A5009301447- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- AI in cancer detection
- Immune cells in cancer
- Cancer Genomics and Diagnostics
- COVID-19 Clinical Research Studies
- Radiomics and Machine Learning in Medical Imaging
- Lung Cancer Research Studies
- Virus-based gene therapy research
- Molecular Biology Techniques and Applications
- CAR-T cell therapy research
- HIV Research and Treatment
- Digital Imaging for Blood Diseases
- Cytomegalovirus and herpesvirus research
- Epigenetics and DNA Methylation
- Advanced biosensing and bioanalysis techniques
- Integrated Circuits and Semiconductor Failure Analysis
- Extracellular vesicles in disease
- SARS-CoV-2 and COVID-19 Research
- Health, Environment, Cognitive Aging
- Gut microbiota and health
- Ion-surface interactions and analysis
- Pancreatic function and diabetes
- Sparse and Compressive Sensing Techniques
- Nanopore and Nanochannel Transport Studies
Broad Institute
2024-2025
Ragon Institute of MGH, MIT and Harvard
2024-2025
Stanford University
2018-2024
University of Pittsburgh Medical Center
2024
Massachusetts Institute of Technology
2024
Stanford Medicine
2023
University of Pittsburgh
2021-2022
Baxter (United States)
2019
New York State College of Agriculture & Life Sciences
2016-2018
Cornell University
2016-2018
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...
Abstract The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health 1 . intesting has length of over nine metres, along which there are differences structure function 2 localization individual cell types, type development trajectories detailed transcriptional programs probably drive these function. Here, to better understand differences, we evaluated...
Highly multiplexed protein imaging is emerging as a potent technique for analyzing distribution within cells and tissues in their native context. However, existing cell annotation methods utilizing high-plex spatial proteomics data are resource intensive necessitate iterative expert input, thereby constraining scalability practicality extensive datasets. We introduce MAPS (Machine learning Analysis of Proteomics Spatial biology), machine approach facilitating rapid precise type...
The intricate interactions between the host immune system and its microbiome constituents undergo dynamic shifts in response to perturbations intestinal tissue environment. Our ability study these events on systems level is significantly limited by situ approaches capable of generating simultaneous insights from both microbial communities. Here, we introduce Microbiome Cartography (MicroCart), a framework for probing across multiple spatial modalities. We demonstrate MicroCart investigating...
Understanding the mechanisms of HIV tissue persistence necessitates ability to visualize microenvironments where infected cells reside; however, technological barriers limit our dissect cellular components these reservoirs. Here, we developed protein and nucleic acid in situ imaging (PANINI) simultaneously quantify DNA, RNA, levels within compartments. By coupling PANINI with multiplexed ion beam (MIBI), measured over 30 parameters across archival lymphoid tissues from healthy or simian...
Abstract Although single-cell and spatial sequencing methods enable simultaneous measurement of more than one biological modality, no technology can capture all modalities within the same cell. For current data integration methods, feasibility cross-modal relies on existence highly correlated, a priori ‘linked’ features. We describe matching X-modality via fuzzy smoothed embedding (MaxFuse), method that, through iterative coembedding, smoothing cell matching, uses information in each...
Abstract The ability to align individual cellular information from multiple experimental sources is fundamental for a systems-level understanding of biological processes. However, currently available tools are mainly designed single-cell transcriptomics matching and integration, generally rely on large number shared features across datasets cell matching. This approach underperforms when applied proteomic due the limited parameters simultaneously accessed lack markers these experiments....
SUMMARY Neuroblastoma is a pediatric cancer arising from the developing sympathoadrenal lineage with complex inter- and intra-tumoral heterogeneity. To chart this complexity, we generated comprehensive cell atlas of 55 neuroblastoma patient tumors, collected two institutions, spanning range clinical, genetic, histologic features. Our combines single-cell/nucleus RNA-seq (sc/scRNA-seq), bulk RNA-seq, whole exome sequencing, DNA methylation profiling, spatial transcriptomics, proteomic...
Abstract The toxic metalloid arsenic has been environmentally ubiquitous since life first arose nearly four billion years ago and presents a challenge for the survival of all living organisms. Its bioavailability varied dramatically over history on Earth. As spread, biogeochemical climate changes cyclically increased decreased bioavailable arsenic. To elucidate adaptation across tree life, we reconstructed phylogeny arsM gene that encodes As(III) S-adenosylmethionine (SAM) methyltransferase....
Abstract Simultaneous visualization of the relationship between multiple biomolecules and their ligands or small molecules at nanometer scale in cells will enable greater understanding how biological processes operate. We present here high-definition multiplex ion beam imaging (HD-MIBI), a secondary mass spectrometry approach capable high-parameter 3D targeted entities exogenously added structurally-unmodified molecules. With this technology, atomic constituents themselves can be used our...
Multiplex imaging technologies are now routinely capable of measuring more than 40 antibody-labeled parameters in single cells. However, lateral spillage signals densely packed tissues presents an obstacle to the assignment high-dimensional spatial features individual cells for accurate cell-type annotation. We devised a method correct cell surface markers between adjacent termed REinforcement Dynamic Spillover EliminAtion (REDSEA). The use REDSEA decreased contaminating from neighboring It...
Intratumoral heterogeneity is a seminal feature of human tumors contributing to tumor progression and response treatment. Current technologies are still largely unsuitable accurately track phenotypes clonal evolution within tumors, especially in genetic manipulations. Here, we developed epitopes for imaging using combinatorial tagging (EpicTags), which coupled multiplexed ion beam (EpicMIBI) situ tracking barcodes tissue microenvironments. Using EpicMIBI, dissected the spatial component cell...
Cellular organization and functions encompass multiple scales in vivo. Emerging high-plex imaging technologies are limited resolving subcellular biomolecular features. Expansion Microscopy (ExM) related techniques physically expand samples for enhanced spatial resolution, but challenging to be combined with enable integrative multiscaled tissue biology insights. Here, we introduce Expand comPRESS hydrOgels (ExPRESSO), an ExM framework that allows protein staining, physical expansion, removal...
Antigen-specific T cells traffic to, are influenced by, and create unique cellular microenvironments. Here we characterize these microenvironments over time with multiplexed imaging in a melanoma model of adoptive cell therapy human patients treated checkpoint inhibitor therapy. Multicellular neighborhood analysis reveals dynamic immune infiltration inflamed tumor neighborhoods associated CD8
The spatial organization of cells in tissues underlies biological function, and recent advances profiling technologies have enhanced our ability to analyze such arrangements study processes disease progression. We propose MESA (multiomics ecological analysis), a framework drawing inspiration from concepts delineate functional shifts across tissue states. introduces metrics systematically quantify diversity identify hot spots, linking patterns phenotypic outcomes, including Furthermore,...
Understanding viral tropism is an essential step toward reducing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, decreasing mortality from disease 2019 (COVID-19) and limiting opportunities for mutant strains to arise. Currently, little known about the extent which distinct tissue sites in human head neck region proximal tract selectively permit SARS-CoV-2 infection replication. In this translational study, we discover key variabilities expression of...
The intricate and dynamic interactions between the host immune system its microbiome constituents undergo shifts in response to perturbations intestinal tissue environment. Our ability study these events on systems level is significantly limited by
single-cell sequencing methods have enabled the profiling of multiple types molecular readouts at cellular resolution, and recent developments in spatial barcoding, situ hybridization, allow such to retain their context. Since no technology can provide complete characterization across all layers biological modalities within same cell, there is pervasive need for computational cross-modal integration (also called diagonal integration) omics data. For current methods, feasibility relies on...