A5001281792- Single-cell and spatial transcriptomics
- Monoclonal and Polyclonal Antibodies Research
- Cell Image Analysis Techniques
- Immunotherapy and Immune Responses
- Endoplasmic Reticulum Stress and Disease
- Glycosylation and Glycoproteins Research
- Cancer Immunotherapy and Biomarkers
- Heat shock proteins research
- RNA and protein synthesis mechanisms
- Cancer Research and Treatments
- Cancer-related Molecular Pathways
- Immune cells in cancer
- Mathematical Biology Tumor Growth
- thermodynamics and calorimetric analyses
- Cervical Cancer and HPV Research
- Bioinformatics and Genomic Networks
- Gene Regulatory Network Analysis
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Data Visualization and Analytics
- vaccines and immunoinformatics approaches
- Alzheimer's disease research and treatments
- Amyotrophic Lateral Sclerosis Research
- Ferroptosis and cancer prognosis
Sanofi (United States)
2023-2024
Harvard University
2010-2024
Sanofi (Mexico)
2024
Sanofi (France)
2024
Brigham and Women's Hospital
2019-2023
Center for Systems Biology
2010-2023
Harvard University Press
2022
Whitehead Institute for Biomedical Research
2016-2020
Center for Cancer Research
2019
CD8 T cell responses against different tumor neoantigens occur simultaneously, yet little is known about the interplay between and its impact on function control. In mouse lung adenocarcinoma, we found that immunodominance established in tumors, wherein expansion predominantly driven by antigen most stably binds MHC. cells responding to subdominant antigens were enriched for a TCF1+ progenitor phenotype correlated with response immune checkpoint blockade (ICB) therapy. However, did not...
Homo-oligomerization is found in many biological systems and has been extensively studied vitro. However, our ability to quantify understand oligomerization processes cells still limited. We used fluorescence correlation spectroscopy mathematical modeling measure the dynamics of tetramers formed by tumor suppressor protein p53 single living cells. Previous vitro studies suggested that basal conditions all molecules are bound dimers. resting present a mix oligomeric states with large...
Abstract Early characterization of drug targets associated with disease can greatly reduce clinical failures attributed to lack safety or efficacy. As single-cell RNA sequencing (scRNA-seq) human tissues becomes increasingly common for profiling, the insights obtained from this data could influence target selection strategies. Whilst use scRNA-seq understand biology is well established, impact in increasing probability candidate therapeutic successfully advance research clinic has not been...
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron loss. Microglia and astrocyte-driven neuroinflammation prominent in ALS, but the cell state dynamics pathways driving remain unclear. We performed single-nucleus RNA sequencing of ALS spinal cords identified altered glial states, including increased expression inflammatory activation markers. Many these signals converged on inflammation death regulator receptor-interacting protein...
Abstract In this data descriptor, we document a dataset of multiplexed immunofluorescence images and derived single-cell measurements immune lineage other markers in formaldehyde-fixed paraffin-embedded (FFPE) human tonsil lung cancer tissue. We used tissue cyclic (t-CyCIF) to generate fluorescence which artifact corrected using the BaSiC tool, stitched registered ASHLAR algorithm, segmented ilastik software MATLAB. extracted features from these HistoCAT software. The resulting can be...
Despite the accumulation of extensive genomic alterations, many cancers fail to be recognized as "foreign" and escape destruction by host immune system. Immunotherapies designed address this problem directly stimulating effector cells have led some remarkable clinical outcomes, but unfortunately, most respond, prompting need identify additional immunomodulatory treatment options.Experimental Design: We elucidated effect a novel paradigm using sustained, low-dose HSP90 inhibition in vitro...
Metachromatic leukodystrophy (MLD) is an autosomal recessive neurodegenerative disorder caused by mutations in the arylsulfatase A (ARSA) gene, resulting lower sulfatase activity and toxic accumulation of sulfatides central peripheral nervous system. Children account for 70% cases become progressively disabled with death occurring within 10 years disease onset. Gene therapy approaches to restore ARSA expression via adeno-associated viral vectors (AAV) have been promising but hampered limited...
Single-cell RNA sequencing (scRNA-seq) experiments provide opportunities to peer into complex tissues at single-cell resolution. However, insightful biological interpretation of scRNA-seq data relies upon precise identification cell types. The ability identify the origin a quickly and accurately will greatly improve downstream analyses. We present Sargent, transformation-free, cluster-free, annotation algorithm for rapidly identifying types based on type-specific markers. demonstrate...
IL-4 and IL-13 have non-redundant effects in olfaction, with loss of smell mice evoked only by intranasal administration IL-4, but not IL-13. IL-4-evoked pathophysiological on olfaction is independent compromised structural integrity the olfactory neuroepithelium. IL-4-IL-4Rα signaling modulates neuronal crosstalk immune cells, suggesting a functional link between impairment neuroinflammation. Abbreviations: IL, interleukin; KO, knock-out; wk, week; WT, wild-type.
Inspection of tissues using a light microscope is the primary method diagnosing many diseases, notably cancer. Highly multiplexed tissue imaging builds on this foundation, enabling collection up to 60 channels molecular information plus cell and morphology antibody staining. This provides unique insight into disease biology promises help with design patient-specific therapies. However, substantial gap remains respect visualizing resulting multivariate image data effectively supporting...
New highly-multiplexed imaging technologies have enabled the study of tissues in unprecedented detail. These methods are increasingly being applied to understand how cancer cells and immune response change during tumor development, progression, metastasis, as well following treatment. Yet, existing analysis approaches focus on investigating small tissue samples a per-cell ba- sis, not taking into account spatial proximity cells, which indicates cell-cell interaction specific biological...
Abstract The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These confer that remains estrogen receptor (ER) dependent. We hypothesized presence ER mutations, continued blockade with therapies target mutant is essential for tumor suppression even chemotherapy treatment. Here, we conducted comprehensive pre-clinical vitro and vivo experiments testing efficacy...
Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of cellular responses to perturbations such as therapeutic interventions and vaccines. Gene relevance is often assessed through differential expression analysis (DEA), which offers a one-dimensional view the transcriptomic landscape. This method potentially overlooks genes with modest changes but profound downstream effects susceptible false positives. We present GENIX (gene network importance examination),...
Single-cell RNA sequencing (scRNA-seq) has revolutionized the study of gene expression at individual cell level, unraveling unprecedented insights into cellular heterogeneity. However, analysis scRNA-seq data remains a challenging and time-consuming task, often demanding advanced computational expertise, rendering it impractical for high-volume environments applications. We present CellBridge, an automated workflow designed to simplify standard procedures entailed in analysis, eliminating...
Abstract Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that causes motor neuron loss in the brain and spinal cord. Neuroinflammation driven by activated microglia astrocytes prominent ALS, but an understanding of cell state dynamics which pathways contribute to remains unclear. Single nucleus RNA sequencing ALS cords demonstrated striking changes glial states, including increased expression inflammatory activation markers. Many these signals converged on...
Response to targeted therapy varies between patients for largely unknown reasons. Here, we developed and applied an integrative platform using mass spectrometry imaging (MSI), phosphoproteomics, multiplexed tissue mapping drug distribution, target engagement, adaptive response gain insights into heterogeneous therapy.Patient-derived xenograft (PDX) lines of glioblastoma were treated with adavosertib, a Wee1 inhibitor, distribution was measured MALDI-MSI. Phosphoproteomics in the same tumors...