Mechanism of neurodegeneration using biochemistry guided by human genetics.

Seong laboratory is focused on understanding the fundamental mechanism of neurodegenerative diseases and neurodevelopmental disorders using precise genetic disease cells/mice models. Our research into the structural, biochemical, and functional properties of the full-length huntingtin protein continues to aim to understand Huntington’s disease (HD) at its root cause. We have also expanded our research to investigate several strong candidate genes as a HD genetic modifier suggested from the genome-wide association study with HD patients. Our application of biochemistry guided by human genetics will continue to elucidate the fundamental causes of disease while suggesting routes for mechanism-based treatments.

1. Structural and functional study of mutant huntingtin is to understand the effects of polyglutamine expansion on full-length huntingtin structure and function as the primary cause in HD.
2. Using loss-of-function mutations in HTT underlie LOMARS, a severe recessive neurodevelopmental condition, we aim to understand huntingtin normal function, how reduced levels lead to abnormal development and how much is needed to maintain adult neurons.
3. We have developed biochemical genetic approaches to identify modifier genes from genomic regions implicated by genome-wide significant polymorphism associations.
4. CDKL5 project is to determine the biology of CDKL5’s two kinase isoforms including identifying their novel substrates and characterize CDKL5 Deficiency Disorder patient iPSC/NPC/differentiated neurons.