Assistant Professor of Neurology, Harvard Medical School; Assistant in Neurology, Genetics and Aging Research Unit, Massachusetts General Institute for Neurodegenerative Diseases, Department of Neurology, Massachusetts General Hospital
Dr. Kim has been studying pathogenic mechanisms of Alzheimer’s disease (AD) for more than 16 years. He and his team investigated physiological and pathological functions of BACE1 and presenilin/gamma secretase, two key enzymes that regulate generation of amyloid beta, a major pathogenic molecule associated with AD. Dr. Kim and his colleagues characterized four novel presenilin/gamma secretase substrate proteins and BACE1 substrate proteins that explain how BACE1 regulates neuronal activity under physiological conditions (Kim et al., Nat. Cell. Biol., 2007). Excessive amounts of BACE can disrupt the neuronal activity, making nerve cells more vulnerable to aberrant firing and perhaps seizures, which may explain the higher risk of seizures in Alzheimer’s patients. Recently, Dr. Kim’s lab, together with Dr. Rudy Tanzi’s, developed an innovative three-dimensional (3D) human stem cell culture model of AD (Choi et al., Nat., 2014). By cultivating genetically modified human neural stem cells in a 3D gel system, they were able to recapitulate key events of AD pathology, including amyloid beta plaques and neurofibrillary tangles (NFTs) for the first time. This unique human neural cell culture model can be used for large-scale, high-throughput screening for novel therapeutic targets, which is not feasible in the current AD mouse models. Kim’s “Alzheimer’s in a Dish” model has been listed as one of “10 Breakthrough Technologies of 2015” by “MIT Technology Review,” and it also won the 2015 Smithsonian American Ingenuity Award (Drs. Kim and Tanzi).