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Ed Lein, Ph.D.

Investigator

Ed Lein joined the Allen Institute in 2004 and provides scientific guidance and oversight for the creation of large-scale gene expression atlases of the mammalian brain as online resources for the scientific community. Lein was part of the team that generated the inaugural Allen Mouse Brain Atlas, and now leads efforts to extend these anatomical and gene expression atlasing efforts to the developing human and non-human primate brain. Particular interests of Lein’s work at the Allen Institute include the use of large-scale gene expression data to map functional brain divisions, define specific neuronal subtypes, and compare cellular-level gene expression patterns from rodents to humans to identify molecular pathways unique to humans. Lein received a B.S. in biochemistry from Purdue University and a Ph.D. in neurobiology from the University of California at Berkeley. His postdoctoral work at the Salk Institute for Biological Studies focused on molecular profiling of specific hippocampal and neocortical cell types and the generation of molecular genetic tools for functional manipulation of specific neuronal subtypes. Lein is also an Affiliate Assistant Professor in the Department of Physiology and Biophysics at the University of Washington.

Research

Expertise

  • Developmental neurobiology
  • Structural and cellular neuroanatomy
  • Transcriptomics

Research Programs

  • Cell types
  • Neural coding
  • Atlasing

Research Interests

I have been involved from the ground level in three major atlasing projects at the Allen Institute, originally as part of the team that generated the inaugural Allen Mouse Brain Atlas. Subsequently I led the production of the BrainSpan Atlas of the Developing Human Brain, a consortium-based effort to profile the transcriptome of the pre- and postnatal developing human brain, and the NIH Blueprint Non-Human Primate Atlas, which aims to carefully profile spatiotemporal gene expression patterning in the pre- and postnatal rhesus monkey forebrain. I am now spearheading the human cell types project, which aims to build upon these foundational gene expression studies in human brain by developing and implementing methods for the quantitative phenotypic analysis of individual cells of the human neocortex.

A major focus of my research is using high-resolution anatomical transcriptome data to understand the molecular and cellular architecture of the mammalian neocortex and hippocampus. What is the molecular logic underlying cortical structure and function? What are the developmental mechanisms that direct the specification and maturation of cortical cell types, and is it possible to derive a transcription factor code that drives the cellular decision tree underlying progressive precursor fate restriction and specification of specific cortical neuron types? What is unique about human molecular and cellular cortical architecture, and the developmental dynamics that give rise to the massive expansion of the human neocortex?

The human cell types project aims to study the fine structure of the human neocortex through the quantitative molecular, anatomical and functional analysis of single cells in postmortem and living neurosurgery-derived cortical tissues. Combining systematic data generation and advanced machine learning techniques, major goals are to derive a quantitative classification of human cortical cell types and to understand functional population dynamics in the living human neocortex. What are the unique genetic, structural and functional characteristics of the human neocortex that enable our great cognitive capabilities and could be specifically affected in neurological or neuropsychiatric diseases? What is different about cellular properties and functional circuit organization of the human neocortex compared to the dominant genetic model system for biomedical research, the mouse? By developing tools and techniques for the reliable preservation and cellular and circuit interrogation of human cortical tissues the project aims to broadly catalyze research on the human brain.