Leonardo A. Sepúlveda
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Gene Regulatory Network Analysis
- Bacterial Genetics and Biotechnology
- Evolution and Genetic Dynamics
- Cell Image Analysis Techniques
- Health, Environment, Cognitive Aging
- Advanced Fluorescence Microscopy Techniques
- Bioinformatics and Genomic Networks
- CRISPR and Genetic Engineering
- Delphi Technique in Research
- Bacteriophages and microbial interactions
- Cancer Cells and Metastasis
- Protein Structure and Dynamics
- DNA Repair Mechanisms
- Developmental Biology and Gene Regulation
- Breast Cancer Treatment Studies
- Molecular Biology Techniques and Applications
- Viral Infections and Outbreaks Research
- RNA and protein synthesis mechanisms
- Cellular Mechanics and Interactions
- DNA and Nucleic Acid Chemistry
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Immunotherapy and Immune Responses
Howard Hughes Medical Institute
2020-2022
Harvard University
2020-2022
Engineering Arts (United States)
2021
Baylor College of Medicine
2010-2017
Center for Theoretical Biological Physics
2016
Rice University
2016
University of Illinois Urbana-Champaign
2009-2013
Abstract A holistic understanding of tissue and organ structure function requires the detection molecular constituents in their original three-dimensional (3D) context. Imaging mass cytometry (IMC) enables simultaneous up to 40 antigens transcripts using metal-tagged antibodies but has so far been restricted two-dimensional imaging. Here we report development 3D IMC for multiplexed analysis at single-cell resolution demonstrate utility technology by human breast cancer samples. The resulting...
In vivo mapping of transcription-factor binding to the transcriptional output regulated gene is hindered by probabilistic promoter occupancy, presence multiple copies, and cell-to-cell variability. We demonstrate how overcome these obstacles in lysogeny maintenance bacteriophage lambda, P(RM). simultaneously measured concentration lambda repressor CI number messenger RNAs (mRNAs) from P(RM) individual Escherichia coli cells, used a theoretical model identify stochastic activity corresponding...
The ability of living cells to maintain an inheritable memory their gene‐expression state is key cellular differentiation. Bacterial lysogeny serves as a simple paradigm for long‐term memory. In this study, we address the following question: in absence external perturbation, how long will cell stay lysogenic before spontaneously switching away from that state? We show by direct measurement lysogen stability exhibits exponential dependence on frequency activity bursts fate‐determining gene,...
The heterogeneity of breast cancer plays a major role in drug response and resistance has been extensively characterized at the genomic level. Here, single-cell mass cytometry (BCMC) panel is optimized to identify cell phenotypes their oncogenic signalling states biobank patient-derived tumour xenograft (PDTX) models representing diversity human cancer. BCMC identifies 13 cellular (11 2 murine), associated with both subtypes specific features. Pre-treatment phenotypic composition determinant...
Summary: The Imaging and Molecular Annotation of Xenografts Tumors Cancer Grand Challenges team was set up with the objective developing “next generation” pathology cancer research by using a combination single-cell spatial omics tools to produce 3D molecularly annotated maps tumors. Its activities overlapped, in some cases catalyzed, revolution biology that saw new technologies being deployed investigate roles tumor heterogeneity micro-environment. See related article Stratton et al., p. 22...
<p>IMAXT Consortium Author List</p>
<div>Summary:<p>The Imaging and Molecular Annotation of Xenografts Tumors Cancer Grand Challenges team was set up with the objective developing “next generation” pathology cancer research by using a combination single-cell spatial omics tools to produce 3D molecularly annotated maps tumors. Its activities overlapped, in some cases catalyzed, revolution biology that saw new technologies being deployed investigate roles tumor heterogeneity micro-environment.</p><p><a...
<p>IMAXT Consortium Author List</p>
To address the problem of performing long time simulations biochemical pathways under in vivo cellular conditions, we have developed a lattice-based, reaction-diffusion model that uses graphics processing unit (GPU) as computational co-processor. The method has been specifically designed from beginning to take advantage GPU's capacity perform massively parallel calculations by not only executing core set mathematical calculations, but also running much underlying algorithmic logic on GPU. In...
Robustness is a property built into biological systems to ensure stereotypical outcomes despite fluctuating inputs from gene dosage, biochemical noise, and the environment. During development, robustness safeguards embryos against structural functional defects. Yet, our understanding of how achieved in limited. While much attention has been paid role signaling networks promoting robust cell fate determination, little done rigorously assay mechanical processes like morphogenesis are designed...