Advancing Human Stem Cell-Derived Platforms for Angelman Syndrome Research

Quick Overview

Dr. Albert Keung and Amay Bandodkar presented their research on advancing human stem cell-derived platforms for Angelman Syndrome at the 2022 FAST Science Summit. They discussed their work in engineering new models for Angelman Syndrome research and therapeutic testing using human stem cell models. They highlighted the importance of reflecting the diversity of Angelman Syndrome, using human models, and increasing research speed and throughput. The researchers also introduced their team of students who are actively involved in the research. They discussed specific projects related to large deletions, UPD and ICD, and the use of cerebral organoids for studying the effects of UBE3A absence. They also presented a scalable high-throughput multi-organoid screening platform for drug testing. The researchers expressed their gratitude to FAST for funding and emphasized the impact of their research in recruiting young scientists and attracting additional funding.

Introduction

In the 2022 FAST Science Summit, Dr. Albert Keung and Amay Bandodkar presented their work on advancing human stem cell-derived platforms for Angelman Syndrome research. Dr. Keung, an associate professor of chemical and biochemical engineering at North Carolina State University, focuses on using synthetic biology approaches to study and treat neuroepigenetic disorders. Dr. Bandodkar, an assistant professor in the Department of Electrical and Computer Engineering at NC State, combines electronics, material science, and biology to understand and develop new sensors and energy devices for studying organoids and drug testing.

The Importance of Student Involvement

Dr. Keung emphasized the importance of their students’ contributions and highlighted their hard work and dedication. The funding provided to their research goes towards supporting these students and nurturing the next generation of Angelman Syndrome researchers.

Reflecting the Diversity of Angelman Syndrome

The research groups led by Dr. Keung and Dr. Bandodkar are focused on addressing three key needs for experimental models in Angelman Syndrome research. The first need is to reflect the diversity of Angelman Syndrome, as different forms of the disorder may respond differently to therapeutics. To achieve this, the researchers are using molecular tools to edit human stem cells and create isogenic cell lines that mimic different forms of Angelman Syndrome. These isogenic cell lines help reduce variability between experiments and facilitate comparisons between researchers and institutions.

Creating Customizable Models

Dr. Begum Yagci, a chemical and biomolecular engineer, explained their approach to studying large deletions in Angelman Syndrome. They are using cell lines obtained from Angelman Syndrome individuals and adding back the genes that are lost in these individuals. To make the platform customizable and easily accessible to the Angelman Syndrome community, they are incorporating a “landing pad” into the cell lines. This landing pad provides a location for the genes of interest to integrate into the cell lines, allowing for the study of multiple genes simultaneously.

Modeling UPD and ICD Angelman Syndrome

Tyler Johnson, a chemical engineer, discussed their work on modeling Angelman Syndrome forms characterized by uniparental disomy (UPD) and imprinting center defects (ICD). They are using the landing pad technology and CRISPR-mediated epigenome editing to create cells that mimic UPD and ICD Angelman Syndrome. By studying these models, they aim to understand how these disruptions contribute to the disorder and identify potential therapeutic strategies.

Studying Human Neurons with Cerebral Organoids

Dr. Chris Estridge, a chemical and biomolecular engineer, explained their use of human cerebral organoids to study Angelman Syndrome. Cerebral organoids are 3D microtissues generated from stem cells that model human neurodevelopmental diseases. By applying single-cell RNA sequencing, they can analyze gene expression in individual cells and determine the effects of UBE3A absence and the surrounding genes on different cell types. This approach helps identify affected signaling pathways and cellular processes.

High-Throughput Drug Testing

Dr. Bandodkar discussed the need for high-throughput drug testing platforms to screen multiple drugs and therapeutics simultaneously. They are developing a scalable platform that uses thin and flexible sensors suspended in wells of a 96-well plate, where organoids are grown. These sensors can measure electrical and chemical signals from the organoids, allowing researchers to understand how the organoids respond to different drugs. The platform is designed to be easily integrated with existing technologies and can screen multiple samples continuously over a long period of time.

Conclusion

The research presented by Dr. Keung, Dr. Bandodkar, and their team aims to advance our understanding of Angelman Syndrome and accelerate the development of potential therapeutics. Their work focuses on creating diverse and customizable models, studying human neurons using cerebral organoids, and developing high-throughput drug testing platforms. The involvement of students in their research highlights the importance of nurturing the next generation of Angelman Syndrome researchers.