​​Every year we have outstanding awardees with innovative ideas and research techniques regarding the study of arthritis. Below you can see how they are using Pilot Grants and Seed Grants from the MARC to continue their research and expand our knowledge of arthritis and joint pathology.   

2023

Christina Llorente

Project: The multifactorial pathogenesis of Spondylarthritides (SpA) involves genetics, immune responses, and environmental factors, comprising the gut microbiota. The immune system interacts, tolerates, and shapes the intestinal microbiota while monitoring for pathogens. A balanced intestinal homeostasis is essential to prevent intestinal permeability and microbial translocation to the joint. Goblet cells regulate the intestinal immune response by secreting mucin and presenting luminal antigens to lamina propria dendritic cells (LP-DCs) through goblet-cell associated antigen passages (GAPs). This application aims to study the impact of GAPs in the progression of autoimmune spondylarthritis. The ultimate goal is the discovery of new treatments to alleviate and prevent autoimmune spondylarthritis. Specifically, this application, will characterize the role of gut-joint axis in preclinical models of autoimmune spondylarthritis.

Miguel Lopez-Ramirez

Project: ​Inflammation is a significant factor underlying rheumatoid arthritis (RA), the cause of pain anddisabilities in 1% of the general population, but the factors mediating inflammation and joint destruction are not entirely understood.The studies will investigate the genetic and pharmacological disruption of the endothelial KRIT1-HEG1 complex, which can be used to upregulate KLF2 and KLF4 (transcription factors controlling endothelial function) and may therefore attenuate inflammation and permeability of vasculature observed in RA that contributes to joint destruction. The findings from the proposed study will advance our knowledge of the role of endothelial cells in the vasculature during RA. They may ultimately guide the development of novel approaches and therapeutic targets to contain the devastation and pain occurring duringi nflammatory joint diseases.

Will Wang

Project: We are interested in how cells organize and form the knee joint during development, as this provides insights into where stem cells reside in the joint. By understanding how the joint forms at single cell resolution, we will make a map of how to define a stem cell, and how these cells give rise to parts of the joint. In this proposal, we will identify markers of distinct populations of cells in knee joint and use a novel microscopy technology to simultaneously capture ~60 of these markers in each tissue to find how the arrangement of unique cell populations assemble into a functional joint. Moreover, we will develop new computer software to better identify patterns in
the arrangement of cells in the joint. Our map of the developing joint will better inform our understanding of disease processes and inform future studies on which cells are lost or rearranged in arthritic degeneration and aging. For broader impact, the insights and technologies developed in this project are also relevant for discovering patterns in other tissues of the body (e.g., skin, kidneys, intestine, and brain) and could provide new perspectives in understanding degenerative diseases.

2022

Ru Bryan​

Project: Nicotinamide adenine dinucleotide (NAD+) is a key metabolite that serves as a cofactor for numerous enzymes involved in energy metabolic pathways and cellular function. NAD+ levels steadily decline with aging largely due to the increase in NAD+ degradation by CD38, the main mammalian enzyme that consumes NAD+. In our preliminary studies, we found that CD38 expression was increased in human knee OA cartilage, as well as in human chondrocytes challenged with pro-inflammatory cytokine IL-1, correlated with NAD+ decline. Boosting NAD+ levels to delay aging and age-associated diseases appears to be very attractive therapeutic strategy. Several clinical studies revealed that chronic oral supplementation of NAD+ precursor nicotinamide riboside (NR) is well-tolerated, safe, and boosted human NAD+ metabolism in a dose-dependent manner. In this study, we propose to test our translational hypothesis that boosting NAD+ levels through NR supplementation limits/delays age-related spontaneous OA development in mice. The outcome of this study will provide preclinical evidence of using the NR dietary supplement (commercially known as Niagen) for OA.

Saeed Jerban

Project: ​This project aims to use new MRI techniques to characterize knee entheses in psoriatic arthritis (PsA) patients compared with healthy controls. This study will be performed ex vivo and in vivo. We will explore correlations of our MRI measures with histopathology and biomechanical evaluations of ex vivo entheses specimens and correlations with the in vivo patient-reported outcomes. We hypothesize that our MRI techniques will be more sensitive to degeneration in entheses and patient-reported outcomes than conventional MRIs.​

Jesse Jokerst

Project: ​The long-term goal of this work is improved diagnostic insight for arthritis patients as well as accelerated research into the arthritis microenvironment via a special kind of ultrasound called photoacoustics. This is a “light in/sound out” technique that can map and measure the amount of hemoglobin in a three-dimensional volume of tissue; it can also report how much of the hemoglobin is oxygenated. We will now use this technology to answer questions about the role of inflammation and hypoxia in the arthritis microenvironment.
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2021

Ru Bryan​

Project: This project aims to determine if boosting NAD+ levels through dihydronicotinamide riboside (NRH) oral supplementation limits cartilage degradation and development of osteoarthritis, the most common form of arthritis, in mice using an injury-induced OA model.

Jeffrey Esko

Sepsis induced by Staphylococcus aureus triggers extensive remodeling of the vascular proteome in a tissue-specific manner, which led to the discovery of potential novel markers of infection, including a glycoprotein called Proteoglycan 4  and the glycosaminoglycan hyaluronan. The objective of the proposal is to examine the impact of sepsis on remodeling of the vascular proteome in the joint, on the activation of synoviocytes and the release of  proteoglycan 4, hyaluronan, and cytokines into the synovial fluid. The hypothesis is that activation of the synovium results in expression of proteoglycan 4 and hyaluronan and/or their release from the superficial zone of the cartilage.

Hyungseok Jang