A5101756932- Lymphatic System and Diseases
- Immune cells in cancer
- Myofascial pain diagnosis and treatment
- Ubiquitin and proteasome pathways
- Bone health and treatments
- Tendon Structure and Treatment
- Advanced Breast Cancer Therapies
- Mesenchymal stem cell research
- Multiple Myeloma Research and Treatments
- Osteoarthritis Treatment and Mechanisms
- Inflammatory mediators and NSAID effects
- Histone Deacetylase Inhibitors Research
- Bone Metabolism and Diseases
- Cancer-related Molecular Pathways
- Telomeres, Telomerase, and Senescence
- Single-cell and spatial transcriptomics
- Rheumatoid Arthritis Research and Therapies
- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- HER2/EGFR in Cancer Research
- Microtubule and mitosis dynamics
- Spondyloarthritis Studies and Treatments
- Cell Adhesion Molecules Research
- Oxidative Organic Chemistry Reactions
- Bone and Joint Diseases
University of Rochester Medical Center
2018-2025
University of Rochester
2020-2022
Fujian Agriculture and Forestry University
2020
Eli Lilly (United States)
2010-2014
Eli Lilly (Spain)
2007
The G1 restriction point is critical for regulating the cell cycle and controlled by Rb pathway (CDK4/6-cyclin D1-Rb-p16/ink4a). This important because of its inactivation in a majority human tumors. Transition through requires phosphorylation retinoblastoma protein (Rb) CDK4/6, which are highly validated cancer drug targets. We present identification characterization potent CDK4/6 inhibitor, LY2835219. LY2835219 inhibits CDK4 CDK6 with low nanomolar potency, resulting arrest inhibition...
Cellular senescence plays an important role in human diseases, including osteoporosis and osteoarthritis. Senescent cells (SCs) produce the senescence-associated secretory phenotype to affect function of neighboring SCs themselves. Delayed fracture healing is common elderly accompanied by reduced mesenchymal progenitor (MPCs). However, contribution cellular aged has not our knowledge been studied. Here, we used C57BL/6J 4-month-old young 20-month-old mice demonstrated a rapid increase callus...
The synovial lymphatic system (SLS) removes catabolic factors from the joint. Vascular endothelial growth factor C (VEGF-C) and its receptor, VEGFR-3, are crucial for lymphangiogenesis. However, their involvement in age-related osteoarthritis (OA) is unknown. This study was undertaken to determine whether SLS VEGF-C/VEGFR-3 pathway contribute development progression of OA, using a murine model naturally occurring joint disease.
To investigate the roles of synovial lymphatic system in severity and progression joint tissue damage functional responses endothelial cells (LECs) to macrophage subsets, evaluate therapeutic potential proteasome inhibitor bortezomib (BTZ) a mouse model experimental posttraumatic osteoarthritis (OA).C57BL/6J wild-type mice received meniscal ligamentous injury induce knee OA. Lymphangiogenesis was blocked by vascular growth factor receptor 3 (VEGFR-3) neutralizing antibody. Synovial drainage...
A new cascade approach has been developed for the one-pot four-step divergent synthesis of polysubstituted benzofurans and 2H-chromenes, featuring a novel aromatic Claisen rearrangement/Meinwald rearrangement/dehydrative or oxidative cyclization. This method was demonstrated with 39 examples tolerating different substitutions at an epoxide, allylic ether, ring, we showcased its utility first total natural product liparacid in seven steps.
Abstract Introduction. Lymphatic vasculature in mouse joints is difficult to study due its vast anatomical variation. We reported increased lymphatic capillaries post-traumatic OA (PTOA) murine joint based on 2D immunostaining. However, a gap of knowledge with this approach that histology highly subjected histological sampling, which might not be appropriate for variable system such as the vasculature. hypothesize using lightsheet microscopy would reveal detailed structure initial network....
ABSTRACT Bortezomib (Btz) is a proteasome inhibitor approved by the FDA to treat multiple myeloma. It also increases bone volume promoting osteoblast differentiation and inhibiting osteoclastogenesis in mice. However, Btz has severe systemic adverse effects, which would limit its use as anabolic agent. Here, we designed synthesized bone-targeted form of conjugating it bisphosphonate (BP) with no antiresorptive activity. We report that BP-Btz inhibited osteoclast formation resorption...
Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily characterized by synovial inflammation. In this study, it was found traditional Chinese decoction--JuanBi Tang (JBT) could significantly attenuate the severity of both in collagen-induced (CIA) mice and tumor necrosis factor transgenic (TNF-Tg) mice. According to histopathology stain micro-CT score ankle sections, JBT decrease inflammation area reduce bone destruction joint CIA We also demonstrated alleviate synovitis,...
ABSTRACT The risk of osteoporosis is increased in rheumatoid arthritis (RA). Anti-tumor necrosis factor (TNF) therapy has markedly improved the outcomes RA patients but does not improve some reports. This could be a combined result disease severity and other therapeutic agents, such as glucocorticoids that accelerate progression. We evaluated effects anti-TNF on an animal model explored possible mechanisms involved. Six-week-old TNF transgenic (TNF-Tg) mice with early stage erosive were...
The ubiquitin/proteasome system controls the stability of Runx2 and JunB, proteins essential for differentiation mesenchymal progenitor/stem cells (MPCs) to osteoblasts. Local administration proteasome inhibitor enhances bone fracture healing by accelerating endochondral ossification. However, if a short-term repair potential mechanisms involved have yet be exploited. We hypothesize that injury activates in callus, leading elevated protein ubiquitination degradation, decreased MPCs, impaired...
Abstract Dysregulation of the cell cycle, which normally regulates proliferation in response to mitogenic signaling and other extracellular stimuli, is a hallmark cancer. The G1 restriction point primary mechanism controlling cycle progression controlled by CDK4/6 pathway (CDK4/6-cyclin D1-Rb-CDKN2). importance this highlighted inactivation control majority human tumors. Transition through requires phosphorylation Rb CDK4/6, these kinases are considered highly validated cancer drug targets....
Macrophages play critical roles in homeostasis and inflammation. Macrophage polarization to either a pro-inflammatory or anti-inflammatory status is controlled by activating inflammatory signaling pathways. Ubiquitination posttranslational modification that regulates these However, the influence of protein ubiquitination on macrophage has not been well studied. We hypothesized key proteins pathways contributes polarization, which regulated itchy E3 ubiquitin ligase (ITCH), negative regulator...
ABSTRACT Limited treatment options exist for cancer within the bone, as demonstrated by inevitable, pernicious course of metastatic and blood cancers. The difficulty eliminating bone-residing cancer, especially drug-resistant necessitates novel, alternative treatments to manipulate tumor cells their microenvironment, with minimal off-target effects. To this end, bone-targeted conjugate (BP-Btz) was generated linking bortezomib (Btz, an anticancer, bone-stimulatory drug) a bisphosphonate (BP,...
Cellular senescence plays important roles in age-related diseases, including musculoskeletal disorders. Senescent cells (SCs) exert a senescence-associated secretory phenotype (SASP) by producing SASP factors, some of which overlap with factors produced inflammatory (Inf-Cs). However, the differences between SCs and Inf-Cs how they interact each other during fracture repair have not been well studied. Here, we analyzed single cell RNA sequencing data aged mouse callus stromal cells. We...
Skeletal stem/progenitor cells (SSPCs) are critical for fracture repair by providing osteo-chondro precursors in the callus, which is impaired aging. However, molecular signatures of callus SSPCs during aging not known. Herein, we performed single-cell RNA sequencing on 11,957 CD45 - CD31 Ter119 isolated from young and aged mouse calluses. Combining unsupervised clustering, putative makers, DEGs/pathway analyses, major SSPC clusters were annotated as osteogenic, proliferating, adipogenic...