Topic: Alzheimer’s Disease: Translating Mechanism of Pathogenesis to Precision Medicine
Speaker: Professor Chen Xian, School of Medicine, University of North Carolina-Chapel Hill (UNC)
Date and time: April 11, 10:00–11:00
Venue: Auditorium, Y Building
Host: Shui Wenqing
Abstract:
By combining approaches including AD pathology-correlated chemoproteomics and proteomics, we discovered G9a-mediated translation regulatory mechanism of AD pathogenesis that defines the pathologies of AD. Accordingly, we developed a novel brain-penetrant inhibitor of G9a, MS1262, to block this G9a-regulated translation mechanism. Intermittent MS1262 treatment of multiple AD mouse models consistently restored both cognitive and noncognitive functions to healthy levels. Comparison of proteomic data of MS1262-treated AD mice with human AD patient data revealed that G9a regulates multiple pathological brain pathways that elaborate Aß plaque and neurofibrillary tangles, the hallmarks of AD progression. From these pathways, we identified MS1262-affected biomarkers of early-stage AD. This mouse-to-human conservation of G9a-regulated translation of AD suggests that the global, multifaceted restoration effects of MS1262 in mice could extend to relieve major symptoms of AD patients.
Biography:
Dr. Chen Xian is the Professor and Director of Technology Development at UNC Proteomic Center, and he is also the Founder of TransChromix Therapeutics. He has a long-standing interest in understanding the molecular pathways and mechanisms underlying autoinflammation-associated diseases such as cancer, sepsis, Alzheimer’s disease, and diabetes using his multi-disciplinary expertise. He has authored and co-authored more than 160 papers including some in Nature, Science, Cell, Nature Immunology, Cell Stem Cell, Molecular Cell, Immunity, Cancer Discovery, Nature Cancer, Science Advances, Nature Communications, etc. He also holds five patents and two US provisional patent applications for New Therapeutics for Alzheimer’s disease and COVID-19. His H-index is at 67 with 38613 citations.