A5075508548- CAR-T cell therapy research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Advanced Biosensing Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Biotin and Related Studies
- Gene Regulatory Network Analysis
- Neurobiology and Insect Physiology Research
- Bioinformatics and Genomic Networks
- Autism Spectrum Disorder Research
- Memory and Neural Mechanisms
- Advanced Fluorescence Microscopy Techniques
- Immune responses and vaccinations
- Virus-based gene therapy research
- Single-cell and spatial transcriptomics
- 3D Printing in Biomedical Research
- Evolution and Genetic Dynamics
- Machine Learning in Bioinformatics
- Macrophage Migration Inhibitory Factor
- IL-33, ST2, and ILC Pathways
- Transgenic Plants and Applications
- Cancer Immunotherapy and Biomarkers
- Academic Publishing and Open Access
- Neuroscience and Neuropharmacology Research
Dana-Farber Cancer Institute
2018-2022
Broad Institute
2019-2022
Harvard University
2019-2022
Capital University
2022
WinnMed
2018-2020
Mayo Clinic
2013-2019
Mayo Clinic in Arizona
2013-2019
Melanoma is the deadliest form of skin cancer, affecting men more frequently and severely than women. Although recent studies suggest that differences in activity androgen receptor (AR) underlie observed sex bias, little known about AR melanoma. Here we show EGR1 bind to long non-coding RNA SLNCR increase melanoma proliferation through coordinated transcriptional regulation several growth-regulatory genes. ChIP-seq reveals ligand-free enriched on SLNCR-regulated genes genomic occupancy...
Autism spectrum disorders (ASDs) are a heterogeneous group of behaviorally defined and associated with hundreds rare genetic mutations several environmental risk factors. Mouse models specific factors have been successful in identifying molecular mechanisms given factor. However, comparisons among different to elucidate underlying common pathways or define clusters biologically relevant disease subtypes complicated by methodological approaches brain regions examined the labs that developed...
Multiprotein complexes transduce cellular signals through extensive interaction networks, but the ability to analyze these networks in cells from small clinical biopsies is limited. To address this, we applied an adaptable multiplex matrix system physiologically relevant signaling protein isolated a cell line or human patient samples. Focusing on proximal T receptor (TCR) signalosome, assessed 210 pairs of PiSCES (proteins shared detected by exposed surface epitopes). Upon stimulation Jurkat...
Major challenges to chimeric antigen receptor (CAR) T cell therapies include uncontrolled immune activity, off-tumor toxicities and tumor heterogeneity. To overcome these challenges, we engineered CARs directed against small molecules. By conjugating the same molecule distinct tumor-targeting antibodies, show that specific-CAR cells can be redirected different antigens. Such binary switches allow control over degree of CAR activity enables simultaneous targeting multiple tumor-associated We...
Quantitative activity through the TCR-proximal protein network specifies thymic positive versus negative selection.
Abstract Background There is significant interest in the generation of improved assays to clearly identify experimental mice possessing functional vision, a property that could qualify for inclusion behavioral and neuroscience studies. Widely employed current methods rely on mouse responses visual cues reflexes, depth perception, or cognitive memory. However, commonly assessed reflexes can sometimes be ambiguous their expression, while perception are confounded by variation anxiety...
Dynamic protein-protein interactions control cellular behavior, from motility to DNA replication signal transduction. However, monitoring dynamic among multiple proteins in a protein interaction network is technically difficult. Here, we present protocol for Quantitative Multiplex Immunoprecipitation (QMI), which allows quantitative assessment of fold changes based on relative fluorescence measurements Proteins Shared Complexes detected by Exposed Surface epitopes (PiSCES). In QMI, complexes...
Abstract Human immunity exhibits remarkable heterogeneity among individuals, which engenders variable responses to immune perturbations in human populations. Population studies reveal that, addition interindividual heterogeneity, systemic signatures display longitudinal stability within and these may reliably dictate how given individuals respond perturbations. We hypothesize that analyzing relationships at the population level uncover baseline phenotypes correspond with response outcomes...
Dynamic protein-protein interactions control cellular behavior, from motility to DNA replication signal transduction. However, monitoring dynamic among multiple proteins in a protein interaction network is technically difficult. Here, we present protocol for Quantitative Multiplex Immunoprecipitation (QMI), which allows quantitative assessment of fold changes based on relative fluorescence measurements Proteins Shared Complexes detected by Exposed Surface epitopes (PiSCES). In QMI, complexes...
A technique for identifying patient-specific protein complexes reveals altered signaling in T cells from patients with the autoimmune disease alopecia areata.
Abstract Signaling networks and the protein interactions that define them are of great interest, but techniques to assess these in unmanipulated primary human cells limited. We have developed applied a novel technological analytical platform measure proteins shared complexes detected by exposed surface epitopes (PiSCES). Immunoprecipitation reactions performed multiplex using microsphere beads 20+ 210+ distinct pair-wise associations important for T cell antigen receptor signaling. Jurkat...
Abstract In the context of immunity, genomic sequence, epigenetic, and environmental factor diversity combine to propagate variable gene expression immune function among individuals. We hypothesize that we can harness variability across people study molecular phenotypes predict individual responses stimuli. To test this used RNA-Seq derive a set genes whose is stable over time differential healthy in peripheral blood CD4+ cells. This set, which term response signature (MIRS), identifies...
Abstract CD3-delta has a critical role in alpha-beta T cell development; its absence greatly diminishes thymocyte positive selection. Despite this role, mice lacking have low, but reproducible numbers of peripheral cells, indicating that some development occurs independently CD3-delta. These cells developed via selection as evidenced by genetic Major Histocompatibility Complex-dependence, progression to single thymocytes fetal thymic organ culture and the presence functional immune responses...
Abstract T cell receptor signaling involves interactions of various kinases, phosphatases, ubiquitin ligases and adaptor proteins. However, the network-scale protein-protein (PPIs) that mediate signaling, as well key differences between pro-immunogenic (agonist) pro-tolerogenic (antagonist) signals, remain unclear. We have developed a novel method to examine large networks PPIs, multiplex immunoprecipitation measured by flow cytometry (mIP-FCM). Using multiple classes Luminex® microspheres,...
T cells play a central role in our immune system’s responses to infections. Recent promising clinical studies have shown that the system can be ‘engineered’ recognize and kill tumor by binding specific proteins found on cell surface. The use of ‘chimeric antigen receptor’ (CAR) cells, now approved for treatment certain childhood leukemias, exemplify this strategy. success CAR treat leukemias has expanded efforts apply technology solid tumors. METHODS AND We developed directed against...
Abstract Upon positive selection of conventional αβ T cells, CD4+ CD8+ double-positive (DP) cells transition to single-positive (SP) and reduce their responsiveness weak peptide/MHC ligands (affinity threshold conversion, ATC). We report that ATC actually begins prior the completion in DP stage, this checkpoint is where TCRα/CD3δ signaling axis controls selection. dissected OT1 TCR transgenic system conjunction with several different genes whose null mutations block thymic development at...