A5077147032- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Cellular Mechanics and Interactions
- T-cell and B-cell Immunology
- Advanced Fluorescence Microscopy Techniques
- Cell Image Analysis Techniques
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- Advanced Electron Microscopy Techniques and Applications
- Neonatal Respiratory Health Research
- Cell death mechanisms and regulation
- Cell Adhesion Molecules Research
- Force Microscopy Techniques and Applications
- Erythrocyte Function and Pathophysiology
- Lipid metabolism and biosynthesis
- Monoclonal and Polyclonal Antibodies Research
- RNA Research and Splicing
- Cellular transport and secretion
- Acute Myeloid Leukemia Research
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- Connective tissue disorders research
- Genetics and Neurodevelopmental Disorders
- Photosynthetic Processes and Mechanisms
Baylor College of Medicine
2016-2025
Texas Children's Hospital
2016-2025
St. Jude Children's Research Hospital
2022-2024
Wellcome Centre for Cell-Matrix Research
2010-2019
University of Manchester
2010-2019
Columbia University Irving Medical Center
2019
Centre for Inflammation Research
2015-2018
Université Claude Bernard Lyon 1
2006
Centre National de la Recherche Scientifique
2006
Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated cells and associated with a variable clinical spectrum having overlap more common pathophysiologies. HLH difficult diagnose can be part inflammatory syndromes. Here, we identify novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients superimposable features, including neonatal-onset cytopenia dyshematopoiesis, autoinflammation,...
We present an oblique plane microscope (OPM) that uses a bespoke glass-tipped tertiary objective to improve the resolution, field of view, and usability over previous variants. Owing its high numerical aperture optics, this achieves lateral axial resolutions are comparable square illumination mode lattice light-sheet microscopy, but in user friendly versatile format. Given performance, we demonstrate high-resolution imaging clathrin-mediated endocytosis, vimentin, endoplasmic reticulum,...
During development, morphogens pattern tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been inaccessible, so the molecular mechanisms ensuring successful delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised sonic hedgehog (SHH) and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes. We optimized methods to preserve vivo cytonemes...
The glomerulus contains unique cellular and extracellular matrix (ECM) components, which are required for intact barrier function. Studies of the components have helped to build understanding glomerular disease; however, full composition regulation ECM remains poorly understood. We used mass spectrometry-based proteomics enriched extracts a global analysis human in vivo identified tissue-specific proteome 144 structural regulatory proteins. This catalog includes all previously plus many new...
Defective filopodia formation is linked to pathologies such as cancer, wherein actively protruding filopodia, at the invasive front, accompany cancer cell dissemination. Despite wide biological significance, delineating function in complex systems remains challenging and particularly hindered by lack of compatible methods quantify properties. Here, we present FiloQuant, a freely available ImageJ plugin, detect filopodia-like protrusions both fixed- live-cell microscopy data. We demonstrate...
Natural killer (NK) cells are innate immune effectors that lyse virally infected and tumorigenic through the formation of an immunological synapse. Actin remodeling at lytic synapse is a critical requirement for multiple facets cytotoxic function. Activating receptor integrin signaling leads to regulated turnover actin, which required adhesion, sustained signaling, ultimately exocytosis. NK undergo granule exocytosis in hypodense regions pervasive actin network. Although these requirements...
An inherited disorder makes WAVEs The WAVE regulatory complex (WRC) is a multiunit that regulates actin cytoskeleton formation. Although other actin-regulatory proteins modulate human immune responses, the precise role for WRC has not yet been established. Cook et al. studied five patients from four unrelated families who harbor missense variants of gene encoding component HEM1. These presented with recurrent infections and poor antibody along enhanced allergic autoimmune disorders. HEM1 was...
Chimeric antigen receptor T cells (CART) targeting CD19 through CD28.ζ signaling induce rapid lysis of leukemic blasts, contrasting with persistent tumor control exhibited by 4-1BB.ζ-CART. We reasoned that molecular dynamics at the CART immune synapse (CARIS) could explain differences in their rejection kinetics. observed CD28.ζ-CART engaged brief highly lethal CARIS and mastered serial killing, whereas 4-1BB.ζ-CART formed lengthy relied on robust expansion cooperative killing. analyzed...
Natural killer (NK) cell activation triggers sequential cellular events leading to destruction of diseased cells. We previously identified lytic granule convergence, a dynein- and integrin signal-dependent movement lysosome-related organelles the microtubule-organizing center, as an early step in biological process underlying NK cytotoxicity. Why granules converge during cytotoxicity, however, remains unclear. experimentally controlled availability human ligands regulate signaling promote...
Contact sites between lipid droplets and other organelles are essential for cellular energy homeostasis upon metabolic demands. Detection of these contact at the nanometer scale over time in living cells is challenging. We developed a tool kit detecting based on fluorogen-activated bimolecular complementation CONtact sites, FABCON, using reversible, low-affinity split fluorescent protein, splitFAST. FABCON labels with minimal perturbation to organelle interaction. Via we quantitatively...
Talin, vinculin, and paxillin are core components of the dynamic link between integrins actomyosin. Here, we study mechanisms that mediate their activation association using a mitochondrial-targeting assay, structure-based mutants, advanced microscopy. As expected, full-length vinculin talin autoinhibited do not interact with each other. However, contrary to previous models propose critical role for forces driving talin-vinculin association, our data show force-independent relief...
Tenascin‐X is an extracellular matrix protein whose absence leads to Ehlers‐Danlos syndrome in humans, characterized mainly by disorganisation of collagen and elastic fibril networks. After producing recombinant full‐length tenascin‐X mammalian cells, we find that this assembled into disulfide‐linked oligomers. Trimers were the predominant form observed using rotary shadowing. By solid phase interaction studies, demonstrate interacts with types I, III V fibrillar molecules when they are...
Knowledge of how the elastic stiffness a cell affects its communication with environment is fundamental importance for understanding tissue integrity in health and disease. For measurements, it has been customary to quote single parameter quantity, e.g., Young's modulus, rather than minimum two terms tensor required by elasticity theory. In this study, we use independent methods (acoustic microscopy atomic force nanoindentation) characterize properties thus determine constants. This allows...
Sonic Hedgehog (SHH) is a driver of embryonic patterning that, when corrupted, triggers developmental disorders and cancers. SHH effector responses are organized through primary cilia (PC) that grow retract with the cell cycle in response to extracellular cues. Disruption PC homeostasis corrupts regulation, placing significant pressure on pathway maintain ciliary fitness. Mechanisms by which robustness ensured SHH-stimulated cells not yet known. Herein, we reveal crosstalk circuit induced...
Adaptive immunity is critical in eliminating tumors, but cancer-intrinsic factors can subvert this function. Melanoma antigen-A4 (MAGE-A4), a cancer-testis antigen, expressed solid tumors and correlates with poor survival, its role tumorigenesis antitumor remains unclear. We found that expression of MAGE-A4 was highly associated the loss PTEN , tumor suppressor, human non–small cell lung cancers (NSCLC). Here, we show constitutive Pten mouse airway epithelia results metastatic...
Abstract The efficacy of CAR T-cells (CART) in solid tumors is limited by immune inhibition. In our study, we observed that effector cytokines mediated the upregulation PD-L1 immune-checkpoint primary glioblastoma (GBM). To offset inhibitory signal, engineered PD-1 checkpoint reversal receptors (CPR) with a CD28 or 41BB co-stimulatory endodomain and co-expressed them first-generation CD28-containing second-generation HER2-specific (CPR/CART) using bicistronic vectors. We found bipartite...