One of the major focuses in the neuroscience field is to understand the pathogenic mechanisms underlying neurological and neurodegenerative diseases, which afflict millions of people worldwide. However, no effective therapeutic interventions have been developed to date. This is partially attributed to our limited knowledge of the molecular mechanisms underlying these debilitating disorders. In the JiaLab at Tsinghua, we aim to investigate the pathogenic mechanisms of and advance therapeutic-target discovery for neurodegenerative and neurodevelopmental diseases.
Our main approaches to achieve these goals include animal models of disease using chemical-induced mutant mice, such as mutagen ENU (N-ethyl-N-nitrosourea)-induced mutants. These disease models recapitulate the vital pathological mechanisms
of neurodegenerative and neurodevelopmental phenotypes. Intriguingly, mice share over 90% gene similarity with humans. The identification of disease mutant genes in mice has significantly deepened our insights into the disease mechanisms. Furthermore, what we have discovered about disease-causing and/or disease-modifying genes will enhance our understanding of their physiological functions in the brain.
Our group employs ENU-induced mutagenesis and screens for new genes or modifiers involved in neurological or neurodegenerative phenotypes. Our current research focuses include:
(1) Investigating the disease mechanisms underlying neurodegenerative and neurodevelopmental disorders resulting from RNA metabolism abnormalities and the dysregulation of ER homeostasis.
(2) Exploring molecular mechanisms underlying mammal vocalization and their dysfunctions in neurodevelopmental disorders.
(3) Developing novel cell and animal models for neurological and neurodegenerative diseases.