My research focuses on the development of therapeutics and diagnostics of Alzheimer’s disease (AD) based on pathological interpretation of the mystery of the disorder. Such research interests led us to develop and commercialize blood tests and multiple drug candidates for AD. AD is the most common and fatal neurodegenerative disorder with catastrophic effects on the elderly population. Typical symptoms of AD are progressive memory loss, cognitive impairment, and behavior disorders to death. The cause of AD is not clearly understood yet due to insufficient information about the etiology and pathogenesis of selective neuronal cell death.

In our lab, we study the disease cascade and biomarkers to look for AD therapeutics and diagnosis probes via customized peptide synthesis, protein-based in vitro assays, HTS drug screening and in vivo animal studies. There is no single test that can show whether a person has AD. While physicians can almost always determine if a person has dementia, it may be difficult to determine the exact cause. Diagnosing Alzheimer's requires careful medical evaluation such as Brain Imaging and Blood Test. However, current early diagnosis of AD only depends on MMSE (mini-mental state examination), which lacks accuracy and only determines level of dementia, not AD. So far, I have equipped and trained my lab to perform AD research from A to Z. As drug discovery often requires interdisciplinary investigations, my team is fully functional in bioorganic protein chemistry, high-throughput drug screening, learning and memory behavioral studies, and neuropathological investigations based on chemical neurobiology. Using this infrastructure, I have published 70 peer-reviewed science articles, 35 registered thirty domestic and international patents, and licensed out 6 technologies for commercialization.

  Based on the belief that research of Alzheimer’s disease must combine the investigation of mechanism, development of diagnostic method, and development of new drug concurrently in order to derive at a mutually helpful result and create a synergy effect, our lab is conducting a research on these three parts in parallel.  A study aggregating the relevant key infrastructure of our lab was recently published in Angewandte Chemie International Edition (IF 12.257).  From its title, ‘Discovery of chemicals to either clear or indicate amyloid aggregates by targeting memory‐impairing anti‐parallel Aβ dimers’ (doi: 10.1002/anie.202002574), the content of the research is relatively large.  To summarize briefly, the study revealed that only the anti-parallel dimer structure among Aβ protein plaques causes Alzheimer’s disease, developed an efficacy study system to develop a fluorescent brain image probe, which can selectively target anti-parallel dimer, and derived at a drug that can eliminate amyloid aggregator from the brain of transgenic mouse like a new drug using drug repositioning approach.

  At first, we were simply curious about the mechanism, and intended to examine the difference in pathological roles based on two structures of dimer, but since our result of ‘this is how parallel dimer and anti-parallel dimer are different’ led to so many responses of ‘so what?’, we decided to design an efficacy study system.  After designing an efficacy study system, it was meaningless without verifying the medical effect, so we obtained FDA-approved drug library and performed screening, and a few drugs corresponded luckily.  When we submitted the manuscript containing the result of drug search, we were rejected with the opinion that ‘shouldn’t you verify the efficacy in an animal model?” so we proceeded to the animal experiment.  The editor of the journal who rejected it and the reviewer must have liked it because it was accepted and was published as the ‘Hot Paper’ (when 2 or more reviewers consider it significant).  This process took exactly 19 years.  My goal has been upgraded multiple times, and the subject of research was vague that I wasn’t sure whether it should have been focused on the fundamentals, diagnosis, or new drug, so I have been conducting the research with spare reagents and spare time for a long time.

  There still are many ‘unfunded projects’ being conducted in the lab.  In addition, there is another ‘Long-term 3-part Alzheimer’s disease research’ that has been conducted for over 10 years, and I was accepted for POSCO Science Fellowship (11th term) last year with this research subject.  This study investigates the protein accumulation mechanism in Alzheimer’s disease and develops new drug and diagnostic technique, and has recently completed investigation in the brain tissue of Alzheimer’s disease patient.  In case of anti-parallel dimer that was published this year, it has to proceed to the next step by setting different steps of milestones and verifying them, but it is very difficult to obtain research funds with a research subject that is too absurd or challenging just with a hypothesis.  I have applied multiple times with the identical subject, but bitterly realized as I failed in the document screening process.  I deeply appreciate POSCO TJ Park Foundation for giving me the opportunity to pursue this challenging research.  When I first heard about POSCO Science Fellowship in 2010, it seemed too far for me to apply, but it is a great honor to be selected as the fellow of the year 10 years later, and based on this opportunity, I would like to continue more challenging researches and aim for POSCO TJ Park Prize in the future.  I hope that POSCO Science Fellowship will bring the opportunities of challenge to many more fellow scientists, and in order to do so, I believe the previous fellows must bring honor to the fellowship, which I will do so by devoting myself to research.