Pilot Grant Awardees

​​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.   


Christina Llorente

Assistant Professor, Dept of Medicine, UC San Diego
Awarded: Pilot Project Grant

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

Assistant Professor, Dept of Medicine, UC San Diego
Awarded: Pilot Project Grant

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

Assistant Professor, Sanford Burnham Prebys Medical Discovery Institute
Awarded: Pilot Project Grant

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.


Ru Bryan​

Professor, Dept of Medicine, UC San Diego
Awarded: Pilot Project Grant

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

Assistant Project Scientist, Dept of Radiology, UC San Diego 
Awarded: Pilot Project Grant

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

Professor, Dept of Nanoengineering, UC San Diego
Awarded: Pilot Project Grant

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.



Ru Bryan​

Professor, Dept of Medicine, UC San Diego
Awarded: Pilot Seed Grant

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

Professor, Dept of Cellular and Molecular Medicine, UC San Diego
Awarded: Pilot Seed Grant

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

Associate Project Scientist, Dept of Radiology, UC San Diego
Awarded: Pilot Project Grant
Project:The osteochondral junction (OCJ) region is commonly defined to include the deep radial uncalcified cartilage, tidemark, calcified cartilage, and subchondral bone plate, functioning to absorb mechanical stress, which is commonly associated with the pathogenesis of osteoarthritis. However, MRI of the OCJ region is difficult due to the short transverse relaxation times (i.e., short T2 or T2*), which result in little or no signal with conventional MRI. The goal of this study is to develop and optimize a 3D adiabatic inversion recovery prepared fat saturated ZTE (IR-FS-ZTE) sequence for direct volumetric morphological imaging and quantitative T2* and T1 mapping of the OCJ, to validate the signal sources, and finally develop translational 3D IR-FS-ZTE techniques for OCJ imaging in vivo.


Alessandra Franco

Associate Professor, Dept of Pediatrics, UC San Diego
Awarded: Pilot Project Grant

Project: Natural regulatory T cells (Treg) that recognize the heavy constant region of IgG (Fc) are important in down-regulating inflammation. We defined the fine specificity of these Tregs and mapped the immunodominant peptides in healthy donors and patients with Rheumatoid Arthritis (RA). In RA, the Treg response to the Fc has been found compromised because of the inefficient entry in antigen presenting cells (APC). Myeloid dendritic cells, specifically cDC2, are the most efficient APC in presenting the Fc to Treg. The grant explores the role of Fcg receptors II and III, which are often mutated in RA, jeopardizing the Fc entry for antigen processing and presentation to Treg.

Mitsue Miyazaki

Adjunct Professor, Dept of Radiology, UC San Diego
Awarded: Pilot Project Grant

Project: Osteoarthritis (OA) is a prevalent degenerative joint disease affecting many joints of the body, including the knee. While current MR imaging evaluation of the knee has focused on morphologic assessment, and newer quantitative techniques have focused on biochemical interrogation, to a varying degree of success. There currently does not exist an MR technique that simultaneously addresses both at macromolecular evaluation, such as proteoglycans in cartilage extracellular matrix, as well as short T2 acquisition needed to accurately image deep layer cartilage, extracellular matrix, as well as short T2 acquisition needed to accurately image deep layer cartilage, meniscus, and tendons/ligaments. This is a study to demonstrate feasibility ofmacromolecule exchange protons using Z-spectrum analysis of protons (ZAP) MRI and to gather preliminary data providing evidence of sensitivity of ZAP MRI to OA, and how ZAP MR measures correlate with conventional quantitative MRI, as well as reference measures of biomechanical, biochemical, and cellular changes from histological and transcriptional analyses. 

Yu Yamaguchi

Professor, Sanford-Burnham Prebys Medical Research Institute
Awarded: Pilot Project Grant

Project: Hyaluronan is a major component of cartilage. Interestingly, the half-life of hyaluronan is extremely short and its homeostasis is maintained by rapid turnover, suggesting that dysregulation of not only the anabolic but also the catabolic arm of hyaluronan metabolism can be a cause of cartilage degeneration and joint disorders. In this pilot project, we will investigate the role of TMEM2, the first membrane-anchored hyaluronidase identified in mammalian cells, in cartilage homeostasis and degeneration using a TMEM2 mutant mouse model.


Elsa Sanchez-Lopez

Assistant Project Scientist, Dept of Pharmacology, UC San Diego
Awarded: Pilot Project Grant

Project: Chronic macrophage activation and prolonged inflammatory response underlies most inflammatory and autoimmune diseases. Metabolic reprograming and lipidomic remodeling are hallmarks of immune cell activation, and in particular, choline uptake and utilization shape macrophage-dependent inflammation. We are focused in how choline availability and utilization influence macrophage phenotype and function in human inflammatory diseases by using human biopsies, mouse models and cell cultures.

Nisarg Shah

 Assistant Professor, Dept of Nanoengineering, UC San Diego
Awarded: Pilot Grant Award

Project: Dr. Shah's research group develops cell-instructive biomaterials, organized to function as chemical and molecular regulators to drive immune cell specificities towards restoring the immune function of negative feedback. In rheumatoid arthritis (RA), the loss of immune self-regulation is an important contributor to the pathogenesis of the disease. The MARC pilot project grant provided crucial support and collaborations for testing biomaterials-mediated restoration of disease-relevant regulatory immune cell subsets, towards developing a durable therapy for RA.

Meng Zhao

Assistant Professor, Arthritis and Clinical Immunology Program, University of Oklahoma
Awarded: Pilot Project Grant

Project: Innate like T cells, including iNKT cells, MAIT cells and gamma delta T cells are a group of fast responding T lymphocytes. Our previous study showed iNKT cells prevent the development of severe autoimmune arthritis. The MARC pilot enabled us to explore the role of MAIT cells, another kind of innate like T in the pathogenesis of rheumatoid arthritis.