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Jiayin Yang

Chief Technology Officer, Cell Inspire Pharma

Jiayin Yang is currently the Chief Technology Officer of Cell Inspire Pharma, a start-up company in Shenzhen, China that aims to develop candidate therapies for neurodegenerative diseases and rare diseases using stem cell-based models. He received his Ph.D. in stem cells and regenerative medicine from the University of Hong Kong. Dr. Yang has 12 years of research experiences in human pluripotent stem cells (PSCs) and genome editing with custom designed nucleases. In combination with these two cutting-edge technologies, Dr. Yang has generated a series of in vitro models with genome engineered induced pluripotent stem cells (iPSCs) for disease models and drug screening.


iPSC-Based High Throughput Platforms for Screening Novel Therapeutics for Treatment of Alzheimer's Disease and Parkinson’s Disease

Abstract

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are complex neurodegenerative diseases that affect millions of people worldwide and are currently no cure. Lacking of suitable cellular models and the inadequate diversity of the existing compound libraries are two hurdles for drug screening for both diseases. To overcome those limitations, we have created novel cellular models based on genetically modified and/or patient-derived human induced pluripotent stem cells (iPSCs). For AD cellular modeling, we site-specifically integrated AD-related genes at the AAVS1 site of a normal iPSC line and created two iPSC lines respectively. Neurons derived from both engineered lines displayed AD phenotypes in vitro, such as significantly elevated Aβ level and p-tau level compared to those of their isogenic parental line. For PD modeling, we obtained iPSC from a patient with young-onset PD (YOPD) who carried multiple mutations in both PARK2 and HTRA2 genes. Neurons derived from the YOPD iPSC displayed typical PD phenotype and severe neurodegenerative features. In order to create high throughput platforms suitable for drug screening, we have also established standardized processes for production of large quantities of uniform neurons from AD and PD iPSC lines and developed robust human neuron-based assays for drug candidate screening.

To test the suitability and robustness of our novel drug screening platforms, we have conducted a preliminary screening of more than one hundred natural chemical compounds plus some herb extracts derived from traditional Chinese medicines (TCM) in a 96-well plate format. Out of the samples screened, we identified more than 20 compounds that showed significant protection for neurons displaying AD and PD phenotypes. Among those 20 positive hits, 5 compounds also significantly downregulate Aβ42 level in the AD model. Our results indicate that combinations of suitable cellular models and the diversity of natural compounds derived from TCM offers a golden opportunity for development of novel therapeutics for treatment of AD and PD. This presentation will discuss details on the generation of our AD and PD cellular models, development of neuron-based assays and potential applications of those novel high throughput screening platforms.