Developmental biologist Professor Anna Beaudin and her lab are making breakthrough discoveries in a growing field of research that could lead to exciting developments in such medical puzzles as cancer treatments, regenerative medicine and the cause of autism.
She examines the mechanisms of how distinct blood stem cells are established during fetal development, how and why they give rise to the cells that make up human immune systems, how these cells work and what happens when something goes wrong.
“There’s so much we still don’t know,” Beaudin said. “We don’t know how these cells are made as fetuses develop and what confers their unique properties on them, and we don't know what these cells do in either normal or diseased adult tissues.”
Developmental blood stem cells have an important function in establishing the immune system: They form specific immune cells that make up a person’s first phase of immunity, and often live in human tissues throughout a person’s lifetime. Her recent work focuses on a subset of these cells known as tissue resident macrophages. Macrophages are an important cellular component of the innate arm of the immune system.
The tissue-resident macrophages both educate the tissue on how it’s supposed to work during development and learn from the tissue as it develops. For example, these macrophages in the liver learn how to recycle iron, because the liver is the primary iron-recycling organ in the body. In the developing brain, where these cells are known as microglia, they function to prune malformed synapses to ensure correct brain development.
Recently, Beaudin and her students discovered a novel signaling pathway that regulates the development of tissue resident macrophages. The trigger is a chemical known as IL7, or interleukin 7. Interestingly, in adults, IL-7 signaling is used exclusively to direct cells on the path to adaptive immunity.
IL7 signaling is also part of the fetal development system, but it serves a very different function — it makes the innate immune system microphages. But how and why it switches functions is just one of many questions Beaudin wants to answer.
A new paper she and two of her students and collaborators authored appeared in the journal Development explain the discovery.
To build on this work, she and her lab have received a prestigious, $1.9 million RO1 grant from the National Institutes for Health’s National Heart, Lung and Blood Institute. The money will support her and her undergrad and grad students, as well as postdoctoral researchers for the next five years.
“We’re going to look at what steps IL7 is used in each pathway and discover what role it plays in each,” she said.
“With this grant, we’ll be able to continue investigating the development of the immune system and build the foundation for manipulating the immune system for health and treatment of disease,” said fourth-year graduate student and lab member Gabriel Leung.
RO1 grants are the oldest grant mechanism in the NIH.
“In addition to the excellent and important work Professor Beaudin is doing in this area of developmental immunology, this significant award from the NIH is a clear indication of the impactful work our faculty are performing and the respect they are establishing from the scientific community, in general, in a relatively short period of time,” Department of Molecular and Cell Biology Chair Professor Rudy Ortiz said. “It also indicates that the significant time and efforts our faculty in MCB are putting forth is translating into great successes. This is one of many such awards our faculty has earned in the past couple of years and it is helping to establish our faculty as among the top biomedical research programs, gaining national and international recognition. I’m excited for all of them and for the future of our department and campus as we continue to make great strides in our research programs.”
Answering such intricate questions sounds ambitious, but Beaudin, a Pew scholar, Hellman fellow, member of the School of Natural Sciences and an affiliate of the Health Sciences Research Institute , said her lab is already well on its way.
Of the six undergrads in her lab, three are working on this project, along with Leung, the first author on the Development paper, and postbaccalaureate specialist Clint Valencia, a UC Merced alum and the second author.
“I have amazing students,” she said. “They work incredibly hard. They are really high-capacity, so we get a lot done.”