Research has possible applications for cancer treatment, fibrosis, and developmental birth defects
Image Credit: Edwin Remsberg
According to Lisa Taneyhill, professor in the Department of Animal & Avian Sciences at the University of Maryland, how cells not only move around the body to perform their various functions, but particularly how they go from being stationary to suddenly mobile (or motile), is an “age old question” in developmental biology. With her latest grant for $1.2 million from the National Science Foundation (NSF), Taneyhill is helping to tackle this question specifically in a cell type that gives rise to parts of our head, heart, gut, nervous system, and even skin pigment - the neural crest cell. Taneyhill will take a novel multidisciplinary approach from the subcellular level to the entire embryo by examining how an essential protein facilitates movement for these important cells. Additionally, the grant supports experiential research opportunities for high school and college students to train underrepresented groups and women in science, especially through a partnership with Trinity Washington University in Washington, DC, an all women’s university. Through this work, Taneyhill will help train the next generation of scientists while contributing to basic research in developmental biology that can be applied to the treatment and understanding of animal and human health conditions, ranging from developmental birth defects to fibrosis and to cancer, all of which involve cell migration.
“This research has many translational applications from the standpoint of animal and human disease,” says Taneyhill. “Cancer cells, for example, can undergo the process of becoming migratory or metastasize, and such cancers are much more difficult to treat because they are spreading throughout the body. So one of the goals of my lab is to understand what’s happening in a normal migratory event in a neural crest cell to have more unique tools at our disposal to treat diseases where cells are moving.”
This process of a cell transitioning from stationary to migratory that is so fundamental to developmental biology and diseases like cancer is known as the epithelial-to mesenchymal transition, or EMT for short. Taneyhill has been looking at EMT in neural crest cells for years, knowing that this process isn’t just important for this one cell type. “Nature likes to keep things relatively simple when developing organisms, so when it has something that works, why reinvent the wheel? You take the same players and pathways and deploy them in a different cell type,” explains Taneyhill. That makes this process a wide-reaching mechanism across development and disease.
Laying the groundwork with her previous work in EMT, this grant aims to examine the functionality of a specific protein that is essential to the EMT process in neural crest cells in many different ways. Cadherin-6B (Cad6B) is a protein that sits on the neural crest cell, half inside and half outside of the cell, acting as “molecular velcro” to help keep the cell stationary. When Cad6B remains intact, the cell doesn’t want to move. However, when enzymes come along and cut Cad6B in half, which has been observed in the embryo by Taneyhill’s lab, the cell not only loses its adhesive properties, but the two remaining pieces of Cad6B take on two different functions altogether that further facilitate the EMT process and mobility of the cell.
“Cells are very clever,” says Taneyhill. “They aren’t just going to cut proteins up without a purpose.” The inner piece goes deeper into the cell, turning on and off genes that are important to EMT, while the outer piece paves the way for the cell to move by breaking down pieces outside the cell that might get in its way. “The two aims of this grant are looking at these two different parts of the Cad6B protein, that once cut up, do very different things, but the goal is the same - to promote EMT and neural crest cell migration,” says Taneyhill.
In order to best examine what molecules the pieces of Cad6B are interacting with to further facilitate EMT and cell migration, Taneyhill is combining her expertise in developmental biology with Peter Nemes, a biochemist and associate professor in the College of Computer, Mathematical, Natural Sciences at UMD, to provide unique insight into this problem. “This grant brings together animal science and biochemistry to really tackle these challenging questions in the embryo that have applicability to other challenging processes and diseases that would not be possible without our respective expertise,” says Taneyhill.
As part of NSF’s initiative to fund both basic research and emphasize the broader impacts while training the future leaders in science, which Taneyhill mentions is unique in this granting institution, the funding will also help Taneyhill expand her lab’s experiential research opportunities for high school students and college undergraduates with particular emphasis on women and underrepresented groups in science.
“It’s very important to me that anyone, male or female, be given the opportunity to conduct research at the high school or undergraduate level. I have strong feelings about sharing that opportunity because I would not be here today without the research experiences I was given as an undergraduate. The mentoring and training these students receive now at each different career phase can help define their futures,” says Taneyhill.
Through her partnership with Trinity Washington University, an all women’s college in Washington, DC, Taneyhill will specifically be fostering future women in science, which is personally rewarding to her. “I talk about getting more women into science every chance I get,” says Taneyhill. “A lot of progress has been made, and my lab is actually entirely female right now at all levels, which is rare, but this is an ongoing discussion that has to continue because there are still inequities.”
Through this work, Taneyhill hopes to help address these inequalities while also contributing to basic science in developmental biology that can have an impact across animal and human disease. “Basic science is what drives how we are and how animals form, and there are so many different processes that go into that. But this work, with an emphasis on the broader impacts and translation as well as the basic science, is very exciting for developmental biology and beyond.”
This grant is funded by the National Science Foundation, Award IOS-1947169.