A5016756327- Gut microbiota and health
- Galectins and Cancer Biology
- Vector-borne infectious diseases
- Macrophage Migration Inhibitory Factor
- Viral Infections and Vectors
- Probiotics and Fermented Foods
- Mosquito-borne diseases and control
- Monoclonal and Polyclonal Antibodies Research
- Insect and Pesticide Research
- Chronic Lymphocytic Leukemia Research
- Clostridium difficile and Clostridium perfringens research
- Protein Tyrosine Phosphatases
- Inflammasome and immune disorders
- PI3K/AKT/mTOR signaling in cancer
- Viral Infections and Immunology Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Glycosylation and Glycoproteins Research
- Adrenal Hormones and Disorders
- T-cell and B-cell Immunology
- RNA and protein synthesis mechanisms
- Immune Cell Function and Interaction
- Systemic Lupus Erythematosus Research
- GDF15 and Related Biomarkers
Yale University
2017-2024
University of New Haven
2020
University of California, Berkeley
2015
Howard Hughes Medical Institute
2015
QB3
2015
California Institute of Technology
2014
Center for Rheumatology
2013
Bruton's tyrosine kinase (Btk), a Tec-family kinase, is essential for B-cell function. We present crystallographic and biochemical analyses of Btk, which together reveal molecular details its autoinhibition activation. Autoinhibited Btk adopts compact conformation like that inactive c-Src c-Abl. A lipid-binding PH-TH module, unique to Tec kinases, acts in conjunction with the SH2 SH3 domains stabilize conformation. In addition expected activation by membranes containing phosphatidylinositol...
Autoantibodies that recognize extracellular proteins (the exoproteome) exert potent biological effects but are challenging to detect. Here, we developed rapid antigen profiling (REAP), a high-throughput technique for the comprehensive discovery of exoproteome-targeting autoantibodies. Patient samples applied genetically barcoded yeast surface display library containing 2,688 human proteins. Antibody-coated isolated, and sequencing barcodes is used identify displayed antigens. To benchmark...
Abstract BACKGROUND: High levels of ULK1/2-mediated macroautophagy (autophagy) are associated with immunologically cold tumors that respond poorly to therapy. Increased autophagy results in decreased antigen processing and presentation (APP) mediated by autophagosomal degradation neoantigen-generating immunoproteasomes MHC-I. Here, we demonstrate inhibition restores APP increases antigen-specific CD8+ T-cell cytotoxicity. METHODS: Levels machinery were assessed at baseline after ULK1/2 using...
Increased airway smooth muscle (ASM) contractility and the development of hyperresponsiveness (AHR) are cardinal features asthma, but signaling pathways that promote these changes poorly understood. Tyrosine phosphorylation is tightly regulated by opposing actions protein tyrosine kinases phosphatases, little known about whether phosphatases influence AHR. Here, we demonstrate genetic inactivation receptor-like phosphatase J (Ptprj), which encodes CD148, protected mice from increased AHR in...
Lyme disease, the most common vector-borne illness in North America, is caused by spirochete Borrelia burgdorferi . Infection begins skin following a tick bite and can spread to hearts, joints, nervous system, other organs. Diverse host responses influence level of B infection mice humans. Using systems biology approach, we examined potential molecular interactions between human extracellular secreted proteins A yeast display library expressing 1031 was probed against 36 isolates sensu lato...
Significance We describe the discovery and analyses of a previously uncharacterized protein, termed Liat1 (ligand Ate1), which has been identified because its interactions with Ate1 arginyltransferase, component N-end rule pathway protein degradation. All vertebrates contain proteins similar to mouse Liat1. Remarkably, some primates tandem repeats 10-residue sequence, whereas other mammals single copy this motif. Quantities these are, in general, different primates. For example, there are 4,...
The
Relapsing fever, caused by diverse Borrelia spirochetes, is prevalent in many parts of the world and causes significant morbidity mortality. To investigate pathoetiology relapsing we performed a high-throughput screen Borrelia-binding host factors using library human extracellular secretory proteins identified CD55 as novel binding partner crocidurae persica, two agents fever Africa Eurasia. present on surface erythrocytes, carries Cromer blood group antigens, protects cells from...
Abstract Autoantibodies that recognize extracellular proteins (the “exoproteome”) exert potent biological effects but have proven challenging to detect with existing screening technologies. Here, we developed Rapid Extracellular Antigen Profiling (REAP) as a technique for comprehensive, high-throughput discovery of exoproteome-targeting autoantibodies. With REAP, patient samples are applied genetically-barcoded library containing 2,688 human displayed on the surface yeast. Antibody-coated...
Borrelia burgdorferi causes Lyme disease, the most common tick-transmitted illness in North America. When Ixodes scapularis feed on an infected vertebrate host, spirochetes enter tick gut along with bloodmeal and colonize vector. Here, we show that a secreted protein, I. scapularisprotein disulfide isomerase A3 (IsPDIA3), enhances B. colonization of gut. ticks which ispdiA3 has been knocked down using RNA interference have decreased spirochete after engorging burgdorferi-infected mice....
Abstract BACKGROUND: Inactivating mutations and deletions in STK11 are present 9-20% of NSCLC result immunologically cold tumors that respond poorly to therapy, despite having a high tumor mutational burden neoantigen load. associated with higher levels ULK1/2-mediated macroautophagy, resulting localization MHC-I autophagosomes lysosomes leading its degradation decreased antigen presentation. Knockdown ULK1/2 can restore surface highly autophagic cell lines. Here, we show inhibition...
<h3>Background</h3> Interferon gamma (IFNG) is a cytokine that essential for anti-tumor immune activity in variety of tumor models and settings. IFNG induces responses important immunity, such as antigen processing presentation molecules, but can also induce immunosuppressive molecules PD-L1. additionally exhibits direct growth inhibition or apoptosis-inducing potential some cell Regulation sensing cells therefore represents mechanism to enhance immunity. STUB1 ubiquitin ligase has been...