A5012348799- Immune Response and Inflammation
- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Neonatal and Maternal Infections
- interferon and immune responses
- Pediatric health and respiratory diseases
- Advanced Proteomics Techniques and Applications
- Pneumonia and Respiratory Infections
- Antimicrobial Peptides and Activities
- Phytochemical compounds biological activities
- Protein Kinase Regulation and GTPase Signaling
- Metabolomics and Mass Spectrometry Studies
- Mass Spectrometry Techniques and Applications
- Peptidase Inhibition and Analysis
- Insect Pest Control Strategies
- Synthesis and Catalytic Reactions
- Monoclonal and Polyclonal Antibodies Research
- Catalytic C–H Functionalization Methods
- Advanced Drug Delivery Systems
- Signaling Pathways in Disease
- Complement system in diseases
- HIV Research and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
- Metabolism and Genetic Disorders
- Multiple Myeloma Research and Treatments
Yale Cancer Center
2023-2025
Yale University
2020-2025
Shanghai Institute of Organic Chemistry
2024
Chinese Academy of Sciences
2013-2024
Tsinghua University
2017-2021
Whitney Museum of American Art
2021
University of Colorado Boulder
2017-2020
Center for Life Sciences
2020
Peking University
2020
Shanghai Pulmonary Hospital
2013
Microtubule-associated protein tau is essential for microtubule assembly and stabilization. Hyperphosphorylation of the microtubule-associated plays an important pathological role in development Alzheimer's disease other tauopathies. In vivo studies using kinase inhibitors suggest that reducing phosphorylation levels has therapeutic potential; however, such approaches showed limited benefits. We sought to further develop our targeting chimera (PhosTAC) technology specifically induce...
Protein phosphorylation, which regulates many critical aspects of cell biology, is dynamically governed by kinases and phosphatases. Many diseases are associated with dysregulated hyperphosphorylation proteins, such as retinoblastoma protein in cancer. Although kinase inhibitors have been widely applied the clinic, growing evidence off-target effects increasing drug resistance prompts need to develop a new generation drugs. Here, we propose proof-of-concept study phosphorylation targeting...
During HIV infection, cell-to-cell transmission results in endosomal uptake of the virus by target CD4+ T cells and potential exposure viral ssRNA genome to Toll-like receptors (TLRs). TLRs are instrumental activating inflammatory responses innate immune cells, but their function adaptive is less well understood. Here we show that synthetic ligands TLR8 boosted cell receptor signaling, resulting increased cytokine production upregulation surface activation markers. Adjuvant stimulation, not...
We recently developed a heterobifunctional approach [phosphorylation targeting chimeras (PhosTACs)] to achieve the targeted protein dephosphorylation (TPDephos). Here, we envisioned combining inhibitory effects of receptor tyrosine kinase inhibitors (RTKIs) and active by phosphatases dual inhibition kinases. report an example phosphatase–based TPDephos effective epidermal growth factor (EGFR) dephosphorylation. also used phosphoproteomic approaches study signaling transductions affected...
TLR8 is an endosomal sensor of RNA degradation products in human phagocytes, and involved the recognition viral bacterial pathogens. We previously showed that primary monocytes monocyte derived macrophages, senses entire Staphylococcus aureus Streptococcus agalactiae (group B streptococcus, GBS), resulting activation IRF5 production IFNβ, IL-12p70, TNF. However, quantitative qualitative impact for sensing bacteria have remained unclear because selective inhibitors been unavailable. Moreover,...
Abstract The serine/threonine kinase AKT is a central node in cell signaling. While aberrant activation underlies the development of variety human diseases, how different patterns AKT-dependent phosphorylation dictate downstream signaling and phenotypic outcomes remains largely enigmatic. Herein, we perform systems-level analysis that integrates methodological advances optogenetics, mass spectrometry-based phosphoproteomics, bioinformatics to elucidate intensity, duration, pattern Akt1...
<title>Abstract</title> Phosphorylation targeting chimeras (PhosTACs) recruit phosphatases to dephosphorylate target proteins by proximity-induced protein interactions. However, recruiting a phosphatase subunit or holoenzyme using small molecules without compromising its activity adversely disturbing cellular function remains challenging. In addition, many do not have favorable activator binder currently. To overcome these limitations, here, we report an adapted mode of action, named...
Synthesis of a withasomnine-inspired library which shows anticancer reactivities and COX-2 inhibition <italic>via</italic> an intramolecular dehydrogenative cyclization process.
Abstract We recently showed that TLR8 is critical for the detection of Gram-positive bacteria by human monocytes. Here, we hypothesized and complement together regulate antibacterial responses in blood. Anticoagulated blood was treated with selective inhibitors and/or C5, then challenged live Streptococcus agalactiae (Group B streptococcus, GBS), Staphylococcus aureus, or Escherichia coli. Cytokine production, plasma membrane permeability, bacterial survival, phagocytosis, activation...
SUMMARY Understanding how proteins in different mammalian tissues are regulated is central to biology. Protein abundance, turnover, and post-translational modifications like phosphorylation, key factors that determine tissue-specific proteome properties. However, these properties challenging study across remain poorly understood. Here, we present Turnover-PPT , a comprehensive resource mapping the abundance lifetime of 11,000 40,000 phosphosites eight mouse various brain regions, using...
Toll-like receptor 8 (TLR8) is a pattern recognition that senses RNA degradation products and initiates immune responses. TLR8 overactivation associated with autoimmune diseases. Herein, we describe the evaluation validation of antagonists in HEK-Blue cells via secreted embryonic alkaline phosphatase (SEAP) assay, WST ITC immunoblotting. These assays can facilitate development antagonists; this protocol also be adapted to analyze agonists for other TLRs. For complete details on use execution...
Abstract Many diseases, including cancer, stem from aberrant activation and overexpression of oncoproteins that are associated with multiple signaling pathways. Although proteins catalytic activity able to be successfully drugged, the majority other protein families, such as transcription factors, remain intractable due their lack ligandable sites. In this study, we report development TRAnscription Factor TArgeting Chimeras (TRAFTACs) a generalizable strategy for targeted...
Phosphorylation is one of the most important post-translational modifications (PTMs) proteins, governing critical protein functions. Most human proteins have been shown to undergo phosphorylation, and phosphoproteomic studies widely applied due recent advancements in high-resolution mass spectrometry technology. Although experimental workflow for phosphoproteomics has well-established, it would be useful optimize summarize a detailed, feasible protocol that combines data-independent...