The Revolutionary Alzheimer’s Disease Research at Yonsei University: A look inside Professor YoungSoo Kim’s laboratory

Professor YoungSoo Kim of Underwood International College’s Bio-Convergence Major has been doing revolutionary research in the Alzheimer’s disease field. Professor Kim uses animal models to simulate the Alzheimer’s disease to find drug candidates and biomarkers that can indicate the presence of Alzheimer’s disease early on in the development of the disease. The research that Professor Kim does is interdisciplinary, as it combines various disciplines of natural sciences including organic chemistry, chemical neurobiology and biochemistry. Professor Kim’s laboratory uses solid-phase peptide synthesis, protein-based in vitro assays, HTS drug screening, and in vitro animal studies. 

Alzheimer’s disease is characterized by memory loss and cognitive deficits. The pathophysiology of Alzheimer’s disease is the formation of two types of brain lesions. These brain lesions are senile plaques and neurofibrillary fibers. The formation of the brain lesions occurs years prior to the presence of clinical symptoms. Thus, it is imperative to find early detection tools. In terms of Alzheimer’s disease therapeutics, Professor Kim’s laboratory is working on finding drug targets to alleviate the symptoms of the neurodegenerative disease.

Professor Kim’s research is largely divided into three categories – drug discovery, diagnostic methods and methodology development. In drug discovery, a key molecule that Professor Kim’s team found was 4-(2-hydroxyethyl)-1-piperazinepropanesulphonic acid (EPPS). EPPS can break down neurotoxic plaques of amyloid-β (Aβ) that form during Alzheimer’s disease development. The disaggregation of Aβ plaques mitigated symptoms of cognitive deficits and memory loss in mice models. An important implication of EPPS’s ability to reduce the level of behavioral deficits in mice is that the formation of Aβ plaques is a crucial factor of Alzheimer’s disease progression. 

In diagnostic methods, Professor Kim’s laboratory developed a blood test that can detect Alzheimer’s disease. Amyloid-β (Aβ) protein is strongly correlated with the onset of Alzheimer’s disease. Aβ is a biomarker that is able to cross the blood-brain barrier. EPPS can be used to separate Aβ aggregates into monomers and this can be quantified. While the direct causation of Alzheimer’s disease as Aβ aggregates is not fully confirmed, there is a strong correlation with the concentration of Aβ and Alzheimer’s disease development. It is critical that other biomarkers are investigated to use in conjunction with Aβ to further corroborate the blood test results for the accurate diagnosis of Alzheimer’s disease.

Finally, in methodology development Professor Kim outlines the ways in which Alzheimer’s disease mice models can be prepared. An acute mouse model can be made by directly injecting Aβ into the intracerebroventricular injection. In addition, Professor Kim developed a method to efficiently synthesize Aβ. 

Professor Kim was highly successful in identifying key drug targets, diagnostic methods and the necessary protocol to develop mice models to study the brain. This does not mean that he did not face any obstacles. First, as Professor Kim is not a medical doctor, he is not able to perform his own clinical trials. This means that translational research is often difficult. However, Professor Kim is able to collaborate with Sinchon Severance’s neurology department in order to further study the effects of his research. Second, Alzheimer’s Disease’s main risk factor is aging. This means that the research needs time for cells and mice to age. It may take months and even years for the mice models to show behavioral deficits. Thus, it is imperative to plan ahead to age the mice to test for certain drug targets. Third, administering drugs in animal testing requires many mice models of the same gender, age and Alzheimer’s disease progression. There needs to be both positive and negative controls, as well as the mice tested with the drug targets. Approximately a hundred mice may be required for a test using a single drug target. 

Finally, Professor Kim gave valuable advice for UIC students interested in going to graduate school. It is very important to have laboratory experience, especially as an undergraduate student. Working at a lab shows a good representative of life as a graduate student. In addition, students can interact with graduate students and get a first-hand experience of conducting their own research. 

Currently, Professor Kim is working with undergraduate and graduate students from UIC and the school of pharmacy. He is organizing a remodeling of the laboratory research area to accommodate behavioral studies in mice. Professor Kim is hoping to conduct more studies to further elucidate the mechanisms of Alzheimer’s disease and to find more drug targets for therapeutic effects.

In the picture of undergraduate students, their names are (clockwise from top left)
Seungwoo HONG (BC ‘17)
Soljee YOON (Ewha Univ. Senior)
Hyung Ji LEE (BC ‘18)
Dakyung LEE (BC ‘16)
Sohee PARK (BC '16, Integrated BS/MS degree in Pharmacy) 
Heeyang LEE (BC ‘16, Integrated BS/MS degree in Pharmacy)
Prof. YoungSoo Kim
Daniella UGAY (LSBT ‘16)