A5051288191- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- CAR-T cell therapy research
- Cancer Genomics and Diagnostics
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer-related gene regulation
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- Gene Regulatory Network Analysis
- Plant Molecular Biology Research
- Genomics and Phylogenetic Studies
- Chromatin Remodeling and Cancer
- Cancer-related molecular mechanisms research
- Cell Image Analysis Techniques
- Fungal Plant Pathogen Control
- 3D Printing in Biomedical Research
- Ubiquitin and proteasome pathways
- Skin Protection and Aging
- Genetic Associations and Epidemiology
Massachusetts Institute of Technology
2009-2024
Ragon Institute of MGH, MIT and Harvard
2023-2024
Broad Institute
2021-2024
Harvard University Press
2024
Stanford University
2015-2023
Allen Institute
2023
Koch Institute for Integrative Cancer Research At MIT
2023
Palo Alto University
2018
Johnson University
1998
To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics multiplexed ion beam imaging from a series human cSCCs matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating epidermal states, tumor-specific keratinocyte (TSK) population unique to cancer, which localized fibrovascular niche. Integration data mapped ligand-receptor networks specific types, revealing...
The engineering of many-component, synthetic biological systems is being made easier by the development collections reusable, standard parts. However, complexity biology makes it difficult to predict extent which such efforts will succeed. As a first practical example, Registry Standard Biological Parts started at MIT now maintains and distributes thousands BioBrick parts are only standardized in terms how individual physically assembled into multi-component systems, most remain...
We have generated a series of variable-strength, constitutive, bacterial promoters that act predictably in different sequence contexts, span two orders magnitude strength and contain convenient sites for cloning the introduction downstream open-reading frames. Importantly, their design insulates these from stimulatory or repressive effects many 5′- 3′-sequence elements. show our library produce constant relative levels proteins multiple genetic contexts. This set should be useful resource...
Open chromatin regions are correlated with active regulatory elements in development and dysregulated diseases. The BAF (SWI/SNF) complex is essential for development, has been demonstrated to remodel reconstituted vitro control the accessibility of a few individual vivo. However, it remains unclear where how controls open landscape regulate developmental processes, such as human epidermal differentiation. Using novel "on-plate" ATAC-sequencing approach profiling landscapes low number...
Somatic progenitors sustain tissue self-renewal while suppressing premature differentiation. Protein arginine methyltransferases (PRMTs) affect many processes; however, their role in progenitor function is incompletely understood. PRMT1 was found to be the most highly expressed PRMT epidermal and downregulated during In targeted mouse knockouts long-term regenerated human mosaic epidermis vivo, loss abolished led Mass spectrometry of protein interactome identified CSNK1a1 kinase, which also...
ABSTRACT We present Omni-ATAC, an improved ATAC-seq protocol for chromatin accessibility profiling that works across multiple applications with substantial improvement of signal-to-background ratio and information content. The Omni-ATAC enables from archival frozen tissue samples 50 μm sections, revealing the activities disease-associated DNA elements in distinct human brain structures. interrogation personal regulomes context translational studies.
Abstract Genome conformation is central to gene control but challenging interrogate. Here we present HiChIP, a protein-centric chromatin method. HiChIP improves the yield of conformation-informative reads by over 10-fold and lowers input requirement 100-fold relative ChIA-PET. cohesin reveals multi-scale genome architecture with greater signal background than in situ Hi-C. Thus, adds toolbox 3D structure regulation for diverse biomedical applications.
Abstract Aortic root aneurysm formation is a cardinal feature of Marfan syndrome (MFS) and likely TGF‐β driven via Smad (canonical) ERK (non‐canonical) signalling. The current study assesses human MFS vascular smooth muscle cell (SMC) phenotype, focusing on individual contributions by ERK, with Notch3 signalling identified as novel compensatory mechanism against TGF‐β‐driven pathology. Although significant activation mixed contractile gene expression patterns were observed traditional...
We present a clinicopathological study and the first molecular genetic analysis of family with 2 siblings affected by rare, protracted form juvenile neuronal ceroid lipofuscinosis (JNCL). Molecular studies showed that both siblings, in addition to being heterozygous for 1.02-kb CLN3 deletion, common mutation JNCL, also had G-to-A missense at nucleotide 1,020 cDNA sequence on non-1.02-kb deletion chromosomes. This point resulted substitution glutamic acid lysine position 295 protein. Thus,...
Abstract Immune cells transduce environmental stimuli into responses essential for host health via complex signaling cascades. T cells, in particular, leverage their unique cell receptors (TCRs) to detect specific Human Leukocyte Antigen (HLA)-presented peptides. TCR activation is then relayed linker of (LAT), a TCR-proximal disordered adapter protein, which organizes protein partners and mediates the propagation signals down diverse pathways including NFAT AP-1. Here, we studied how...
Under chronic stress, cells must balance competing demands between cellular survival and tissue function. In metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD/NASH), hepatocytes cooperate with structural immune to perform crucial metabolic, synthetic, detoxification functions despite nutrient imbalances. While prior work has emphasized stress-induced drivers of cell death, the dynamic adaptations surviving their functional repercussions remain unclear. Namely,...