A5001076999- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Protein purification and stability
- Nanofabrication and Lithography Techniques
- Advanced Biosensing Techniques and Applications
- SARS-CoV-2 and COVID-19 Research
- Advanced biosensing and bioanalysis techniques
- Transgenic Plants and Applications
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- HIV Research and Treatment
- Molecular Junctions and Nanostructures
- Cardiac Arrhythmias and Treatments
- Cancer Immunotherapy and Biomarkers
- Glioma Diagnosis and Treatment
- BRCA gene mutations in cancer
- 3D Printing in Biomedical Research
- vaccines and immunoinformatics approaches
- Genetic factors in colorectal cancer
- Food Allergy and Anaphylaxis Research
Massachusetts Institute of Technology
2015-2024
Ragon Institute of MGH, MIT and Harvard
2014-2024
Broad Institute
2015-2024
Allen Institute
2013-2024
Koch Institute for Integrative Cancer Research At MIT
2013-2024
IIT@MIT
2018-2024
Brigham and Women's Hospital
2003-2024
Circadian (United States)
2024
Hadassah Medical Center
2023
University of Maryland, College Park
2023
Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies content in 0.1× coverage whole-genome data without prior knowledge mutations. We apply ichorCNA to 1439 samples 520 patients with metastatic prostate or breast cancers. In earliest tested sample for each patient, 34% have ≥10% tumor-derived cfDNA, sufficient...
Background— Some current pacing systems can automatically detect and record atrial tachyarrhythmias that may be asymptomatic. We prospectively studied a 312-patient (pt) subgroup of MOST (MOde Selection Trial), 2010-patient, 6-year randomized trial DDDR versus VVIR in sinus node dysfunction (SND). The purpose the study was to correlate high rate events (AHREs) detected by pacemaker diagnostics with clinical outcomes. Methods Results— Pacemakers were programmed log an AHRE when >220 bpm...
Composite stamps composed of two layersa stiff layer supported by a flexible layerextend the capabilities soft lithography to generation 50−100-nm features. The preparation these was adapted from procedure originally developed Schmid et al. (Macromolecules 2000, 33, 3042) for microcontact printing. This paper demonstrates how pattern transfer using other lithographic techniquesmicromolding in capillaries, microtransfer molding, and phase-shifting lithographycan be improved two-layer relative...
Recently, there have been significant advances in the fabrication and demonstration of individual molecular electronic wires diode switches. This paper reviews those developments shows how demonstrated devices might be combined to design molecular-scale digital computer logic. The for rectifying switches is refined made more compatible with through introduction intramolecular dopant groups chemically bonded modified wires. Quantum mechanical calculations are performed characterize some...
The release of cytokines by T cells defines a significant part their functional activity in vivo, and ability to produce multiple has been associated with beneficial immune responses. To date, time-integrated end-point measurements have obscured whether these polyfunctional states arise from the simultaneous or successive cytokines. Here, we used serial, time-dependent, single-cell analysis primary human resolve temporal dynamics cytokine secretion individual after activation ex vivo. We...
CCR6 + myelin-reactive T cells from patients with multiple sclerosis secrete inflammatory cytokines compared to healthy subjects, showing a distinct pathogenic gene expression profile and sharing transcriptome homology encephalitogenic CD4 isolated mice experimental autoimmune encephalitis.
Genome-wide association studies (GWAS) have identified genetic variants associated with age-related macular degeneration (AMD), one of the leading causes blindness in elderly. However, it has been challenging to identify cell types AMD given complexity disease. Here we perform massively parallel single-cell RNA sequencing (scRNA-seq) human retinas using two independent platforms, and report first transcriptomic atlas retina. Using a multi-resolution network-based analysis, all major retinal...
Abstract Glioblastomas (GBM) with EGFR amplification represent approximately 50% of newly diagnosed cases, and recent studies have revealed frequent coexistence multiple aberrations within the same tumor, which has implications for mutation cooperation treatment resistance. However, bulk tumor sequencing cannot resolve patterns how coexist other mutations single cells. Here, we applied a population-based single-cell whole-genome methodology to characterize genomic heterogeneity in...
Intracerebral hemorrhage (ICH) is a devastating form of stroke that results from the rupture blood vessel in brain, leading to mass within brain parenchyma. The injury causes rapid inflammatory reaction includes activation tissue-resident microglia and recruitment blood-derived macrophages other leukocytes. In this work, we investigated specific responses following ICH with aim identifying pathways may aid recovery after injury. We used longitudinal transcriptional profiling murine model...
High-throughput single-cell RNA-sequencing (scRNA-seq) methodologies enable characterization of complex biological samples by increasing the number cells that can be profiled contemporaneously. Nevertheless, these approaches recover less information per cell than low-throughput strategies. To accurately report expression key phenotypic features cells, scRNA-seq platforms are needed both high fidelity and throughput. address this need, we created Seq-Well S3 ("Second-Strand Synthesis"), a...
Immunotherapies targeting the immune checkpoint receptor programmed cell death protein 1 (PD-1) have shown remarkable efficacy in treating cancer. CD4+CD25hiFoxP3+ Tregs are critical regulators of responses autoimmunity and malignancies, but functional status human expressing PD-1 remains unclear. We examined molecular features PD-1hi healthy subjects patients with glioblastoma multiforme (GBM), combining assays, RNA sequencing, cytometry by time flight (CyTOF). In both GBM subjects,...
Purpose Cell-free DNA (cfDNA) offers the potential for minimally invasive genome-wide profiling of tumor alterations without biopsy and may be associated with patient prognosis. Triple-negative breast cancer (TNBC) is characterized by few mutations but extensive somatic copy number (SCNAs), yet little known regarding SCNAs in metastatic TNBC. We sought to evaluate TNBC exclusively via cfDNA determine if fraction overall survival Patients Methods In this retrospective cohort study, we...
Mycobacterium tuberculosis lung infection results in a complex multicellular structure: the granuloma. In some granulomas, immune activity promotes bacterial clearance, but others, bacteria persist and grow. We identified correlates of control cynomolgus macaque granulomas by co-registering longitudinal positron emission tomography computed imaging, single-cell RNA sequencing, measures clearance. Bacterial persistence occurred enriched for mast, endothelial, fibroblast, plasma cells,...
Liquid biopsies including circulating tumor cells (CTCs) and cell-free DNA (cfDNA) have enabled minimally invasive characterization of many cancers, but are rarely analyzed together. Understanding the detectability genomic concordance CTCs cfDNA may inform their use in guiding cancer precision medicine. Here, we report blood samples from 107 56 patients with multiple myeloma (MM), respectively. Using ultra-low pass whole-genome sequencing, find both fractions correlate disease progression....
Abstract Purpose: Existing cell-free DNA (cfDNA) methods lack the sensitivity needed for detecting minimal residual disease (MRD) following therapy. We developed a test tracking hundreds of patient-specific mutations to detect MRD with 1,000-fold lower error rate than conventional sequencing. Experimental Design: compared our approach digital droplet PCR (ddPCR) in dilution series, then retrospectively identified two cohorts patients who had undergone prospective plasma sampling and clinical...
Chimeric antigen receptor (CAR) T cell therapy effectively treats human cancer, but the loss of recognized by CAR poses a major obstacle. We found that in vivo vaccine boosting cells triggers engagement endogenous immune system to circumvent antigen-negative tumor escape. Vaccine-boosted promoted dendritic (DC) recruitment tumors, increased uptake DCs, and elicited priming anti-tumor cells. This process was accompanied shifts metabolism toward oxidative phosphorylation (OXPHOS) critically...