The following grants ended funding within the last 5 years.
Materials to Increase Minority Involvement in Clinical Trials (MIMIC)
Allen Anandarajah, M.D., M.Sc.
This project is a multistage intervention model to increase providers’ referral of minority patients to lupus clinical trials. MIMICT seeks to increase providers’ knowledge, attitudes, self-efficacy, and intentions to refer African-American and Latino patients to lupus clinical trials and decrease patients’ barriers to learning about clinical trial opportunities. (7/1/2018-6/30/2019)
Develop an Interactive Mobile Health Application to Decrease Social Isolation and Improve Participation in Health Activities Among Lupus Patients
Allen Anandarajah, M.D., M.Sc.
This project aims to develop and utilize a smart phone application to promote and engage healthy practices among patients with lupus.
AMP “Accelerating Medicines Partnership in RA and SLE: Cellular Dynamics at the synovium-bone interface in RA”
Jennifer Anolik, M.D., Ph.D.
The purpose of this study is to better understand the interactions between B cells and T cells (types of white blood cells) and how this may affect joint destruction in patients with autoimmune diseases. The National Institutes of Health (NIH) is the funding agency for this study through the Accelerating Medicines Partnership (AMP) initiative. The AMP initiative is a collaboration between the NIH, biopharmaceutical companies, and non-profit organizations. The goal of AMP is to increase the number of new diagnostics and therapies for patients, and to reduce the time and cost of developing these new treatment options. The AMP Network for Rheumatoid Arthritis and Lupus is composed of various sites across the United States and the University of Rochester is a part of this network as a site. (9/24/2014-6/30/2021)
Evaluating the Impact of Novel Inhibitors of Nuclear Pore Export in SLE
Jennifer Anolik, M.D., Ph.D.
The goal of this project is to improve therapy for SLE by delineating an efficacious combination dosing strategy that targets key synergistic pathways in disease pathogenesis. (12/17/2017-6/30/2020)
The Contribution of Renal Epithelial Cells to Innate Interferon Pathways in Lupus Nephritis
Jennifer Barnas, M.D., Ph.D.
This project explores the hypothesis that the activation of innate interferon pathways within the kidney occurs in renal tubule cells and affects their function. Triggers for the release of Type III interferons such as nucleic acid sensing and oxidative stress pathways will be explored in human kidney epithelial cells. The contribution of Type III interferons to the lupus interferon gene signature will be analyzed as it may represent a new pathway that could serve as a therapeutic target. (8/1/2018-7/31/2020)
Contribution of Adipocytes and Adipose Secreted Factors to Fibrosis in Systemic Sclerosis
Benjamin Korman, M.D.
We have demonstrated that loss of intradermal adipose precedes dermal fibrosis in systemic sclerosis, suggesting that deregulated adipose function may be a primary event in fibrosis. The experiments in this proposal will test whether adipocytes are anti-fibrotic by first determining the phenotypic effect of increased or decreased intradermal adipose on fibrosis, and then by addressing the cellular and molecular mechanism(s) by which adipocytes impact fibrosis, particularly adipocyte secreted factors. (8/1/2016-7/31/2021)
Assessment of the Complement Cascade as a Novel Biomarker, Genetic Risk Factor, and Treatment Target for Scleroderma-Associated Pulmonary Arterial Hypertension
Benjamin Korman, M.D.
Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a severe disease that lacks effective biomarkers or specific treatments. The work in this proposal will assess the value of plasma complement levels as a cross-sectional and longitudinal biomarker in SSc-PAH, assess genetic complement variants in SSc-PAH, and assess complement deficiency and its reversal in a mouse model of SSc-PAH. (12/01/2019-12/01/2021)
Elucidating Thy-1's Role in Scleroderma Skin Fibrosis
Benjamin Korman, M.D.
We will use models of cutaneous fibrogenesis to further investigate the role of Thy-1 on cutaneous fibrosis and scleroderma to develop a compelling story that Thy-1 is important both as a marker of disease and in the pathogenesis of fibrosis. In order to establish this, we will use Thy-1 mice reporter mice as means of tracking fibrosis in vivo, assess Thy-1 knockout mice, and use flow cytometry and RNA sequencing to assess subsets of fibroblasts marked by Thy-1 and other molecules to determine fibroblast heterogeneity in SSc skin. (9/16/2019-8/31/2021)
Modulation of TNF-α as Cause and Treatment of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension
Benjamin Korman, M.D.
Our preliminary data shows that connective tissue disease-associated pulmonary artery hypertension patients have increased lung TNF and an altered TNF gene expression profile. Using the novel TNF-Tg animal model, we will address the hypothesis that amelioration of autoimmune mediated vascular dysfunction with anti-inflammatory or anti-TNF therapy with or without vasodilators can reverse PAH hemodynamically and halt vascular remodeling in connective-tissue-disease associated pulmonary arterial hypertension. To do this, we will assess the effectiveness of immunomodulatory therapy with or without vasodilators in altering the natural history of PAH in the TNF-Tg mouse. (01/01/2020-12/31/2020)
Investigator-initiated, Phase II, randomized, withdrawal study of Mycophenolate Mofetil (MMF) in patients with stable, quiescent Systemic Lupus Erythematosus
John Looney, M.D.
(4/1/2019 - 10/31/2019)
Rheum4Science: An Interactive Online Tutorial for Rheumatology Fellows
Bethany Marston, M.D.
The purpose of this research is to convert materials on basic science and clinical research methodology written by experts in the field to consistent, user-friendly, and relevant eLearning modules using best practices for web-based curricula and to evaluate the implementation of the Rheum4Science curriculum in practice using self-determination theory. In addition, the project will Initiate and evaluate the effects of a Rheum4Science social media discussion group. (7/1/2017-6/30/20)
Discovery of Novel Gene and Metabolite Biomarkers to Diagnose Psoriatic Arthritis and Predict Development of Psoriatic Arthritis
Ananta Paine, Ph.D.
The focus of this grant is to find novel blood and serum clinical biomarkers for psoriatic arthritis (PsA) for the presence of disease and to predict psoriasis (Ps) patients at risk to develop PsA. (2019-2020)
Tofacitinib Mediated Modulation of Aquaporin 3 (AQP3) Expressions on Pathogenic Type 17 Cells in Psoriatic Disease
Ananta Paine, Ph.D.
In this proposed work we will study how interleukin-23 (IL-23)-mediated signaling increase expression of aquaporin 3 (AQP3) on Type 17 cells and will further clarify if a small molecule drug, tofacitinib can inhibit the elevated AQP3 expression in pathogenic Type 17 cells in psoriatic disease. (2019-2021)
RO1 “DC-STAMP: Regulator of Osteoclastogenesis and Response Marker in PsA”
Christopher Ritchlin, M.D., M.P.H.
In this grant, we will combine in vitro cellular and molecular, in vivo osteoimmunology, and translational strategies to address how DC-STAMP promotes OC genesis and inflammation, analyze if 1A2 inhibits synovitis and damage; and investigate if DC-STAMP is an early response biomarker in PsA. Results from these studies will provide insights into key mechanisms that underlie inflammatory arthritis and bone damage in the psoriatic joint and will catalyze biomarker discovery. Importantly, we expect our results will reveal therapeutic targets in the DC-STAMP signaling pathway with potential to impede pathologic bone degradation in PsA, osteoporosis and other inflammatory bone and joint disorders. (3/1/16-1/31/2021)
Therapeutic Targeting of Senescent Cells in Lupus
R. John Looney, M.D.
This project explores the hypothesis that patients with lupus have accelerated accumulation of senescent cells and that treatment with senolytic drugs will clear these cells and improve organ function. Studying the effects of these drugs in vitro using patient and lupus mouse model samples will further fundamental insights into the potential role of senolytic drugs in the treatment of lupus. (9/2018-8/2019)
Bone Marrow IFN Beta and Mesenchymal Stromal Cells
R. John Looney, M.D.
The purpose of this research is to examine the expression and function of IFNβ in SLE patients. The investigators will characterize the regulation and unique functional properties of IFNβ in inducing MSC senescence and loss of immunosuppression function. In addition, the research will define the role of intracellular DNA/RNA sensing pathways in the induction of IFNβ in bone marrow and elucidate the effects of overexpression or silencing of key molecules in the signaling pathway including MAVS, STING, and cGAS on MSC IFNβ production. (1/1/2017-12/31/2018)
Karyopharm Therapeutics “Inhibition of nuclear transport in lupus-prone mice: modulation of renal inflammation and damage via depletion of auto-reactive antibody secreting cells”
Jennifer Anolik, M.D., Ph.D.
To develop a novel approach to the treatment of autoimmunity that targets the generation and survival of auto-reactive plasma cells (PCs) via inhibition of nuclear pore export (Selective Inhibition of Nuclear Pore Export=SINE), an approach being applied by Karyopharm Therapeutics to the treatment of hematologic malignancies, including the plasma cell cancer multiple myeloma. (3/1/2016-2/28/2017)
Medimmune Sponsored Research Agreement "B cell- T follicular helper cell interactions in Primary Sjogren's Syndrome"
Jennifer Anolik, M.D., Ph.D.
The purpose of this study is to look at specific white blood cells called T and B cells. T cells help protect your body against infections by secreting proteins that attract other types of white blood cells, called B cells, who can fight infections. In some autoimmune diseases, like PSS, T cells become defective and cause B cells to act differently than they normally would. (4/3/2014-3/31/18)
P01 (NIH/EMORY) “B cells in health and disease: Project 1: ‘Human transitional B cells: homeostasis and function”
Jennifer Anolik, M.D., Ph.D.
The purpose of this study is to better understand the interactions between B cells and T cells (types of white blood cells) and how this may affect joint destruction in patients with autoimmune diseases. The National Institutes of Health (NIH) is the funding agency for this study through the Accelerating Medicines Partnership (AMP) initiative. The AMP initiative is a collaboration between the NIH, biopharmaceutical companies, and non-profit organizations. The goal of AMP is to increase the number of new diagnostics and therapies for patients, and to reduce the time and cost of developing these new treatment options. The AMP Network for Rheumatoid Arthritis and Lupus is composed of various sites across the United States and the University of Rochester is a part of this network as a site. (9/24/2014-5/31/2019)
LCTC "Lupus Clinical Trials Consortium Network"
R. John Looney, M.D.
The purpose of this study is to learn more about lupus and how the disease is treated. The study will look at how your illness develops over time and will examine your symptoms and any damage that results from this disease over time. In addition, the study will look at treatments that are used for lupus and how people respond to various treatments and treatment combinations. The main goal of the study is to improve understanding of the lupus and its treatment. (1/30/2010)