Grant Funding
Many of the University of Rochester Allergy, Immunology and Rheumatology faculty have active basic research grants that support innovative approaches to the study of the etiology and treatment of autoimmune diseases. In addition, some of these faculty conduct translational research linking clinical trials to their basic research.
Jennifer Anolik, MD, PhD
Although new treatments have improved outcomes in rheumatoid arthritis (RA), disability remains high, most patients have ongoing disease activity, and lasting remissions are rare. A major gap in the field is the elusive identity of pathogenic cells driving persistent inflammation and bone erosion. Our lab focuses on the identification of pathogenic B cell subsets in RA, which might drive persistent and aggressive disease. We recently identified a subset of B cells expressing the classic T cell lineage defining transcription factor T-bet enriched in the RA synovium that we propose mediates B cell-driven bone activation of osteoclasts, inhibition of osteoblasts, and promotion of pro-inflammatory monocytes. We will use deeply characterized RA patient cohorts, high- resolution single cell transcriptomic and spatial analysis of joint target tissue, and novel animal models to track T bet B cells and selectively and conditionally delete T-bet in B cells of mice with arthritis
Jennifer Anolik, MD, PhD and Javier Rangel-Moreno, PhD
This project, funded by the Lupus Research Alliance, will investigate the ability a class of drugs currently approved to treat type 2 diabetes – sodium-glucose cotransporter-2 (SGLT2) inhibitors – to improve lupus nephritis and reduce kidney damage and improve kidney function. It will explore the complex interactions between nephritis disease progression, rogue immune cells stimulating lupus progression, tissue hypoxia, and kidney injury.
Jennifer Anolik, M.D., Ph.D.
The goal of the new grant is to marshal in transformative, high-dimensional technology that has been developed in the last decade, such as transcriptomic and genomic approaches, and apply those to patient-focused research. The prior AMP grant allowed researchers to isolate single cells for target tissue such as joint and kidney for the first time for research in a ‘disease deconstruction’ approach, and this next stage of the project will incorporate ‘disease reconstruction’—looking spatially within tissue to determine what cells are next to each other, how they communicate, and how environmental influences affect the cells and/or the disease. (3/2022)
Jennifer Anolik, M.D., Ph.D.
Understanding the diversity of clinical phenotypes and mechanistic origins of pain in inflammatory arthritis is a major unmet need in the field. The relationship of synovial cellular and molecular signatures and their correlation with pain coupled with the impact of residual pain on treatment response require new investigative strategies. Goals of this grant are to define pain phenotypes associated with peripheral and central mechanisms of pain in patients with rheumatoid arthritis and psoriatic arthritis and identify novel mediators of pain in the RA and PsA synovium including the relationship between pain and synovial tissue innervation using single cell transcriptiomic approaches and novel 3-dimensional tissue staining.
Jennifer Barnas, MD, PhD
The long-term objective of the study is to understand signals that regulate the development of ABC and autoreactive PC in lupus nephritis patients in hopes of identifying new therapeutic targets.
In the Katz R01, we are looking to evaluate the hypothesis that the "don't eat me" molecule CD47 is critical to RA pathogenesis and that reduction of CD47 signaling will reduce or reverse inflammatory arthritis via effects in immune and mesenchymal cells. We will investigate this by first evaluating the cell specific implications of CD47 signaling via using histologic analysis from patient biopsies, single cell RNA-sequencing, and 3D organoid cultures derived from RA and OA patient samples. We will then assess whether CD47 is required for inflammatory arthritis and bone erosion by evaluating CD47 knockout in different mouse models of inflammatory arthritis. Finally, we will use the organoid model to screen combination therapies using anti-CD47 antibodies and biologic treatments and validate the most promising treatment strategies in vivo.
Benjamin Korman, M.D.
This project focuses on identifying how altered expression of tumor necrosis factor (TNF) leads to a pulmonary vascular phenotype. The grant looks to understand whether pathologic processes known to induce pulmonary hypertension in other systems occur in endothelial cells, to perform single-cell transcriptomics to understand which populations of cells are altered and how, and then to address the relative importance of the receptors TNFR1 and TNFR2 on the process. (4/1/2020-3/31/2022)
Bethany Marston, M.D.
The purpose of this award is to provide education and training opportunities that will build the rheumatology workforce to meet the growing demand for rheumatologic care. (7/1/2020)
Christopher Ritchlin, M.D., M.P.H.
(3/2022)
Christopher Ritchlin, M.D., M.P.H.
The goal of the new grant is to marshal in transformative, high-dimensional technology that has been developed in the last decade, such as transcriptomic and genomic approaches, and apply those to patient-focused research. The prior AMP grant allowed researchers to isolate single cells for target tissue such as joint and kidney for the first time for research in a ‘disease deconstruction’ approach, and this next stage of the project will incorporate ‘disease reconstruction’—looking spatially within tissue to determine what cells are next to each other, how they communicate, and how environmental influences affect the cells and/or the disease.