Jeffrey Allen Farrell, Ph.D.

Animals consist of a collection of cells with beautifully diverse shapes, structures, and functions, and this diversity is rebuilt from scratch by every embryo. Understanding the genetic programs that direct this process is the central mystery of developmental and regenerative biology. How are decisions about what cell type to adopt controlled? What genetic programs direct the morphological and functional specialization of different cells? Our lab combines single-cell genomics, imaging, genetic, and classical embryological approaches to investigate the genetic control of cell specification and differentiation during vertebrate embryogenesis. We focus on zebrafish embryos as a model system to study these questions, because among vertebrates, they are easy to culture, image, and manipulate both embryologically and genetically.

The single-cell revolution in developmental biology has given us new access and new tools to address these questions. I previously developed approaches to identify transcriptional trajectories from high temporal resolution single-cell RNA sequencing. These are the ‘highways’ or most likely paths through gene expression that cells take during development. These trajectories provide insight into the genetic programs that regulate cells’ choice of cell type and then their downstream functional transformations at a wider breadth than was previously achievable. Our lab has been a leader in the generation of large-scale single-cell genomic datasets describing development in zebrafish embryos and larvae, as well as the creation of tools to make them broadly accessible, including Daniocell and DaniocellDesktop.

The lab is currently focused on:

- Improving our approaches and tools used to investigate developmental decisions and RNA stability during development and applying them to new developmental questions.

- Identifying how cell types within the intestine and its surrounding support tissues are specified during development, homeostasis, and regeneration. We currently have particular focus on best4+ cells, a recently uncovered intestinal cell type conserved across most vertebrates.

- Identifying how cells’ developmental histories influence their downstream fate and decisions, including whether insults during development alter their future fate and whether indecision during developmental decisions alters cells long-term, potentially making them more susceptible to alterations or errors that give rise to disease.

Dr. Farrell received a B.A. in Biochemistry from Columbia University in 2006. He performed his graduate work at the University of California, San Francisco in the lab of Patrick O’Farrell. There, he found that the dramatic slow-down of DNA replication at the Drosophila mid-blastula transition was triggered by regulated proteolysis of Cdc25 and a resultant drop in Cdk1 activity. Dr. Farrell then performed his postdoctoral work in the lab of Alexander Schier at Harvard University, in deep collaboration with the lab of Aviv Regev at the Broad Institute. There, he worked on developing and applying single-cell RNAseq approaches for studying developmental biology, including one of the first approaches for spatial inference from single-cell RNAseq data (Seurat), an approach to find transcriptional trajectories during development (URD), and one of the first whole-embryo single-cell RNAseq developmental atlases. Dr. Farrell is now an Earl Stadtman Investigator in NICHD, where he heads the Unit on Cell Specification and Differentiation. His work has been recognized by Science as part of their 2018 Breakthrough of the Year, by the International Zebrafish Society with the 2019 Chi-Bin Chien Award “for significant contributions to the field of zebrafish research and exhibition of generosity and openness by a future leader in the zebrafish field,” and by the Society for Developmental Biology with the 2026 Elizabeth D. Hay New Investigator Award “for outstanding research in developmental biology during the early stages of his independent career.”