About

We are motivated by questions aimed at understanding how cis-regulatory element evolution impacts organismal phenotypes, how developmental mechanisms evolve, and how comparative evolutionary genomics can inform our understanding of the genotype to phenotype map. Specifically, we use comparative high-throughput sequencing and functional genomics to understand how differences in transcription and regulation lead to differences in phenotypes.

Research topics

• Biology
• Genetics
• Evolutionary biology
• Neuroscience
• Cell biology
• Biochemistry
• Computational biology

Selected publications

• Ecological Trait Differences Are Associated with Gene Expression in the Primary Visual Cortex of Primates

  Genes · 2025-01-22

  articleOpen accessSenior authorCorresponding

  Primate species differ drastically from most other mammals in how they visually perceive their environments, which is particularly important for foraging, predator avoidance, and detection of social cues. BACKGROUND/OBJECTIVES: Although it is well established that primates display diversity in color vision and various ecological specializations, it is not understood how visual system characteristics and ecological adaptations may be associated with gene expression levels within the primary visual cortex (V1). METHODS: We performed RNA-Seq on V1 tissue samples from 28 individuals, representing 13 species of primates, including hominoids, cercopithecoids, and platyrrhines. We explored trait-dependent differential expression (DE) by contrasting species with differing visual system phenotypes and ecological traits. RESULTS: Between 4-25% of genes were determined to be differentially expressed in primates that varied in type of color vision (trichromatic or polymorphic di/trichromatic), habitat use (arboreal or terrestrial), group size (large or small), and primary diet (frugivorous, folivorous, or omnivorous). CONCLUSIONS: Interestingly, our DE analyses revealed that humans and chimpanzees showed the most marked differences between any two species, even though they are only separated by 6-8 million years of independent evolution. These results show a combination of species-specific and trait-dependent differences in the evolution of gene expression in the primate visual cortex.

  PublisherOA PDFDOI

• Transcriptomic changes across subregions of the primate cerebellum support the evolution of uniquely human behaviors

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-03-04 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Background: Compared to other primates, humans display unique behaviors including language and complex tool use. These abilities are made possible in part by the cerebellum. This region of the hindbrain, comprising the flocculus, vermis, and lateral hemispheres, has expanded throughout primate evolution, particularly in great apes. Given the cerebellum's architecture-differing in connectivity, neuron content, and functions across subregions-examining subregional differences is crucial to understanding its evolutionary trajectory. Results: We performed bulk RNA-seq across samples from six primate species, representing 40-50 million years of evolutionary history, across four subregions of the cerebellum (vermis, flocculus, right lateral hemisphere, left lateral hemisphere). We analyzed changes in gene expression with respect to evolutionary relationships via the Ornstein-Uhlenbeck model and found that, on average, 8.5% of orthologous genes are differentially expressed in humans relative to other non-human primates. Subregion-specific gene expression patterns reveal that the primate lateral hemispheres exhibit significant differences in synaptic activity and glucose metabolism, which in turn are highly implicated in neural processing. Conclusions: This study provides a novel perspective on gene expression divergences across cerebellar subregions in multiple primate species, offering valuable insights into the evolution of this brain structure. Our findings reveal distinct subregional transcriptomic patterns, with the lateral hemispheres emerging as key sites of divergence across the six primate species. The enrichment of genes related to synaptic activity, glucose metabolism, locomotion, and vocalization highlights the cerebellum's crucial role in supporting the neural complexity underlying uniquely human and other species-specific primate behaviors.

  PublisherOA PDFDOI

• Exploring the Expanded Role of Astrocytes in Primate Brain Evolution via Changes in Gene Expression

  Brain Behavior and Evolution · 2025-02-05

  reviewOpen accessSenior author

  BACKGROUND: Astrocytes are a subtype of glial cells, which are non-neuronal cells that do not produce action potentials. Rather, astrocytes are involved in various functions vital to a functioning brain including nutrient supply to neuronal cells, blood-brain barrier maintenance, regulation of synaptic transmission, and repair following CNS injury. SUMMARY: While astrocytes have been examined extensively in rodents, it is now clear that there is a large amount of astrocyte heterogeneity and increased complexity in mammals and primates. Astrocytes have expanded in the human lineage with respect to density, soma volume, and the ratio of astrocytes to total glial cells. The human prefrontal cortex also possesses an overall increased glia:neuron ratio relative to other primates, coinciding with allometric expectations based on overall brain size. KEY MESSAGES: What are the underlying changes in astrocytes in primate evolution? For this review, we will focus on the evolution of gene expression and gene regulation in astrocytes as a read out of the phenotypic changes seen in cellular morphology. This is an exciting time to understand this cell type in a more dynamic and complex way with new technologies such as induced pluripotent stem cells and single-cell RNA sequencing. Furthermore, understanding the evolution of astrocytes across primates will help explain their role in neurological disease as alterations in astrocyte function are implicated in many neurodegenerative states such as Alzheimer's disease and Parkinson's disease.

  PublisherOA PDFDOI

• Shaping the Neocortex: Radial Glia and Astrocytes in Development and Evolution

  Journal of Neuroscience · 2025-11-12 · 4 citations

  articleOpen access

  The evolutionary expansion of the mammalian neocortex-especially in primates-underpins the emergence of advanced cognitive abilities. This process involved not only increased cortical surface area and neuronal output but also enhanced structural adaptations, such as cortical folding and glial morphological complexity. In this review, we examine the central roles of radial glia (RG) and astrocytes in driving neocortical expansion and evolution. We highlight the emergence of primate- and human-specific genes, which contribute to enhanced RG proliferation and neurogenesis in these species. We further explore how epigenetic regulation and dynamic chromatin architecture modulate RG behavior across species. At the cellular level, we discuss how morphological features-particularly the basal processes and specialized protrusions of RG-facilitate access to diverse extrinsic signals, promoting proliferative capacity and cortical complexity. We then turn to cortical folding, focusing on the role of astrocytes, and the functional relevance of folds in supporting brain homeostasis. Finally, we address astrocyte diversity, development, and evolutionary adaptation, with special emphasis on sex differences and primate-specific features. Comparative transcriptomic and morphological studies reveal that human astrocytes exhibit unique molecular signatures, expanded metabolic capacity, and higher morphological complexity. Together, these insights underscore the multifaceted contributions of RG and astrocytes to the evolutionary elaboration of the neocortex. They further provide a framework for understanding how cellular innovations shaped the modern primate brain in general, and human brain specifically.

  PublisherOA PDFDOI

• Author response for "Heterogeneity of brain extracellular matrix and astrocyte activation"

  2024-04-01

  peer-review
  PublisherDOI

• Tempo and mode of gene expression evolution in the brain across primates

  eLife · 2024-01-26 · 15 citations

  articleOpen accessSenior author

  Primate evolution has led to a remarkable diversity of behavioral specializations and pronounced brain size variation among species (Barton, 2012; DeCasien and Higham, 2019; Powell et al., 2017). Gene expression provides a promising opportunity for studying the molecular basis of brain evolution, but it has been explored in very few primate species to date (e.g. Khaitovich et al., 2005; Khrameeva et al., 2020; Ma et al., 2022; Somel et al., 2009). To understand the landscape of gene expression evolution across the primate lineage, we generated and analyzed RNA-seq data from four brain regions in an unprecedented eighteen species. Here, we show a remarkable level of variation in gene expression among hominid species, including humans and chimpanzees, despite their relatively recent divergence time from other primates. We found that individual genes display a wide range of expression dynamics across evolutionary time reflective of the diverse selection pressures acting on genes within primate brain tissue. Using our samples that represent a 190-fold difference in primate brain size, we identified genes with variation in expression most correlated with brain size. Our study extensively broadens the phylogenetic context of what is known about the molecular evolution of the brain across primates and identifies novel candidate genes for the study of genetic regulation of brain evolution.

  PublisherDOI

• Heterogeneity of brain extracellular matrix and astrocyte activation

  Journal of Neuroscience Research · 2024-05-01 · 8 citations

  article

  From the blood brain barrier to the synaptic space, astrocytes provide structural, metabolic, ionic, and extracellular matrix (ECM) support across the brain. Astrocytes include a vast array of subtypes, their phenotypes and functions varying both regionally and temporally. Astrocytes' metabolic and regulatory functions poise them to be quick and sensitive responders to injury and disease in the brain as revealed by single cell sequencing. Far less is known about the influence of the local healthy and aging microenvironments on these astrocyte activation states. In this forward-looking review, we describe the known relationship between astrocytes and their local microenvironment, the remodeling of the microenvironment during disease and injury, and postulate how they may drive astrocyte activation. We suggest technology development to better understand the dynamic diversity of astrocyte activation states, and how basal and activation states depend on the ECM microenvironment. A deeper understanding of astrocyte response to stimuli in ECM-specific contexts (brain region, age, and sex of individual), paves the way to revolutionize how the field considers astrocyte-ECM interactions in brain injury and disease and opens routes to return astrocytes to a healthy quiescent state.

  PublisherDOI

• TATA-binding associated factors have distinct roles during early mammalian development

  Developmental Biology · 2024-04-07 · 8 citations

  articleOpen access
  PublisherOA PDFDOI

• Tata-Binding Associated Factors are Essential for Distinct Roles During Early Mammalian Development

  SSRN Electronic Journal · 2024-01-01

  preprintOpen access
  PublisherDOI

• Author response: Tempo and mode of gene expression evolution in the brain across primates

  2023-09-07

  peer-reviewOpen accessSenior author
  PublisherDOI

Recent grants

• The genomics of metabolic change in human and non-human primate brain evolution

  NSF · $473k · 2022–2026

• Doctoral Dissertation Research: Investigating astrocyte-mediated adaptive changes in primate brain metabolism

  NSF · $32k · 2019–2020

• Positive Selection on Gene Regulation and the Evolution of the Human Brain

  NSF · $330k · 2018–2022

Frequent coauthors

• Gregory A. Wray

  Duke University

  28 shared

• Patrick R. Hof

  Icahn School of Medicine at Mount Sinai

  20 shared

• Mary Ann Raghanti

  Kent State University

  17 shared

• Trisha M. Zintel

  17 shared

• Amy L. Bauernfeind

  Washington University in St. Louis

  16 shared

• Olivier Fédrigo

  14 shared

• Ralph Haygood

  14 shared

• Shelly R. Peyton

  University of Massachusetts Amherst

  10 shared

Labs

• BABBITT LABPI

  Courtney Babbitt, Ph.D