- Date: 16.04.2019
- Time: 11:30 am – 1:30 pm including lunch boxes
- Location: Embassy of Switzerland, 77 Songwol-gil, Jongno-gu, Seoul
- Participants : limited to 15-20 by registration order
- Free of charge but registration compulsory
- Registration and info:email@example.com
This month speakers
Prof. Seung Bum Park, Ph.D., FRSC
Director, CRI Center for Chemical Proteomics
Professor of Chemistry Department at Seoul National University, Seoul, Korea
Chair, Department of Biophysics and Chemical Biology, Seoul National University
Founder and CEO, Spark Biopharma, Inc.
Professor Seung Bum Park received his B.S. in chemistry and M.S. in organic chemistry at Yonsei University (Seoul, Korea). After completing his Ph.D. study at Texas A&M University, he was appointed as a HHMI Postdoctoral Research Fellow at Harvard University (with Prof. Stuart L. Schreiber). In 2004, he started his independent carrier as an Assistant Professor, and promoted to an Associate Professor with tenure (2008) in Chemistry Department at Seoul National University. Currently, he is a full professor and a Director of Center for Chemical Proteomics. In 2009, he spent his sabbatical as a visiting Professor at the Scripps Research Institute, San Diego, USA (with Prof. Peter Schultz). He also found bioventure company, Spark Biopharma, Inc. in 2016.
Prof. Orlando D. Schärer, Ph.D.
Associate Director, IBS Center for Genomic Integrity, Ulsan, Korea
Distinguished Professor, Ulsan National Institute of Science and Technology (UNIST), Korea
Orlando D. Schärer received a Diplom (MSc) from ETH Zürich (Switzerland), a PhD from Harvard University (USA) and did postdoctoral studies at Erasmus University (Netherlands). He held faculty positions at the University of Zürich, Switzerland (1999-2005) and Stony Brook University, NY, USA (2005-2016) before taking up his current positions in Ulsan, Korea, as Associate Director at the Center for Genomic Integrity of the Institute for Basic Science and Distinguished Professor of Life Sciences at UNIST. His research combines chemical and biological approaches to study DNA damage, DNA repair and DNA damage signaling pathways and their relationship to carcinogenesis and antitumor therapy.
FITGE-based Target Identification: New Tool in Chemical Biology
Seung Bum Park
Department of Chemistry, Seoul National University, Seoul 08826, Korea
The importance of molecular diversity has been clearly recognized to identify specific bioactive small molecules for the elucidation of mysterious biological processes. The diversity-oriented synthesis (DOS) was introduced for efficient population of molecular diversity in untapped chemical space using complexity-generating synthetic route. To maximize the molecular diversity with high relevance in biological space, we pursued privileged-substructure-based DOS (pDOS) strategy to emphasize the importance of maximized skeletal diversity through the creative reconstruction of core skeletons containing privileged substructures. The efficiency of hit discovery from pDOS libraries was envisioned due to their enhanced relevance to biological space. This is the first systematic study to demonstrate the importance of privileged structures for the construction of molecular diversity through a series of high-throughput screening processes and subsequent biological evaluations. Our divergent pDOS strategy can provide an efficient approach for the discovery of novel small-molecule modulators with excellent specificity in chemical biology and drug discovery. we developed a new target identification platform, FITGE, which aims to preserve protein-small molecule interactions under the intact cellular environment. After a series of failures using conventional target ID methods, we successfully identified the protein target of anti-proliferative compound with FITGE only under the live cell condition and observed the environment-dependent binding events of a functional small molecule by direct comparison between live cells and cell lysates. Even though it still requires the synthesis of bioactive probes with photo-crosslinker moiety, we believe our FITGE strategy can provide a unique technology platform for target identification in live cells.
References: Chem. Sci. 2019, 10, 3449–3458 (Front Cover); Curr. Opin. Chem. Biol. 2019 DOI: 10.1016/j.cbpa.2019.02.006; Chem. Sci. 2017, 8, 1127–1133; Nature Comm., 2016; 7: 13196; ACS Chemical Biology. 2016 11(1), 44–52; Angew. Chem. Int. Ed. 2012 51(22), 5447–5451  J. Am. Chem. Soc. 2016 138, 13630–13638.  J. Am. Chem. Soc., 2018, 140, 974–983 (Front Cover); Angew. Chem. Int. Ed. 2015 54(52), 15689–15693; Acc. Chem. Res. 2015, 48(3), 538–547  Chem. Sci. 2016 7, 5523–5529; Nat. Chem. Biol. 2014 10(12), 1055–1060.
DNA Repair Pathways: Guardians of the Genome and Targets for Antitumor Therapy
Orlando D. Schärer
Center for Genomic Integrity (CGI), Institute for Basic Science (IBS)
School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST)
The maintenance of genome stability is key to cellular survival and human health. Multiple DNA repair pathways are involved in surveying the genome for DNA damage caused by endogenous and exogenous damage to DNA. Most tumors harbor defects in one or more DNA repair pathways, which allows them to accumulate mutations in DNA that are associated with initial tumor formation as well as tumor progression by being able to select for tumor population that thrive in changing environments. These defects make tumors susceptible to treatment with DNA damaging agents such as cisplatin, and conversely, increased levels of DNA repair capacity are associated with resistance to treatment.
Our laboratory has been studying the interplay of DNA repair pathways and cancer therapy, with a particular focus on two pathways: nucleotide excision repair (NER) and interstrand crosslink (ICL) repair. Using mechanistic studies, we have shown how both of these pathways repair DNA lesions formed by antitumor agents, thereby contributing to chemoresistance. I will describe our progress toward understanding how the knowledge of DNA repair pathways as well as methods to measure DNA adducts levels in cells can be used to predict clinical outcomes and to match therapies with different tumor types.