Our core research mission is to better understand arthritis, autoimmune, and other connective tissue diseases in order to improve diagnosis and therapies, with the ultimate goal of finding ways to cure and prevent these disorders. A major focus of the Division is to define fundamental processes that underlie mechanisms of autoimmunity and how these may ultimately be harnessed for patient benefit. Research strengths within the Division include basic mechanisms of tissue injury and pathogenesis as well as clinical features, natural history, and therapy of systemic sclerosis, systemic lupus erythematosus, polymyositis-dermatomyositis, rheumatoid arthritis, vasculitis, and osteoarthritis.
Cytokines and Autoimmunity
One major focus of research in the division is how the IL-17/Th17 arm of the immune system drives pathogenesis in autoimmunity. Research in this area is conducted in the laboratories of Drs. Sarah Gaffen (Director of Basic Rheumatology Research) and Partha Biswas, both of whom work in a highly collaborative manner using tissue culture systems, mouse models, and human cell systems/samples.
The main focus of the Gaffen lab centers around the cytokine Interleukin-17. T cell derived cytokines are critical for mediating host defense against infectious disease, but they also mediate disease pathology in autoimmunity. A subset of CD4+ T cells, known as “Th17 cells” based on production of IL-17, plays a key role in driving autoimmunity. Conversely, IL-17 plays important roles in fungal immunity particularly in protection against opportunistic infections caused by the commensal yeast Candida albicans. The Gaffen lab studies mechanisms of signal transduction mediated by IL-17, as well as its role in mediating host defense against fungi. IL-17 and its receptor are unique in structure and sequence from other known cytokines, and the Gaffen lab has been a leader in studying signaling pathways mediated by this this novel family of cytokines. In addition, antibodies against IL-17 and its receptor are in clinical trials to treat various autoimmune conditions. Studies in Dr. Gaffen’s lab also focus on the consequences of anti-IL-17 therapy with respect to infection.
Dr. Biswas’s lab aims to understand the cellular and molecular mechanisms involved in the pathogenesis of rheumatoid disorders such as lupus and RA, with a particular focus on: 1) cytokine abnormalitites in Lupus and Rheumatoid Arthritis, with a particular focus on IL-17 and related cytokines; 2) abnormal Th17 and Follicular helper T cells response in lupus and RA; and 3) the role of transcription factor IRF4 in the pathogenesis of lupus and RA.
Dr. Daniela Schwartz studies a cytokine called IL-9, which links allergic and rheumatic diseases through regulation of lymphocytes, eosinophils, and mucosal barrier function. Research in the Schwartz lab is focused on defining the regulation and biological functions of IL-9 in the context of autoimmune and autoinflammatory conditions. She also investigates rare inborn errors of immunity that link allergic, autoimmune, and autoinflammatory pathologies. This includes the monogenic disease haploinsufficiency of A20 (HA20), an inborn error of ubiquitination that can cause severe autoinflammation, autoimmunity, immunodeficiency, and clinical allergy.
The UPMC Lupus Center of Excellence conducts clinical research trials and has a number of NIH-funded and industry-sponsored studies. The UPMC Lupus Center of Excellence also maintains a longitudinal Lupus Registry, which allows for rigorous data collection and storage of biological samples for
Medical Director of the Lupus Center, Andreea Coca, MD, MPH, is interested in the epidemiology of rheumatic diseases, outcome research and quality improvement projects. As the principal investigator for a number of Sjögren’s syndrome and lupus clinical trials, Dr. Coca works closely with uveitis specialists to develop databases and an inception cohort of uveitis and inflammatory eye disease patients.
Jeremy Tilstra, MD, PhD, is active in clinical, translational, and basic research activities, with a specific interest in Systemic Lupus Erythematosus (SLE) and discovering underlying causes of the disease. He is currently the lead for recruitment of SLE and Sjögren’s patients to the microbiome project, which aims to collect both blood and microbiome samples from patients with these autoimmune diseases. These samples will be compiled with a larger patient cohort collected by other researchers at UPMC. These samples will be used to identify similarities and differences of the microbiome between patient populations afflicted with varying diseases. Another research interest is to evaluate how immune cells change once they enter the target organ in the setting of autoimmunity. Dr. Tilstra’s future work will use blood, urine, and residual biopsy samples to determine which factors may be predictive of outcomes in lupus nephritis.
The goal of the University of Pittsburgh Myositis Center mission is to develop better therapies for the treatment of myositis and its complications and to aid in the cure of myositis.
Chester V. Oddis, MD, has been involved in myositis research for over 30 years with a longstanding interest in the epidemiology, clinical features, autoantibody correlations, and treatment of myositis. His research has contributed to a better understanding of inflammatory myopathy and the elucidation of the pathogenesis of this rare autoimmune disease. He has investigated the pulmonary complications of myositis and the treatment of this common problem. As Director of the Myositis Center at the University of Pittsburgh, Dr. Oddis supervises and manages one of the world’s largest clinically and serologically-defined, longitudinal myositis databases which includes over 1000 patients with adult polymyositis, adult dermatomyositis, and overlap myositis disorders.
Rohit Aggarwal, MD, MS, Co-Director of the Myositis Center at the University of Pittsburgh, is an international expert in various forms of myositis and associated interstitial lung disease. His interests include clinical and translational research in myositis and associated interstitial lung disease, including outcome measures and clinical trials. Along with Dr. Oddis, Dr. Aggarwal is instrumental in the development of one of the largest myositis repositories of clinical data and samples in the country with more than 1500 subjects.
Siamak Moghadam-Kia, MD, MPH, has specifically studied the clinical features of dermatomyositis patients possessing a novel autoantibody and its association with interstitial lung disease and survival. His research interests include clinical features and treatment of idiopathic inflammatory myopathies, autoantibodies and biomarkers in idiopathic inflammatory myopathies, and cutaneous manifestations of systemic rheumatic disease.
The UPMC Rheumatoid Arthritis Center participates in clinical and research trials to offer patients innovative therapies. As part of the Accelerating Medicines Partnership (AMP)—a collaboration between the NIH, biopharmaceutical companies, and nonprofit organizations—patients undergoing a medical procedure involving the removal or collection of biological specimens, such as tissues from a joint, are asked as part of their medical care for permission to include samples of these specimens in the Arthritis and Autoimmunity Tissue Bank. The Division is also participating in other NIH-sponsored initiatives, including the Treatments Against RA and Effect on FDG PET-CT (TARGET) Trial, which examines the effect of RA disease modifying drugs (DMARDs) on vascular inflammation, and the Strategy to Prevent the Onset of Clinically-Apparent Rheumatoid Arthritis (StopRA), which uses blood tests to identify healthy individuals who may be at high risk for developing. Additional multi-disciplinary research studies are ongoing and involve metabolomics, Immunochip analysis, and microbiome using the RACER biorepository. A goal of the RA Center leadership is to understand/document the molecular signatures in patients who are in remission and/or low disease activity. Specific pilot projects are underway evaluating regulatory B cells and T helper follicular cells in these patients. Finally, preliminary data is being generated to explore mechanisms of how methotrexate prevents immunogenicity of biologics.
Since his arrival at the University of Pittsburgh in 2013, Yong Hwang, MD, has continued to develop a clinical research program in RA. Dr. Hwang has been actively involved in research developed from the Rheumatoid Arthritis Comparative Effectiveness Research (RACER) registry, as well as a published, peer-reviewed project examining differential response of serum amyloid A (SAA) to different therapies in RA and the value of SAA as a predictor of disease activity. Additionally, he studied the utility of Patient-Reported Outcomes Measurement Information System (PROMIS) for understanding interplay between patient-reported outcome measures and physician driven disease activity measures. Currently, his research is focused on understanding the complex interplay between RA disease activity, patient-reported outcomes and assessing mechanisms, and impact and management of pain in RA. An investigator-initiated study (funded by Pfizer, Inc.), titled as “Subgrouping of Patients with Rheumatoid Arthritis Based on Biophysical and Psychosocial Factors “ is ongoing since September 2016. The objective of this study is to identify subgroups of RA patients with distinct pain, inflammation, and psychosocial factors and to investigate whether there are different treatment responses among subgroups.
The Scleroderma Center (Pitt) has a very active research program. Drs. Lafyatis and Domsic conduct clinical trials to find new treatments for systemic sclerosis and its complications, including skin fibrosis, Raynaud phenomenon, digital ulcers, interstitial lung disease, and pulmonary arterial hypertension.
Dr. Lafyatis’s laboratory is focused on understanding scleroderma, also known as systemic sclerosis, and developing novel therapeutic approaches based on identifying biomarkers of the disease process and utilizing biomarkers in clinical trials. He has utilized a biomarker approach in a clinical trial of fresolimumab (anti-TGF-beta) to show a role for TGF-beta in skin fibrosis associated with systemic sclerosis. His lab is also applying its pharmacodynamic biomarker of skin disease to trials of tocilizumab (trial completed), and C-82 and rilonacept (ongoing). The Lafyatis lab has a particular interest in understanding the mechanisms stimulating the immune response in systemic sclerosis, focusing on innate immune responses leading to fibrosis and vascular injury. Its data show increased expression of interferon responsive genes in circulating monocytes of scleroderma patients, prompting current investigations into the stimulus for this pattern of gene expression and the effect of interferon on fibrosis and vascular injury. Most recently, Dr. Lafyatis has been examining the transcriptome of single cells in the skin and lungs of patients with systemic sclerosis to better understand the changes in gene expression in different immune and connective tissue cell types that lead to disease.
To aid in developing new therapies for systemic sclerosis, Lafyatis lab is studying the pathogenesis through existing murine models, particularly bleomycin-induced skin and lung fibrosis, testing novel therapeutics to clarify the relationship between innate immunity and fibrosis. The goal is to gain insight from these models that will enable us to propose more informative early phase clinical trials, utilizing biomarkers to show target engagement and as a surrogate clinical response.
In translational studies, Dr. Lafyatis investigates fibroblast and macrophage biology in the pathogenesis of systemic sclerosis, working closely with Patrizia Fuschiotti, PhD, who conducts research on the role of T cells in systemic sclerosis. Dr. Fuschiotti’s research interests focus on the cellular and molecular mechanisms of pathogenesis by T cell and T cell-derived cytokines in inflammatory conditions. Particular emphasis is given to the roles played by cytokine IL-13 and its receptors (IL-13Ra1 and IL-13Ra2) in fibrosis, autoimmunity, and cancer. The context of this work has been in human diseases primarily affecting the skin, namely scleroderma (SSc), an autoimmune connective tissue disease whose main clinical feature is fibrosis, and cutaneous T cell lymphoma (CTCL). Dr. Fuschiotti has shown that IL-13 and its molecular pathways are involved in both diseases, acting as a major pro-fibrotic factor in SSc and as an autocrine factor for CTCL. In addition to understanding the underlying mechanisms of pathogenesis, she has also been developing strategies aimed at targeting IL-13 and its molecular pathways for therapeutic relief.
Dr. Domsic leads the Pittsburgh observational study of patients with systemic sclerosis, which over the years has contributed greatly to the medical literature regarding the clinical manifestations of systemic sclerosis. Dr. Domsic’s research focuses on creating risk prediction models to help manage patients, developing improved outcome measures, and clinical trial design.
See also: UPMC Scleroderma Center
The UPMC Center for Vasculitis focuses on providing the best possible care to patients, education and support for families, and access to new treatment options for those suffering from vasculitis, a disease characterized by the inflammation of blood vessels. The University of Pittsburgh is one of 11 academic sites involved with the NIH-funded Vasculitis Clinical Research Consortium (VCRC). We offer innovative research studies for patients with these rare diseases.
Niveditha Mohan, MD, is engaged in clinical trials in vasculitis and autoimmune eye and ear disease.
Sebastian Sattui, MD, MS, is researching disease biomarkers and the treatment outcomes of patients living with vasculitis such as giant cell arteritis, ANCA-vasculitis, as well as polymyalgia rheumatica (PMR). He is also interested in aging-related outcomes of patients living with vasculitis and PMR, as well as other inflammatory conditions. In response to the COVID-19 pandemic, Dr. Sattui also became involved in different COVID-19 related research initiatives including the COVID-19 Global Rheumatology Alliance. His work has focused on identifying the impact of COVID-19 on patients with rheumatic diseases as well the use of immunomodulatory therapy for the treatment of severe COVID-19.
Division of Rheumatology and Clinical Immunology Offices
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