoumpouras F. Chapter 90 Rheumatic Manifestations of Systemic Disorders. 2010, 878-882. DOI: 10.1016/b978-1-4160-6109-0.00090-3.
- Lead Authors and ContributorsBenjamin I, Tariq S, Beland S, Benjamin I, Bull D, Hamdan M, Li D, Litwin S, Michaels A, Morshedzadeh J, Stehlik J, Whitehead K, Victor R, Vongpatanasin W, Rounds S, Aliotta J, Casserly B, Jankowich M, McCool F, Eagle K, Lau W, Harris R, Andreoli T, Basford A, Cavanaugh K, Dwyer J, Golper T, Krause M, Ikizler T, Lewis J, Luther J, Pirkle J, Portilla D, Safirstein R, Schulman G, Shah S, Zent R, Wolfe M, Blanton W, Bliss C, Farraye F, Huang C, Jacobson B, Lichtenstein D, Lowe R, Mishkin D, Moore T, Oviedo J, Pedrosa M, Schimmel E, Schroy P, Singh S, Tseng C, Fallon M, Arguedas M, Garcia-Gallont R, Kochar R, McGuire B, Mönkemüller K, Neumann H, Sheikh A, Varadarajulu S, Berliner N, Lacy J, Rinder C, Rinder H, Rose M, Seropian S, Tormey C, Torres R, Wang E, Griggs J, Burtness B, Khorana A, Lantz P, Todd R, Smith R, Brooks D, Gopalakrishnan G, Hamdy O, Warren M, Ziegler T, Braunstein G, Barnett P, Herman-Bonert V, Friedman T, Charney P, Carney P, Ehrenthal D, Kottenhahn R, Smith J, Milam D, Starkman J, Stewart A, Greenspan S, Hodak S, Horwitz M, LeBeau S, Roodman G, Moreland L, Agarwal S, Ascherman D, Domsic R, Elliott J, Kao A, Koumpouras F, Kwoh C, Lienesch D, McKinnon-Maksimowicz K, Medsger T, Mohan N, Wing E, Armitage K, Beckwith C, Bobak D, Fairley J, Fulton S, Hileman C, Lange C, Lederman M, Lemonovich T, Lisagaris M, Ray A, Rodriguez B, Salata R, Watkins R, Bradsher R, Griggs R, Berg M, Ciafaloni E, Counihan T, Cheshire W, de los Reyes E, Griggs J, Jackson C, Kerber K, Liu L, Ling G, Lyness J, Lynn D, Marshall F, McCarthy A, Murphy S, Nath A, Roach E, Rogers L, Simon R, Cohen H, Heflin M, Quill T, Holloway R, Hillis L, Lange R. Lead Authors and Contributors. 2010, ix-xix. DOI: 10.1016/b978-1-4160-6109-0.00138-6.
- Rheumatic Manifestations of Systemic DisordersAndreoli and Carpenter’s Cecil Essentials of Medicine, 8th Ed. 2008, pgs. 878-882
- Sjögren’s SyndromeAndreoli and Carpenter’s Cecil Essentials of Medicine, 8th Ed. 2008, pgs. 855-857
- Effects of a novel tylophorine analog on collagen‐induced arthritis through inhibition of the innate immune responseYou X, Pan M, Gao W, Shiah H, Tao J, Zhang D, Koumpouras F, Wang S, Zhao H, Madri JA, Baker D, Cheng Y, Yin Z. Effects of a novel tylophorine analog on collagen‐induced arthritis through inhibition of the innate immune response. Arthritis & Rheumatism 2006, 54: 877-886. PMID: 16508970, DOI: 10.1002/art.21640.
- 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. PMID: 9207132, PMCID: PMC23862.
Clinical Trials
| Conditions | Study Title |
|---|---|
| Immune System | Yale Lupus and Connective Tissue Disease Bio-Repository / Yale Rheumatology Bio-Repository |
| Arthritis | Yale Rheumatology Program Patient Registry and Bio-Repository |
| Diseases of the Kidney & Urinary Tract; Diseases of the Musculoskeletal System | VIBRANT: VIB4920 for Active Lupus Nephritis |