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).
BS/MS: Tongji Medical University, Wuhan, China.
PhD: The Pennsylvania State University, State College, PA.
Fellowship: The Johns Hopkins University School of Medicine, Baltimore, MD.
Fellowship: University of Pennsylvania, Philadelphia, PA.
Developmental Biology
Modeling blood-brain barrier formation and cerebral cavernous malformations in human PSC-derived organoids. Cell Stem Cell. 2024; 31:818-833.e11.
Senktide blocks aberrant RTN3 interactome to retard memory decline and tau pathology in social isolated Alzheimer's disease mice. Protein and Cell. 2024; 15:261-284.
The interaction of Synapsin 2a and Synaptogyrin-3 regulates fear extinction in mice. The Journal of Clinical Investigation. 2024; 134.
Recalibrating the Why and Whom of Animal Models in Parkinson Disease: A Clinician's Perspective. Brain Sciences. 2024; 14.
A general design of pyridinium-based fluorescent probes for enhancing two-photon microscopy. Biosensors and Bioelectronics. 2023; 239:115604.
A 3D Microfluidic Device with Vertical Channels toward In Vitro Reconstruction of Blood-Brain Barrier. (2023) 2023:1-4.
Tau pathology epigenetically remodels the neuron-glial cross-talk in Alzheimer's disease. Science Advances. 2023; 9:eabq7105.
In preprints: humans, the new model organism. Development (Cambridge). 2022; 149.
Ultralong-Term Super-Resolution Tracking of Lysosomes in Brain Organoids by Near-Infrared Noble Metal Nanoclusters. ACS Materials Letters. 2022; 4:1565-1573.
Structural interaction between DISC1 and ATF4 underlying transcriptional and synaptic dysregulation in an iPSC model of mental disorders. Molecular Psychiatry. 2021; 26:1346-1360.
Ziyuan Guo, PhD5/20/2024