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
| Project: 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. |
Alessandra Franco Associate Professor Dept of Pediatrics UC San Diego Awarded: Matching Funds from the Dean's Office of Medicine to further 2020 Pilot Project
| 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. |
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.
|
Sonya Koo Assistant Clinical Professor Dept of Radiology UC San Diego Awarded: Pilot Project Grant
| Project: Molecular imaging is a promising imaging modality that may have a greater sensitivity to detect active inflammation in osteoarthritis (OA), allowing for the detection of joint inflammation prior to structural changes, and could serve as a biomarker to aid in therapy. Our goal is to develop an optimal protocol for PET-CT imaging in patients with active inflammatory OA utilizing PET-CT radiotracers in the novel context of joint inflammation. Our central hypothesis is that active inflammation in OA will be detectable in the knees with PET-CT and MRI hybrid imaging. |
Mitsue Miyazaki
Adjunct Professor Dept of Radiology UC San Diego
Awarded: Matching Funds from the Department of Radiology to further 2020 Pilot Project
| 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 histologic and transcriptional analyses. |
Yu Yamaguchi Professor Sanford-Burnham Prebys
Medical Research Institute
Awarded: Matching Funds from Sanford Burnham Prebys Institute to further 2020 Pilot Project
| 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. |