Developmental single-cell transcriptomics in the Lytechinus variegatus sea urchin embryo.

I study the evolution of genes and genomes with the broad aim of understanding the origins of biological diversity. My approach focuses on changes in the expression of genes using both empirical and computational approaches and spans scales of biological organization from single nucleotides through gene networks to entire genomes. At the finer end of this spectrum of scale, I am focusing on understanding the functional consequences and fitness components of specific genetic variants within regulatory sequences of several genes associated with ecologically relevant traits. At the other end of the scale, I am developing molecular and analytical methods to detect changes in gene function throughout entire genomes, including statistical frameworks for detecting natural selection on regulatory elements and empirical approaches to identify functional variation in transcriptional regulation. At intermediate scales, I am investigating functional variation within a dense gene network in the context of wild populations and natural perturbations. My research leverages the advantages of several different model systems, but primarily focuses on sea urchins and primates (including humans).

We ask how the embryo works. Prior to morphogenesis the embryo specifies each cell through transcriptional regulation and signaling. Our research builds gene regulatory networks to understand how that early specification works. We then ask how this specification programs cells for their morphogenetic movements at gastrulation, and how the cells deploy patterning information.
Current projects examine 1) novel signal transduction mechanisms that establish and maintain embryonic boundaries
mold the embryo at gastrulation; 2) specification of primary mesenchyme cells in such a way that they are prepared to execute an epithelial-mesenchymal transition, and then study mechanistically the regulation of that transition; 3) the specification of endoderm necessary for invagination of the archenteron; 4) formation of the oral/aboral ectoderm and the means by which patterning information is distributed three dimensionally around the embryo. That information is necessary for patterning and inducing skeletogenesis.
Other projects examine neural tube folding with the goal of identifying genes associated with neural tube defects. Finally, a large current effort in systems biology is being expended with the goal of enlarging our knowledge of early networks and how they interact.