Angelman Updates with Dr. Terry Jo Bichell, featuring Dr. Albert Keung

Quick Overview

In this interview, Dr. Terry Jo Bichell speaks with Dr. Albert Keung about his research on Angelman Syndrome. Dr. Keung discusses his work with organoids, which are miniature models of the brain created from stem cells. He explains that his lab is focused on improving these models to better understand the biology of Angelman Syndrome. Dr. Keung also discusses his research on the timing of UBE3A protein expression and silencing in human organoids, as well as the potential for therapeutic interventions. He mentions the use of landing pads, which allow for more efficient editing of the genome, and the importance of studying the diversity of Angelman Syndrome mutations. Overall, Dr. Keung’s research aims to provide insights into the underlying mechanisms of Angelman Syndrome and develop potential treatments.

Introduction

Dr. Terry Jo Bichell, a neuroscientist and mother of a son with Angelman Syndrome, is excited to interview researchers in the field of Angelman Syndrome. In this interview, she speaks with Dr. Albert Keung, a neuroscientist and synthetic biologist at North Carolina State University. Dr. Keung discusses his work on developing human stem cell models of Angelman Syndrome and the importance of understanding the genetic diversity of the disorder.

Getting into the Angelman Field

Dr. Keung explains that his interest in Angelman Syndrome began during his graduate work, where he studied neural stem cells. He wanted to improve human stem cell models of the brain and was drawn to Angelman Syndrome due to the strong research presence at UNC Chapel Hill, which is located near his institution. Additionally, the focus of his lab on studying epigenetics aligned well with the central problem of Angelman Syndrome.

Research on Organoids

Dr. Keung’s lab has been working with organoids, which are miniaturized versions of organs grown in a dish. These organoids are derived from human stem cells and can mimic the development of the brain. Dr. Keung’s team has been studying the localization of the UBE3A protein, which is central to Angelman Syndrome, within these organoids. They have also tested drug responses using the organoids, including the reactivation of UBE3A using a chemical called into Tcan.

Understanding UBE3A Localization

One of the key findings of Dr. Keung’s research is the timing of UBE3A localization in the organoids. They found that between the first and second trimester equivalents in human development, the UBE3A protein moves into the nucleus of neurons and the paternal UBE3A is silenced. This information is crucial for understanding the function of the protein and developing therapeutics.

The Complexity of Organoids

Dr. Keung clarifies that while organoids are a valuable model for studying human development, they are not exact replicas of the brain. They lack the complexity and connectivity of a fully developed brain. However, they can still provide insights into the behavior of neurons and the effects of genetic changes.

Creating Models of Angelman Syndrome

Dr. Keung’s lab has been working on generating stem cell lines that mimic the genetic changes seen in Angelman Syndrome. They are collaborating with other researchers and using different approaches, such as editing the genome or introducing specific mutations, to create a diverse range of models. This will allow them to study the effects of different genetic backgrounds and identify potential treatment options.

The Power of Landing Pads

To accelerate the process of creating these models, Dr. Keung’s lab is using landing pads. Landing pads are sequences of DNA that facilitate the editing of the genome. By inserting landing pads into cells, they can more efficiently introduce specific genetic changes. This approach allows for the rapid generation of different models and enables collaboration among researchers.

Translational Applications

Dr. Keung emphasizes the potential translational applications of his research. By studying the effects of different genes and mutations, his lab hopes to identify new therapeutic targets and develop screening methods for drug discovery. The ability to control gene expression and study the physiological effects of specific genes is a valuable tool in understanding and treating Angelman Syndrome.

Conclusion

Dr. Keung’s work on developing human stem cell models of Angelman Syndrome provides valuable insights into the disorder’s genetic diversity and potential treatment options. His research on organoids and the use of landing pads for genome editing offer new avenues for studying the disorder and accelerating the development of therapeutics. Through collaboration and innovative approaches, Dr. Keung and his colleagues are making significant contributions to the field of Angelman Syndrome research.