The sherwood lab has three primary research focuses:
- Understanding how cells invade and remodel basement membrane boundaries
A major focus of the lab is understanding mechanisms underlying uterine-vulval attachment. A key aspect of this process is the invasion of a single uterine cell, the anchor cell, through the uterine and vulval basement membranes, which initiates uterine-vulval connection. The ability of cells to invade through basement membrane is crucial for many developmental processes and remains one of the least understood aspects in the progression of cancer. Anchor cell invasion is emerging as a powerful system to uncover novel molecular mechanisms controlling invasive behavior and we have begun to apply what we learn in the anchor cell to better understand how cancer cells become invasive, as well as initiated the first in vivo chemical screens to identify compounds that specifically block cell invasive behavior.
Our group also examines later aspects of uterine-vulval attachment and we have focused on control of cell division, cell-cell signaling, cell-cell attachments and basement membrane remodeling.
- Eludicating communication and dynamic cellular behavior between germ stem cells and their somatic partners
We have initiated studies examining the cell biological aspects of cell-cell and cell-basement membrane establishment of the germ stem cell niche. We are particularly interested in how somatic and germ cells interact to maintain the germ stem cells. These interactions are highly dynamic and are regulated by the state of the germ cells and the nutritional status of the worm. We have even found that when germ cells escape their normal niche, they are capable of inducing other somatic cells to inappropriately form a niche. These observations suggest a rich and likely ancient communication system exists between germ cells and their somatic partners.
- Understanding whole organism coordinated cellular quiescence-stopping, pausing and reinitiating development
We are examining the developmental response of late larvae to starvation. We have identified specific developmental checkpoints that late larvae enter in response to the absence of food. These arrest points halt many different cellular behaviors, including cell division, cell-cell fusion, cell migration and cell invasion. We have found that the cells can be paused/quiescent for many days, and then rapidly recover and initiate their appropriate morphogenetic program upon the reintroduction of food. Notably, arrest has the effect of doubling the lifespan of the worm. These studies have many fascinating implications in our understanding of how cells arrest at specific developmental time-points, how an organism and cells enter and exit quiescent states, and how these impinge on life-span.