A new grant from the Eagles Autism Foundation will help advance Waisman research on the genetic cause of autism

By Emily Leclerc | Waisman Science Writer

Xinyu Zhao, PhD
Investigator Xinyu Zhao, PhD in her Waisman Center laboratory. (Photo © Andy Manis)

Studying the biological underpinnings of autism is exceptionally complex with more than 1000 genes thought to be associated with autism. A new grant from the Eagles Autism Foundation (EAF), will help Waisman investigator Xinyu Zhao, PhD, look closer at one of the genes thought to be associated with autism – MBD1. “My lab has been working on this for a long time. I actually worked on this as a postdoc,” says Zhao, a professor of neuroscience at UW-Madison. “We know this gene is important and this grant will help us pinpoint why.”

MBD1 is heavily involved in gene expression. It helps regulate a variety of different genes and is involved in neurogenesis and neuron maturation (the growth and development of new neurons). “Our central goal is to understand how MBD1 is regulating brain development and how exactly it relates to autism,” Zhao says.

Specifically, MBD1 regulates a set of genes that produce proteins called clustered protocadherins. This group of proteins is responsible for giving neurons a cell-specific identity to allow for distinction between self and non-self. When there is a mutation in the MBD1 gene, individuals have extensive behavioral deficits and are often diagnosed with autism or a developmental delay. But the mechanisms behind this relationship remain unclear.

Eagles Autism Foundation“The Eagles Autism Foundation is dedicated to funding the most innovative autism research and care programs in the Philadelphia area, across the country, and now, globally,” said Kirsten Saraceni, M.S., BCBA, LBS, Eagles Autism Foundation Director of Scientific Programs. “We are proud to support the work of Waisman investigator Xinyu Zhao, PhD and team, through our grant process, as they make strides in advanced autism research.”

This project will employ two powerful techniques to study MBD1 – spatial genomics and patch-seq. Spatial genomics will allow Zhao and the project team to identify where exactly in the brain MBD1 is influencing expression. “We found earlier that MBD1’s targets show spatial differences. This technique will allow us to identify where in space the gene expression is in the brain and not just at a teeny expression level but in a broader way,” says Yu Gao, PhD, a scientist in Zhao’s lab and the project lead.

Moosa Syed, a research intern in Zhao’s lab and assistant to Gao on this project, is particularly looking forward to working on spatial genomics. “Through the spatial genomics aspect of this grant, we will be able to look at the clustered protocadherins in the patterns they are being expressed in and by which brain regions,” Syed says. “We’ll be looking at it in the context of MBD1 and neurodevelopmental disorders but I think this information is applicable to scientists working on the brain in general which is exciting.”

Patch-seq is the method used to look at the individual features of neurons. It will allow the team to look closely at the gene expression, morphology (a neuron’s physical characteristics), and electrophysiological features of the neurons they are studying. “With this tool we will be able to identify how the MBD1 mutation affects these three features,” Gao says. They will perform this work in collaboration with two experts in electrophysiology, Dr. Qiang Chang the director of the Waisman Center and scientist Dr. Qiping Dong.

Yu Gao, PhD
Yu Gao, PhD

For Zhao, Gao, Syed, and the team, this project is very exciting and it would not have been possible without the support of the Eagles Autism Foundation. This foundation was founded by Philadelphia Eagles Chairman and CEO, Jeffrey Lurie. Through Mr. Lurie’s stewardship, EAF aims to inspire and engage the community, while providing much-needed support to make a lasting impact in the field of autism.

The project has the potential to open a lot of important doors and allow Zhao and her team to ask bigger questions in the future. “I have to say this is very visionary for a group like the Philadelphia Eagles football team. They understand the importance of basic science and that you can’t really develop a treatment until you understand the underlying science. This grant and the foundation are unique in that way,” Zhao says. “Go Eagles!”


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