Ziyuan Guo, PhD

The human brain is the most complex organ in the universe. While its unique characteristics allow us to think, abnormalities can lead to brain disorders, such as autism, schizophrenia and Alzheimer’s disease. Unfortunately, due to the inaccessibility of human primary tissue, scientists are limited in their study of disease etiology. This limitation significantly delays the advancement of new therapeutic developments.

As a neurobiologist and stem cell scientist, I’m interested in neurodevelopmental and neurodegenerative disorders, autism spectrum disorders, schizophrenia, Alzheimer’s disease, induced pluripotent stem cells (iPSCs), brain organoids, direct reprogramming, in vivo reprogramming, human neural development, human neural stem cells and glia-neuron interaction.

I draw on these interests — and my research experience — to develop a next generation “human nervous system in a petri dish” using cutting-edge stem cell technologies and engineering tools. To that end, my lab applies innovative stem cell technologies (including iPSCs, organoids and trans-differentiation) to study the etiology of neurodevelopmental and neurodegenerative disorders in the context of human genetics.

As lead author on an article published in Cell Stem Cell (Feb. 2014), I was among the first to report direct reprogramming of reactive glial cells into functional neurons in adult mouse brains. We accomplished this by overexpressing a single neural transcriptional factor (NeuroD1).

This study — which was named one of the best of 2014 by Cell Stem Cell — propelled us in a new direction of utilizing an in vivo reprogramming approach to treating neurological and neurodegenerative disorders. We first published synaptic dysfunction in a human iPSC model of mental disorders carrying a mutation disruption in schizophrenia 1 (DISC1) in the journal Nature (Nov. 2014). These efforts shed light on using human iPSCs to model and study neurodevelopmental disorders, such as schizophrenia.

I’ve received several professional awards and honors. This recognition includes a Trustee Award from Cincinnati Children’s (2020-2022), a postdoctoral fellowship award from the Maryland Stem Cell Research Fund (2016-2018), an Alumni Association Dissertation Award from Penn State University (2015), and a J. Ben and Helen D. Hill Memorial Fund Award, also from Penn State University (2012-2013).