About

Our research group combines genomics and computational biology to study the biology of aging and age-associated diseases

Research topics

• Biology
• Genetics
• Cell biology
• Medicine
• Immunology
• Computational biology
• Gerontology
• Internal medicine
• Neuroscience

Selected publications

• Comet Protocol for FFPE slides - Benchmarking Project SenNet v1

  2026-04-27

  articleOpen access1st authorCorresponding

  This protocol describes a workflow for highly multiplexed protein measurements using the Comet machine from Lunaphore. This method is optimized for formalin-fixed paraffin-embedded (FFPE) tissue sections and enables repeated cycles of staining, imaging and antibody elution using conventional primary and secondary antibodies. By sequentially eluting antibodies between imaging rounds, this approach allows the detection of a large number of protein targets within the same tissue section while preserving spatial context. This protocol was adapted from methods developed in the laboratory of Dr Joao Passos made for iterative indirect immunofluorescence imaging (4i).

  PublisherOA PDFDOI

• Advancing senescence translation through the Senotherapeutics Biomarker Consortium

  Nature Aging · 2026-03-03

  article
  PublisherDOI

• Geometric Diagrams of Genomes: constructing a visual grammar for 3D genomics

  Genome biology · 2025-06-26 · 1 citations

  articleOpen access

  Advances in the field of three-dimensional (3D) genomics have revealed an ever-expanding array of architectural features that were unknown only a few years ago. Just as ribbon diagrams integrate spatial and symbolic representation to communicate the shape of a protein, the representation of genomes in 3D space requires the development and use of new cartographic symbols and visual conventions. Here, we propose a conceptualized grammar that makes it easier to create visual 3D representations of genomes.

  PublisherOA PDFDOI

• Processed data for: Improved short nascent strand sequencing (iSNS-seq) enhances DNA replication origin detection and reduces non-origin biases

  Zenodo (CERN European Organization for Nuclear Research) · 2025-12-01

  datasetOpen access

  This Zenodo deposition contains normalized coverage tracks (bigWig) and peak calls (narrowPeak) associated with our study investigating and comparing the performance of improved short nascent strand sequencing (SNS-seq) and traditional SNS-seq for DNA replication origin mapping in Saccharomyces cerevisiae. The raw data is deposited separately in the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB95115.

  PublisherDOI

• Cytosolic DNA crosstalk in senescence: a new axis of inflammatory signaling?

  The EMBO Journal · 2025-08-29 · 7 citations

  articleOpen access

  Cellular senescence is a form of stable growth arrest that contributes to aging and age-related diseases, in part through the senescence-associated secretory phenotype (SASP). Recent studies show that senescent cells accumulate several species of cytosolic DNAs, including mitochondrial DNA (mtDNA), cytoplasmic chromatin fragments (CCFs), and retrotransposable element cDNAs, which collectively activate the cGAS–STING pathway and drive SASP expression. Surprisingly, downregulating any one of these DNA species is often enough to suppress the SASP, raising key questions about their functional interactions. We propose that these cytosolic DNA species do not act in isolation but instead either follow a coordinated sequence or engage in synergistic crosstalk to amplify and sustain inflammatory signaling. While therapeutic approaches directly targeting the cGAS–STING pathway are being developed, we argue that blocking the sources of cytosolic DNA might be a more specific and safer strategy to target the deleterious effects of senescent cells. In particular, this approach should enable reducing chronic inflammation without impairing important immune functions, offering a new direction for therapies aimed at promoting healthy aging.

  PublisherOA PDFDOI

• Senescence-Associated Chromatin Rewiring Promotes Inflammation and Transposable Element Activation

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-17 · 3 citations

  preprintOpen accessSenior authorCorresponding

  Cellular senescence is a stable form of cell cycle arrest that contributes to aging and age-associated diseases through the secretion of inflammatory factors collectively known as the senescence-associated secretory phenotype (SASP). While senescence is driven by transcriptional and epigenetic changes, the contribution of higher-order genome organization remains poorly defined. Here, we present the highest-resolution Hi-C maps (~3 kb) to date of proliferating, quiescent, and replicative senescent (RS) human fibroblasts, enabling a comprehensive analysis of 3D genome architecture during senescence. Our analyses reveal widespread senescence-associated remodeling of chromatin architecture, including extensive compartment and subcompartment switching toward transcriptionally active states, and a dramatic increase in unique chromatin loops. These structural features correlate with local DNA hypomethylation and are largely independent of canonical CTCF binding. The altered 3D genome landscape supports expression of SASP genes, inflammation-related pathways, and neuronal gene signatures consistent with age-associated epigenetic drift. We further demonstrate that architectural changes at multiple levels, including compartments, subcompartments, and loops, facilitate the derepression of LINE-1 retrotransposons, linking 3D chromatin structure to activation of proinflammatory transposable elements. Interestingly, quiescent cells, commonly used as senescence controls, exhibited substantial overlap in inflammatory gene expression with senescent cells, raising important considerations for experimental design. Structural analysis of cell cycle genes showed distinct chromatin configurations in senescence versus quiescence, despite similar transcriptional repression. Together, our results establish a high-resolution framework for understanding how genome architecture contributes to the senescent state.

  PublisherOA PDFDOI

• Skin health and biological aging

  Nature Aging · 2025-06-17 · 34 citations

  reviewOpen access
  PublisherOA PDFDOI

• Improved short nascent strand sequencing (iSNS-seq) enhances DNA replication origin detection and reduces non-origin biases

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-24

  articleOpen access

  Abstract Identifying DNA replication origins in human and other metazoan genomes has been challenging, as highlighted by the fact that various methods for mapping them have produced conflicting results. A popular method, short nascent strand sequencing (SNS-seq or NS-seq), enriches newly replicated short single-stranded DNA by size selection and λ exonuclease ( λ -exo) digestion of parental DNA. Surprisingly, SNS-seq has never been validated in Saccharomyces cerevisiae where origins have been well characterized genome-wide. We improved the SNS-seq protocol through biochemical optimization and benchmarked its origin-mapping sensitivity and precision with traditional SNS-seq in asynchronous populations of S. cerevisiae . The improved SNS-seq protocol significantly enhanced the enrichment of origin-derived DNA. S trikingly, the traditional SNS-seq failed to detect known origins and instead enriched non-origin DNA, likely arising from RNA:DNA hybrids. These findings have important implications for the interpretation of previously p ublished datasets that rely on λ -exo for origin mapping. Overall, our biochemical and genomic analyses help unravel the mystery of the inconsistencies between SNS-seq and other techniques used to map DNA replication origins genome-wide.

  PublisherDOI

• Processed data for: Improved short nascent strand sequencing (iSNS-seq) enhances DNA replication origin detection and reduces non-origin biases

  Zenodo (CERN European Organization for Nuclear Research) · 2025-12-01

  datasetOpen access

  This Zenodo deposition contains normalized coverage tracks (bigWig) and peak calls (narrowPeak) associated with our study investigating and comparing the performance of improved short nascent strand sequencing (SNS-seq) and traditional SNS-seq for DNA replication origin mapping in Saccharomyces cerevisiae. The raw data is deposited separately in the European Nucleotide Archive (ENA) at EMBL-EBI under accession number PRJEB95115.

  PublisherDOI

• DISSECTING THE HETEROGENEITY OF SENESCENCE: PROFILING PRIMARY AND SECONDARY SENESCENT STATES USING SINGLE-CELL AND SPATIAL TRANSCRIPTOMICS

  Innovation in Aging · 2024-12-01

  articleOpen access1st authorCorresponding

  Abstract Cellular senescence is a state of irreversible cell cycle arrest, contributing to age-associated tissue function decline due to the accumulation of senescent cells. The Senescence Associated Secretory Phenotype (SASP), a collection of signaling molecules and growth factors secreted by these cells, plays a significant role in the sterile inflammation seen in aging tissues. Recent studies, both in vivo and in vitro, have demonstrated that senescence is a heterogeneous phenotype, varying based on cell type, induction method, and duration of senescence. An important aspect of this heterogeneity is the distinction between primary and secondary senescence; primary senescent cells can induce nearby cells into a secondary senescent state, which shares some markers with primary senescence but differs significantly in others, such as the SASP. In this study, we explore the evolution of primary and secondary senescence over time by profiling individual cells during the early stages of senescence establishment using single-cell transcriptomics. We have developed an AI/ML methodology capable of classifying cells into primary and various forms of secondary senescence. This methodology is compared with existing methods like SenMayo and SenSig, and applied to time-course scRNA-seq data to determine the proportion of cells in different senescent states. Additionally, we present findings on the identification of senescent cells in vivo using spatial transcriptomics to study the aging mouse liver.

  PublisherOA PDFDOI

Recent grants

• BioMedical Big Data Core

  NIH · $45.2M · 2016–2026

• The Role of Somatic Transposition in Age-associated Genomic Instability

  NIH · $2.2M · 2017–2024

• Brown University Training Program in the Molecular Biology of Aging

  NIH · $2.9M · 2012–2027

• NIH Grant R56AG05058201

  NIH · $568k · 2017

• NIH Grant K25AG028753

  NIH · $693k · 2013

Frequent coauthors

• John M. Sedivy

  Brown University

  87 shared

• Nathan Intrator

  79 shared

• Stephen L. Helfand

  Brown University

  65 shared

• Steven W. Criscione

  AstraZeneca (United States)

  63 shared

• Yee Voan Teo

  Brown University

  53 shared

• Shane A. Evans

  Teikoku Pharma (United States)

  48 shared

• Marco De Cecco

  Brown University

  36 shared

• Leon N. Cooper

  University of Sydney

  31 shared