A5020600378- interferon and immune responses
- Cell Image Analysis Techniques
- Lipid Membrane Structure and Behavior
- Lung Cancer Research Studies
- Glioma Diagnosis and Treatment
- Immune cells in cancer
- Cellular transport and secretion
- Viral Infections and Vectors
- Cytokine Signaling Pathways and Interactions
- Receptor Mechanisms and Signaling
- Mosquito-borne diseases and control
- Brain Metastases and Treatment
- RNA Research and Splicing
- Macrophage Migration Inhibitory Factor
- Cancer Research and Treatments
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Cancer Immunotherapy and Biomarkers
- Inflammatory Biomarkers in Disease Prognosis
- Cancer Genomics and Diagnostics
- Advanced Fluorescence Microscopy Techniques
- Lysosomal Storage Disorders Research
- Single-cell and spatial transcriptomics
- Organophosphorus compounds synthesis
- Nanofabrication and Lithography Techniques
Columbia University
2022-2025
Center for Systems Biology
2013-2024
Columbia University Irving Medical Center
2024
Massachusetts General Hospital
2019-2024
Harvard University
2013-2023
National Center on Addiction and Substance Abuse at Columbia University
2023
Boston VA Research Institute
2021
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
2020-2021
Justus-Liebig-Universität Gießen
2003
Centre Alpien de Phytogéographie
1990
Mitotic errors can activate cyclic GMP-AMP synthase (cGAS) and induce type I interferon (IFN) signaling. Current models propose that chromosome segregation generate micronuclei whose rupture activates cGAS. We used a panel of antimitotic drugs to perturb mitosis in human fibroblasts measured abnormal nuclear morphologies, cGAS localization, IFN signaling the subsequent interphase. Micronuclei consistently recruited without activating it. Instead, correlated with formation cGAS-coated...
Abstract Vesicular traffic and membrane contact sites between organelles enable the exchange of proteins, lipids, metabolites. Recruitment tethers to endoplasmic reticulum (ER) plasma is often triggered by calcium. Here we reveal a function for calcium in repression cholesterol export at ER Golgi complex. We show that efflux from stores induced inositol-triphosphate [IP 3 ] accumulation upon loss inositol 5-phosphatase INPP5A or receptor signaling triggers depletion associated Gb3 cell...
Hydrophobic thickness mismatch between integral membrane proteins and the surrounding lipid bilayer can produce deformations. Experiment theory have shown that protein-induced deformations yield energetically favorable bilayer-mediated interactions proteins, large-scale organization of into protein clusters in cell membranes. Within continuum elasticity membranes, energy cost be captured by considering compression expansion hydrophobic core, tension, bending, resulting biharmonic equilibrium...
Introduction Neoadjuvant chemoimmunotherapy has achieved overall survival (OS) benefit for patients with resectable non-small cell lung cancer (NSCLC). Here, we present outcomes after 3 years of follow-up from the first reported study neoadjuvant atezolizumab+chemotherapy. Methods This open-label, multicenter single-arm investigator-initiated phase II conducted at three US hospitals tested up to four cycles atezolizumab, carboplatin, and nab-paclitaxel prior surgery. Major pathological...
We screened a library of bioactive small molecules for activators and inhibitors innate immune signaling through IRF3 NFkB pathways with the goals advancing pathway understanding discovering probes immunology research. used high content screening to measure translocation from cytoplasm nucleus in primary human macrophages; these transcription factors play critical role activation STING other pro-inflammatory pathways. Our activator screen yielded diverse set hits that promoted nuclear and/or...
Recent advances in the field of intravital imaging have for first time allowed us to conduct pharmacokinetic and pharmacodynamic studies at single cell level live animal models. Due these advances, there is now a critical need automated analysis data. To address this, we began by surveying common thresholding methods determine which would be most appropriate identifying fluorescently labeled drugs imaging. We then developed segmentation algorithm that allows semi-automated data level....
Abstract Experiments have revealed that membrane proteins can form two-dimensional clusters with regular translational and orientational protein arrangements, which may allow cells to modulate function. However, the physical mechanisms yielding supramolecular organization collective function of remain largely unknown. Here we show bilayer-mediated elastic interactions between yield distinctive lattice architectures provide a link architecture Using mechanosensitive channel large conductance...
Abstract Introduction: Neoadjuvant chemoimmunotherapy is promising in improving outcomes for patients with resectable lung cancer the phase III setting, though data are immature at this time overall survival (OS). Here, we present after 3 years of follow-up from first reported study neoadjuvant immunotherapy + chemotherapy population. Methods: This open-label, multi-center single-arm investigator-initiated II was conducted three hospitals USA. atezolizumab, carboplatin, and nab-paclitaxel...
Infectious diseases caused by viral pathogens exacerbate health care and economic burdens. Numerous biomolecules suppress the human innate immune system, enabling viruses to evade an response from host.
Abstract STING, an ER resident cyclic dinucleotide (CDN) receptor, plays important role in innate immune response signaling. Upon binding to CDNs, it activates the TBK1-IRF3 signaling axis, which stimulates gene expression including interferon beta. We hypothesized that localization of STING reflects a for calcium mobilization its To test this hypothesis, we treated mouse cells with two agonists, synthetic drug DMXAA and natural ligand, GMP-AMP (cGAMP), measured intracellular calcium. Both...
The receptor tyrosine kinase inhibitor, Tie2, has significant roles in endothelial signaling and angiogenesis is relevant the pathophysiology of several diseases. However, there are relatively few small molecule probes available to study making evaluation its activity vivo difficult. Recently, it was discovered that rebastinib (DCC-2036) a potent Tie2 inhibitor. We hypothesized fluorescent derivatives could be used as imaging agents for Tie2. On basis crystallography structures, we...
Summary Mitotic errors can activate cGAS and induce type-I interferon (IFN) signaling. Current models propose that chromosome segregation generate micronuclei whose rupture activates cGAS. We used a panel of anti-mitotic drugs to perturb mitosis in fibroblasts measured abnormal nuclear morphologies, localization IFN signaling the subsequent interphase. Micronuclei consistently recruited without activating it. Instead, correlated with formation cGAS-coated chromatin bridges were selectively...
Multiple potent covalent inhibitors for mutant KRAS G12C have been described and some are in clinical trials. These small molecule potentially allow companion imaging probe development, thereby expanding the chemical biology toolkit to investigate biology. Herein, we synthesized tested a series of fluorescent drugs (CID) G12C, using two scaffolds, ARS-1323 AMG-510. We created four derivatives each by attaching BODIPY dyes. found that (BODIPY FL TMR) bind can be used biochemical binding...
Abstract The interaction between gliomas and the immune system is poorly understood thus hindering development of effective immunotherapies for glioma patients. response highly variable during tumor development, affected by therapies such as surgery, radiation, chemotherapy. Currently, analysis these local changes difficult due to poor accessibility high-morbidity sampling. In this study, we developed a model repeat-biopsy in mice study immunological over time. Using fine needle biopsy were...