UMass Researcher Receives Trailblazer Award from National Institutes of Health

Guangyu Xu

College of Engineering researcher, Guangyu Xu, associate professor of electrical and computer engineering and adjunct associate professor of biomedical engineering, has received the National Institutes of Health (NIH) Trailblazer Award, $598,136 over three years, to pursue his research on dissecting inter-region communication in human organoid models with dual-color optogenetic probes. These probes will use micro-LED based light to control cell activity at high spatiotemporal resolutions. Xu's findings will advance our understanding of neurological conditions such as schizophrenia, autism spectrum disorders, Parkinson's disease and epilepsy.<_o3a_p>

The NIH Trailblazer Award program supports new and early-stage investigators pursuing research bridging engineering and the physical sciences with the life and/or biomedical sciences. A Trailblazer project may be exploratory, developmental or high-risk/high impact.<_o3a_p>

Xu, with his co-investigators Yubing Sun, associate professor of mechanical and industrial engineering, and ChangHui Pak, assistant professor of biochemistry and molecular biology, will establish an optogenetic organoid probing system to dissect inter-regional communication at cellular precision, comparatively tested in organoid disease models and their control groups.<_o3a_p>

This research will leverage Xu's latest development of dual-color optoelectronic neural probes, which can both excite or suppress electrical activities within the same neuron, as opposed to single-color probes which can only control brain activity in one direction.<_o3a_p>

Xu's research has two scientific aims: optogenetic probing of region-specific, depth-dependent organoid dynamics and inter-regional communication within living organoids.<_o3a_p>

He plans to achieve this by creating probes that can reach various depths and regions of the organoid tissue. One of them will integrate approximately 20 groups of dual-color LEDs and microelectrodes in a one-millimeter span, being only about a quarter of a millimeter thick and 50 micrometers wide, about the width of a human hair. The other will contain two to four identical shank structures being placed one to three millimeters apart from each other.<_o3a_p>

The team plans to demonstrate their technology using human organoid models of schizophrenia - a condition related to disordered communication between different parts of the organoid tissues. These tissues are stem-cell-derived three-dimensional (3D) cultures that can mimic targeted human organs, lending themselves to remarkable basic research and clinical applications. Their team is well versed for organoid culture, characterization and preparation for optogenetics studies.<_o3a_p>

"To model specific neurodevelopmental disorders, people should look into how different sub-regions of the brain are talking to each other," Xu explains. "You would benefit from simultaneously poking and recording cell activities from different functional regions in these human-specific tissues at cellular precision. Furthermore, we might be able to identify some very disease-specific phenotypes in terms of how these regions talk to each other."<_o3a_p>

Such capability could advance the development of various organoid disease models such as autism spectrum disorders, Parkinson's disease and epilepsy, since there is a growing consensus that these diseases are a result of disordered cellular circuits.<_o3a_p>

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