About

Joseph R. Ecker, PhD, is a professor at the Salk Institute for Biological Studies and the Director of the Genomic Analysis Laboratory. His research focuses on understanding the epigenome, which involves chemical modifications to DNA that influence gene expression. Ecker became interested in the epigenome while studying Arabidopsis thaliana, a model plant, and developed the MethylC-Seq method to map epigenetic tags in various organisms. His work has significantly advanced the understanding of epigenetic regulation, including the first mapping of the human epigenome and insights into its variability and role in disease. Ecker's research extends to the human brain, where he has demonstrated the dynamic nature of the epigenome during development and is investigating its implications for disorders such as schizophrenia and Alzheimer’s disease. His contributions also include sequencing the first plant genome, creating a comprehensive database of gene mutations, and identifying genes involved in plant responses to hormones. Ecker has received numerous awards and honors, including election to the National Academy of Sciences and the American Academy of Arts and Sciences, and is an investigator at the Howard Hughes Medical Institute.

Research topics

• Biology
• Genetics
• Computational biology
• Neuroscience
• Evolutionary biology
• Computer Science
• Botany
• Cell biology
• Environmental health
• Cartography
• Anatomy
• Geography
• Medicine
• Biochemistry

Selected publications

• Leaf cell-specific and single-cell transcriptional profiling reveals a role for the palisade layer in UV light protection

  The Plant Cell · 2022 · 96 citations

  • Biology
  • Botany
  • Cell biology

  Like other complex multicellular organisms, plants are composed of different cell types with specialized shapes and functions. For example, most laminar leaves consist of multiple photosynthetic cell types. These cell types include the palisade mesophyll, which typically forms one or more cell layers on the adaxial side of the leaf. Despite their importance for photosynthesis, we know little about how palisade cells differ at the molecular level from other photosynthetic cell types. To this end, we have used a combination of cell-specific profiling using fluorescence-activated cell sorting and single-cell RNA-sequencing methods to generate a transcriptional blueprint of the palisade mesophyll in Arabidopsis thaliana leaves. We find that despite their unique morphology, palisade cells are otherwise transcriptionally similar to other photosynthetic cell types. Nevertheless, we show that some genes in the phenylpropanoid biosynthesis pathway have both palisade-enriched expression and are light-regulated. Phenylpropanoid gene activity in the palisade was required for production of the ultraviolet (UV)-B protectant sinapoylmalate, which may protect the palisade and/or other leaf cells against damaging UV light. These findings improve our understanding of how different photosynthetic cell types in the leaf can function uniquely to optimize leaf performance, despite their transcriptional similarities.

  PublisherOA PDFDOI

• Single nucleus multi-omics regulatory landscape of the murine pituitary

  Nature Communications · 2021 · 74 citations

  • Biology
  • Computational biology
  • Genetics

  Abstract To provide a multi-omics resource and investigate transcriptional regulatory mechanisms, we profile the transcriptome, chromatin accessibility, and methylation status of over 70,000 single nuclei (sn) from adult mouse pituitaries. Paired snRNAseq and snATACseq datasets from individual animals highlight a continuum between developmental epigenetically-encoded cell types and transcriptionally-determined transient cell states. Co-accessibility analysis-based identification of a putative Fshb cis-regulatory domain that overlaps the fertility-linked rs11031006 human polymorphism, followed by experimental validation illustrate the use of this resource for hypothesis generation. We also identify transcriptional and chromatin accessibility programs distinguishing each major cell type. Regulons, which are co-regulated gene sets sharing binding sites for a common transcription factor driver, recapitulate cell type clustering. We identify both cell type-specific and sex-specific regulons that are highly correlated with promoter accessibility, but not with methylation state, supporting the centrality of chromatin accessibility in shaping cell-defining transcriptional programs. The sn multi-omics atlas is accessible at snpituitaryatlas.princeton.edu.

  DOI

• Comparative cellular analysis of motor cortex in human, marmoset and mouse

  Nature · 2021 · 818 citations

  • Biology
  • Genetics
  • Computational biology

  . Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

  DOI

• A multimodal cell census and atlas of the mammalian primary motor cortex

  Nature · 2021 · 564 citations

  • Neuroscience
  • Biology
  • Computational biology

  . First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.

  DOI

• Extraction of Distinct Neuronal Cell Types from within a Genetically Continuous Population

  Neuron · 2020 · 115 citations

  • Computer Science
  • Neuroscience
  • Biology
  PublisherOA PDFDOI

• Expanded encyclopaedias of DNA elements in the human and mouse genomes

  Nature · 2020 · 2538 citations

  • Computational biology
  • Biology
  • Genetics

  data. We have developed a registry of 926,535 human and 339,815 mouse candidate cis-regulatory elements, covering 7.9 and 3.4% of their respective genomes, by integrating selected datatypes associated with gene regulation, and constructed a web-based server (SCREEN; http://screen.encodeproject.org) to provide flexible, user-defined access to this resource. Collectively, the ENCODE data and registry provide an expansive resource for the scientific community to build a better understanding of the organization and function of the human and mouse genomes.

  DOI

• Perspectives on ENCODE

  Nature · 2020 · 222 citations

  • Biology
  • Computational biology
  • Genetics

  . The project has been extended to model organisms, particularly the mouse. In the third phase of ENCODE, nearly a million and more than 300,000 cCRE annotations have been generated for human and mouse, respectively, and these have provided a valuable resource for the scientific community.

  DOI

Recent grants

• Aradbidopsis 2010: Tools and Technologies to Enable Genome-Wide Screens in Arabidopsis

  NSF · $2.7M · 2004–2007

• NIH Grant R01GM042471

  NIH · $174k · 1992

• NIH Grant RC2GM092412

  NIH · $2.0M · 2011

• Arabidopsis 2010: The Arabidopsis Gene Collection/ORFeome Project

  NSF · $3.0M · 2005–2008

• The role of DNA methylation dynamics and patterning in postmitotic neuronal-maturation

  NIH · $3.4M · 2017–2023

Frequent coauthors

• Joseph R. Nery

  Salk Institute for Biological Studies

  235 shared

• José M. Alonso

  North Carolina State University

  231 shared

• Huaming Chen

  208 shared

• Bing Ren

  University of California, San Diego

  171 shared

• Chongyuan Luo

  145 shared

• Joanne Chory

  Salk Institute for Biological Studies

  127 shared

• Mathew G. Lewsey

  Australian Research Council

  112 shared

• Rosa Castanon

  Howard Hughes Medical Institute

  111 shared

Education

• NSF Postdoctoral Fellow, Biochemistry

  Stanford University School of Medicine

  1986

• Ph.D., Microbiology

  The Pennsylvania State University College of Medicine

  1982

• B.A., Biology

  College of New Jersey

  1978

Awards & honors

• Barbara McClintock Prize for Plant Genetics and Genome Studi…
• Arabidopsis Community Lifetime Achievement Award, 2024
• Ilchun Molecular Medicine Award, Korean Society for Biochemi…
• Chan Zuckerberg Initiative to expand Human Cell Atlas, 2019
• American Academy of Arts and Sciences, 2015

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