Leonardo A. Sepúlveda

ORCID: 0000-0003-3602-1009
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About
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Research Areas
  • 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

10.1038/s43018-020-0026-6 article EN Nature Cancer 2020-02-17

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...

10.1038/s43018-021-00301-w article EN cc-by Nature Cancer 2021-12-24

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...

10.1126/science.aad0635 article EN Science 2016-03-10

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,...

10.1038/msb.2010.96 article EN cc-by-nc-nd Molecular Systems Biology 2010-01-01
Dimitra Georgopoulou Maurizio Callari Oscar M. Rueda Abigail Shea Alistair Martin and 95 more Agnese Giovannetti Fatime Qosaj A. Dariush Suet‐Feung Chin Larissa S. Carnevalli Elena Provenzano Wendy Greenwood Giulia Lerda Elham Esmaeilishirazifard Martin O’Reilly Violeta Serra Dario Bressan H. Raza Ali M. Al Sa’d Shahar Alon Samuel Aparício Giorgia Battistoni Shankar Balasubramanian Robert O. Becker Bernd Bodenmiller E. S. Boyden Dario Bressan Alejandra Bruna Marcel Burger Carlos Caldas Maurizio Callari Ian G. Cannell Helen Casbolt N. Chornay Yi Cui A. Dariush K. Dinh A. Emenari Y. Eyal-Lubling Jean Fan Ali Fatemi Edward A. Fisher E. A. González-Solares C. Gónzalez-Fernández Douglas C. Goodwin Wendy Greenwood Francesco Grimaldi Gregory J. Hannon Owen Harris Shelley Harris Cristina Jauset Johanna A. Joyce Emmanouil D. Karagiannis Tatjana Kovačević Laura Kuett Russell Kunes Yoldaş A. Küpcü Daniel Lai Emma Laks Hsuan Lee M. Lee Giulia Lerda Y. Li Andrew McPherson Neal L. Millar Claire M. Mulvey Fiona Nugent Ciara H. O’Flanagan Marta Pàez‐Ribes I. Pearsall Fatime Qosaj Andrew Roth Oscar M. Rueda Tamara Ruiz Kirsty Sawicka Leonardo A. Sepúlveda Sohrab P. Shah Abigail Shea Anubhav Sinha Adrian L. Smith S. Tavaré Sandra Tietscher Ignacio Vázquez-Garćıa Siegfried Vogl N. A. Walton Asmamaw T. Wassie Spencer S. Watson Joanna Weselak Sonja Wild Elena Williams Jonas Windhager Tristan Whitmarsh C. Xia Ping Zheng Xiaowei Zhuang Gordon B. Mills H. Raza Ali Sabina S. Cosulich Gregory J. Hannon Alejandra Bruna

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...

10.1038/s41467-021-22303-z article EN cc-by Nature Communications 2021-03-31
Dario Bressan N. A. Walton Gregory J. Hannon Mohammad Al Sa’d Bruno Albuquerque and 95 more H. Raza Ali Martina Alini Samuel Aparício Heather Ashmore Thomas J. Ashmore Vinci Au Shankar Balasubramanian Caroline Baril Giorgia Battistoni Sean Beatty Robby Becker Bernd Bodenmiller Alina Bollhagen Carla Boquetale Edward S. Boyden Dario Bressan Alejandra Bruna Marcel Burger Carlos Caldas Maurizio Callari Ian G. Cannell Hannah Casbolt Nick Chornay Nikki Coutts A. Dariush Lauren Deighton Khanh N. Dinh Natalie Duncan Yaniv Eyal-Lubling Ilaria Falciatori Jean Fan Atefeh Fatemi Debarati Ghosh Carlos González‐Fernández E. A. González-Solares Wendy Greenwood Flaminia Grimaldi Gregory J. Hannon Owen Harris Suvi Harris Nicole Hemmer Kui Hua Muhammad Irfan Cristina Jauset Johanna A. Joyce Tatjana Kovačević Laura Kuett Russell Kunes A. Yoldaş Daniel Lai Emma Laks Hsuan Lee Max Lee Giulia Lerda Yangguang Li J. Lovell Yangning Lu John C. Marioni Andrew McPherson Neil S. Millar Alireza Molaeinezhad Claire M. Mulvey Natasha Narayanan João C. F. Nogueira Fiona Nugent Ciara H. O’Flanagan Marta Ribes Isabella Pearsall Sarah M. Pearsall Brett Pryor Fatime Qosaj Clare A. Rebbeck Andrew Roth Oscar M. Rueda Teresa Ruíz Kirsty Sawicka Leonardo A. Sepúlveda Sohrab P. Shah Abigail Shea Anubhav Sinha Austin Smith Leigh M. Smith Simon Tavaré Ignacio Vázquez-Garćıa Sara Lisa Vogl N. A. Walton Spencer S. Watson Joanna Weselak Tristan Whitmarsh Sophia A. Wild Elena Williams Jonas Windhager Chenglong Xia Chee Ying Sia Chi Zhang

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...

10.1158/2159-8290.cd-24-1686 article EN Cancer Discovery 2025-01-13
Dario Bressan N. A. Walton Gregory J. Hannon Mohammad Al Sa’d Bruno Albuquerque and 95 more H. Raza Ali Martina Alini Samuel Aparício Heather Ashmore Thomas J. Ashmore Vinci Au Shankar Balasubramanian Caroline Baril Giorgia Battistoni Sean Beatty Robby Becker Bernd Bodenmiller Alina Bollhagen Carla Boquetale Edward S. Boyden Dario Bressan Alejandra Bruna Marcel Burger Carlos Caldas Maurizio Callari Ian G. Cannell Hannah Casbolt Nick Chornay Nikki Coutts A. Dariush Lauren Deighton Khanh N. Dinh Natalie Duncan Yaniv Eyal-Lubling Ilaria Falciatori Jean Fan Atefeh Fatemi Debarati Ghosh Carlos González‐Fernández E. A. González-Solares Wendy Greenwood Flaminia Grimaldi Gregory J. Hannon Owen Harris Suvi Harris Nicole Hemmer Kui Hua Muhammad Irfan Cristina Jauset Johanna A. Joyce Tatjana Kovačević Laura Kuett Russell Kunes A. Yoldaş Daniel Lai Emma Laks Hsuan Lee Max Lee Giulia Lerda Yangguang Li J. Lovell Yangning Lu John C. Marioni Andrew McPherson Neil S. Millar Alireza Molaeinezhad Claire M. Mulvey Natasha Narayanan João C. F. Nogueira Fiona Nugent Ciara H. O’Flanagan Marta Ribes Isabella Pearsall Sarah M. Pearsall Brett Pryor Fatime Qosaj Clare A. Rebbeck Andrew Roth Oscar M. Rueda Teresa Ruíz Kirsty Sawicka Leonardo A. Sepúlveda Sohrab P. Shah Abigail Shea Anubhav Sinha Austin Smith Leigh M. Smith Simon Tavaré Ignacio Vázquez-Garćıa Sara Lisa Vogl N. A. Walton Spencer S. Watson Joanna Weselak Tristan Whitmarsh Sophia A. Wild Elena Williams Jonas Windhager Chenglong Xia Chee Ying Sia Chi Zhang

<p>IMAXT Consortium Author List</p>

10.1158/2159-8290.28193715 preprint EN cc-by 2025-01-13
Dario Bressan N. A. Walton Gregory J. Hannon Mohammad Al Sa’d Bruno Albuquerque and 95 more H. Raza Ali Martina Alini Samuel Aparício Heather Ashmore Thomas J. Ashmore Vinci Au Shankar Balasubramanian Caroline Baril Giorgia Battistoni Sean Beatty Robby Becker Bernd Bodenmiller Alina Bollhagen Carla Boquetale Edward S. Boyden Dario Bressan Alejandra Bruna Marcel Burger Carlos Caldas Maurizio Callari Ian G. Cannell Hannah Casbolt Nick Chornay Nikki Coutts A. Dariush Lauren Deighton Khanh N. Dinh Natalie Duncan Yaniv Eyal-Lubling Ilaria Falciatori Jean Fan Atefeh Fatemi Debarati Ghosh Carlos González‐Fernández E. A. González-Solares Wendy Greenwood Flaminia Grimaldi Gregory J. Hannon Owen Harris Suvi Harris Nicole Hemmer Kui Hua Muhammad Irfan Cristina Jauset Johanna A. Joyce Tatjana Kovačević Laura Kuett Russell Kunes A. Yoldaş Daniel Lai Emma Laks Hsuan Lee Max Lee Giulia Lerda Yangguang Li J. Lovell Yangning Lu John C. Marioni Andrew McPherson Neil S. Millar Alireza Molaeinezhad Claire M. Mulvey Natasha Narayanan João C. F. Nogueira Fiona Nugent Ciara H. O’Flanagan Marta Ribes Isabella Pearsall Sarah M. Pearsall Brett Pryor Fatime Qosaj Clare A. Rebbeck Andrew Roth Oscar M. Rueda Teresa Ruíz Kirsty Sawicka Leonardo A. Sepúlveda Sohrab P. Shah Abigail Shea Anubhav Sinha Austin Smith Leigh M. Smith Simon Tavaré Ignacio Vázquez-Garćıa Sara Lisa Vogl N. A. Walton Spencer S. Watson Joanna Weselak Tristan Whitmarsh Sophia A. Wild Elena Williams Jonas Windhager Chenglong Xia Chee Ying Sia Chi Zhang

<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...

10.1158/2159-8290.c.7623345 preprint EN 2025-01-13
Dario Bressan N. A. Walton Gregory J. Hannon Mohammad Al Sa’d Bruno Albuquerque and 95 more H. Raza Ali Martina Alini Samuel Aparício Heather Ashmore Thomas J. Ashmore Vinci Au Shankar Balasubramanian Caroline Baril Giorgia Battistoni Sean Beatty Robby Becker Bernd Bodenmiller Alina Bollhagen Carla Boquetale Edward S. Boyden Dario Bressan Alejandra Bruna Marcel Burger Carlos Caldas Maurizio Callari Ian G. Cannell Hannah Casbolt Nick Chornay Nikki Coutts A. Dariush Lauren Deighton Khanh N. Dinh Natalie Duncan Yaniv Eyal-Lubling Ilaria Falciatori Jean Fan Atefeh Fatemi Debarati Ghosh Carlos González‐Fernández E. A. González-Solares Wendy Greenwood Flaminia Grimaldi Gregory J. Hannon Owen Harris Suvi Harris Nicole Hemmer Kui Hua Muhammad Irfan Cristina Jauset Johanna A. Joyce Tatjana Kovačević Laura Kuett Russell Kunes A. Yoldaş Daniel Lai Emma Laks Hsuan Lee Max Lee Giulia Lerda Yangguang Li J. Lovell Yangning Lu John C. Marioni Andrew McPherson Neil S. Millar Alireza Molaeinezhad Claire M. Mulvey Natasha Narayanan João C. F. Nogueira Fiona Nugent Ciara H. O’Flanagan Marta Ribes Isabella Pearsall Sarah M. Pearsall Brett Pryor Fatime Qosaj Clare A. Rebbeck Andrew Roth Oscar M. Rueda Teresa Ruíz Kirsty Sawicka Leonardo A. Sepúlveda Sohrab P. Shah Abigail Shea Anubhav Sinha Austin Smith Leigh M. Smith Simon Tavaré Ignacio Vázquez-Garćıa Sara Lisa Vogl N. A. Walton Spencer S. Watson Joanna Weselak Tristan Whitmarsh Sophia A. Wild Elena Williams Jonas Windhager Chenglong Xia Chee Ying Sia Chi Zhang

<p>IMAXT Consortium Author List</p>

10.1158/2159-8290.28228999 preprint EN cc-by 2025-01-17

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...

10.1109/ipdps.2009.5160930 article EN 2009-05-01

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...

10.1371/journal.pgen.1003901 article EN cc-by PLoS Genetics 2013-11-07
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