Kaelyn Sumigray, PhD, is an Assistant Professor in the Department of Genetics at Yale School of Medicine. Dr. Sumigray’s research program focuses on morphogenesis, how patterns arise during epithelial growth and maturation, and the functional and physiological requirement for those patterns. The main area of research is morphogenesis of the intestinal crypt, a pocket of epithelial cells in which intestinal stem cells reside. Her lab studies the cellular and molecular mechanisms through which epithelium forms the crypt architecture, which has significant implications for intestinal stem cell specification, maturation, and behavior.
To study stem cell niches, the Sumigray lab primarily uses mouse models and takes advantage of the sophisticated techniques available in this organism including lineage tracing, genetic cell ablation, conditional knockout, and inducible overexpression models. These are coupled with intestinal organoid culture approaches to study mechanisms of cell behavior. The Sumigray lab focuses on intestinal patterns through the lenses of both cellular architecture and cell state, and studies transcriptional changes that drive pattern formation using single cell RNA-sequencing approaches. There are specific challenges to studying postnatal intestinal morphogenesis, which takes place over several days, as there is currently no reliable way to continuously capture these dynamic events in vivo over that time scale. In addition, one arm of her lab studies the formation of a unique/rare cell type in the mammalian intestine. However, Dr. Sumigray said, “interestingly, mice lack this cell type, even though human intestines have it!” So her lab generated an organoid model and utilizes rats to study the specification of these cells.
Dr. Sumigray became fascinated by the cytoskeleton as an undergrad student. In graduate school she initially studied epidermal development, but when she identified a novel role for a gene in cytoskeletal organization in the epidermis, she wanted to see how well conserved its function was in other tissues. So, she said, “I looked in the intestine – and fell in love with its architecture. I wanted to understand how cell shapes within the intestine change to allow for crypts to invaginate – at the time, I was very obsessed with actomyosin contractility and apical constriction. I still am.” Her independent research started with a pure morphogenesis focus that has grown to include questions about how morphogenesis impacts stem cell function and behavior, and how that impacts other patterning events in the mouse intestine.
Dr. Sumigray has persevered through challenges as a Junior PI. She opened her lab at Yale School of Medicine in September 2019, and then had to shut it down after only 6 months because of the pandemic, which was incredibly challenging and a unique situation. Also, “I get excited about lots of scientific questions, and I think my lab’s research program reflects that,” she said. But in the beginning it was difficult (and is still difficult) to decide how to balance expansion into new areas with really sticking to one or two key areas of focus. One thing that was surprising to Dr. Sumigray when she started her lab was figuring out how to match a project with a lab member. She said, “projects have ‘personalities’ just like people, and there needs to be synergy between the two for them to be productive and fulfilling for all involved.” Running a lab has also helped Dr. Sumigray develop an approach to handle conflict within the lab; she keeps the lines of communication open and accessible according to her philosophy that lowering the barrier to communicating about conflict is important.
The Sumigray lab has recently made several exciting discoveries through the careful deep characterization of phenotypes, cells, and processes of intestinal morphogenesis. For instance, the lab has identified a molecular pathway that regulates the paths that cells take as they move from the crypt up the villi, which are finger-like projections of cells into the intestinal lumen that perform nutrient absorption functions. This discovery prompted the lab to adopt biophysical approaches to establish the intestinal epithelium as a model for studying collective cell migration. This research direction aims to understand how cells move in the intestine and how cell turnover is coupled with cell division. The Sumigray lab provides ample opportunities for both undergraduate and graduate students to engage in research. Currently, the lab hosts two undergraduate and five graduate students. Undergraduate students are paired with graduate students or postdoctoral researchers, allowing them to learn and master one of the lab’s favorite techniques: microscopy.