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.
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.
Education, Graduate; Lupus Erythematosus, Systemic; Lupus Nephritis; Therapeutics; Biomarkers; Randomized Controlled Trials as Topic