research
How does membrane organization control epithelial-to-mesenchymal transition and cell migration during development and disease?
EMT and Cell Migration
The Question
Epithelial-to-mesenchymal transition, or EMT, is a major cellular lifestyle change that results in cells with the ability to migrate long distances in the body. This process is critical for normal embryonic development and for the formation of many organs. However, EMT mechanisms are often co-opted in disease states such as cancer metastasis. How does membrane organization control EMT and cell migration during development and disease?
Our Approach
We use the chicken neural crest as a tractable model system to study the mechanisms of EMT and cell migration. The neural crest is an embryonic cell population with remarkable multipotency and migratory ability, enabling it to contribute to diverse organ systems including the craniofacial skeleton and the peripheral nervous system (Piacentino et al., 2020). By combining chick embryology with live imaging, molecular biology, and biochemistry, we can watch this transition unfold in real time. Insights gained from studying neural crest cells have the potential to inform novel therapeutic approaches to combat both congenital disorders and metastatic diseases.
Lipid Metabolism
The Question
EMT is often punctuated by changes in expression of diverse lipid metabolizing enzymes, raising the question: what is the function of lipid metabolism during EMT?
What We’ve Found
We have described the mechanism by which the production of the membrane lipid ceramide by the enzyme nSMase2 is necessary for neural crest EMT (Piacentino et al., 2022). Our work shows that ceramide production in the neural crest is necessary for endocytosis, which promotes cell signaling, transcriptional regulation, de-adhesion, and delamination. Using transcriptomics, reporter constructs, and gene editing, we are now deciphering how different lipid metabolizing genes are transcriptionally regulated across embryonic space and time (Piacentino et al., 2024).
Membrane Biophysics
The Question
Changing lipid metabolism has the potential to modulate the biophysical properties of the plasma membrane. How does temporally-controlled lipid metabolism alter membrane properties such as fluidity and rigidity, as well as the lateral organization of proteins and lipids within it?
What We’ve Found
We have found that ceramide production by nSMase2 increases plasma membrane fluidity to influence directional neural crest migration (manuscript in preparation).
