Research Program

 

Our research is directed at elucidating mechanisms underlying morphogenetic processes in development. We primarily use the model system C. elegans in our research, and combine powerful genetic and systems biology approaches with live-cell imaging to address three main topics:   

Cell invasion and Tissue Connections:  A major focus of the lab is the understanding of 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. We have begun to apply what we learn in the anchor cell to better understand how cancer cells become invasive. Our group also examines other aspects of uterine-vulval attachment, including control of cell division, cell-cell signaling, basement membrane remodeling, and how basement membranes fuse to connect distinct tissues.

Stem Cell-Niche Interactions:   We are 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 and their progeny.  We have also made the surprising discovery that germ cells that escape their niche appear capable of inducing naïve somatic cells to take on aspects of niche cell behavior by creating cellular pockets that enwrapment the stem cells—a behavior we suspect underlies the ability of metastatic cancer cells to ectopically establish stem cell niches at distant sites. We are currently conducting screens and performing live-cell imaging studies to understand this novel behavior.

Basement Membrane/Extracellular Matrix Biology:  Basement membrane is a dense, sheet-like extracellular matrix that underlies all epithelia and surrounds most tissues. Basement membrane emerged at the time of animal multicellularity and was likely required to support complex tissue formation through its regulation of cell polarity, cell differentiation, cell survival, tissue mechanics, and tissue barrier functions.  Despite its importance, we know very little about how this extracellular matrix is built, grows, stretches, and how it is turned over and specialized for unique functions.  Highlighting its importance, numerous human diseases are associated with basement membrane dysfunction, including cancer, Alzheimer’s, fibrosis, and diabetes.  To understand fundamental properties of basement membrane regulation, we are using genome editing to functionally tag every major and minor basement membrane matrix component and receptor with mNeonGreen and other fluorphores.  We are currently examining basement membrane dynamics, assembly, turnover, and how basement membrane fuses to connect tissues.

The Duke University & Research Triangle Area:  Members of our group are trained in a diverse range of scientific approaches and join a vibrant scientific community at Duke University, the Research Triangle region and the worldwide group of worm researchers.