Harvard Catalyst Profiles

Dr. Jaehong Suh studies the genetic and molecular mechanisms of Alzheimer’s disease (AD) and other neurodegenerative disorders, with the aim of identifying novel therapeutic targets and developing effective treatments for patients. Suh was involved in the identification of novel mutations from late-onset AD families in the prodomain of ADAM10, a major alpha-secretase that cleaves beta-amyloid (Abeta) region of amyloid precursor protein (APP). Subsequently, Suh and his colleagues generated a mouse model with the same mutations and showed that the ADAM10 mutations attenuate alpha-secretase activity of the enzyme, potentiate the accumulation of Abeta and decrease the generation of new neurons in the brain. Suh and his lab continue to characterize additional ADAM10 mutations, and identify novel ADAM10 substrates in the brain. Additionally, Suh is pursing mechanistic studies on another AD-associated gene, Ataxin-1, which was found recently in a genetic screen of AD families. Expansion of CAG trinucleotide repeat in Ataxin-1 gene is known to cause spinocerebellar ataxia type 1 (SCA1), a neurodegenerative disease that primarily impairs coordinated movement. At MGH, Suh has also studied the role of FE65 and FE65L1 APP-binding proteins on APP processing in neurons and identified abnormal eye and muscle phenotypes in the knockout mice for the two genes.