Breast – Functional Proteomics Center, Korea Institute of Science and Technology (Coordinating Center)

Brief Description of Project:

Proteomics has been considered a revolutionizing technology for discovering phenotype-based biomarkers, that is, protein biomarkers, and tremendous development has been achieved recently in proteome separation and mass analysis. However, the current proteomics technology of analyzing the whole proteome including PTM (post-translational modification) in a quantitative manner is far from perfection. We established a national core-facility network to maximize our limited resources, and have focused on establishment of high-throughput platform for proteome analysis. This strategy of networking allows us to share individual expertise in specific areas and to become a competitive team as a whole.

Our common platform is LC-based proteome separation (capillary LC and multi-dimensional LC) and enrichment by various capturing methods prior to LC separation. We focus on differential and quantitative analysis as well as on PTM analysis. In the informatics area, we want to develop (or adopt) an integrative platform where data processing, storage, and retrieving are seamless and fast. We also focus on algorithm development for PTM analysis. In proteome analysis, we focus on development of high-information analytical tools by combining high resolution online separation and advanced mass spectrometric techniques. We also are interested in developing isotope-coded labeling reagents, such as ICenS, for quantitative analysis. Regarding the cancer subjects, we focus on breast and colon cancers because these cancers have a higher growth rate of recent incidence in Korea than other cancers.

We joined the International Consortium to overcome current technology barriers in the field by sharing informatics, reagents, and analytical tools developed in each member teams.

Team Members and Expertise:

Jin Woo KIM, M.D., Ph.D. (The Catholic University of Korea, Kangnam St. Mary's Hospital) [jinwoo@catholic.ac.kr]
Dr. Kim is a professor of Department of Obstetrics & Gynecology, Kangnam St. Mary's Hospital, College of Medicine, The Catholic University of Korea. His major is a gynecologic oncologist. He is also in charge of 'Research Institute of Medical Science', College of Medicine, The Catholic University of Korea. Prof. Kim has been working on disease-related genes/proteins identification, monoclonal antibody development and transgenic animal model production. He is also working as an Adjunct Associate Professor of Department of Immunology & Microbiology, New York Medical College, Valhalla, New York and Active Member of American Association of Cancer Research. His work has earned him numerous international awards including Yu Han Medical Award and Smith-Klein Award.

Cheolju LEE, Ph.D. (KIST) [clee270@kist.re.kr]
Dr. Lee joined Korea Institute of Science and Technology (KIST) in 2002 and has been working in proteomics research field as a senior research scientist. He received his Ph.D. degree in Biophysics from Seoul National University in 1997 and worked as a postdoctoral fellow at the Northwestern University and Korea Research Institute of Bioscience and Biotechnology. During this period, he was trained for the study of protein folding/unfolding, protein crystallography, enzyme kinetics, etc. Since joining KIST, he has also been trained for mass spectrometry, and participated in the settlement of proteomics technology infra in KIST. This includes LCQ DecaXP Plus ion trap mass spectrometer equipped with Agilent 1100 series capillary LC, and 4700 Proteomics Discovery MALDI-TOF/TOF mass spectrometer equipped with mHPLC and Shimadzu AccuSpot microspotting system. Currently he works in various fields of proteomics with those mass instruments. His ongoing projects are as follows: 1) Method development of quantitative proteomics and its application to biomarker discovery in human breast and colon cancer; 2) Purification and identification by affinity chromatography and mass spectrometry of receptor proteins binding to immune-modulating peptides; 3) Rapid kinetics for oxidation-reduction reaction of redox-regulated proteins using mass spectrometers.

Kong-Joo LEE, Ph.D. (Ewha Womans University) [kjl@ewha.ac.kr]
Dr. Kong-Joo Lee received her graduate training in Chemistry at the Stanford Unversity(1986) and post-doctorial training in Cancer Biology at Stanford Medical School(1998). Since she returned to Korea, she combine the analytical tools (capillary electrophoresis, GC-MS, LC-MS. MALDI-TOF MS and ESI-q-TOF tandem MS) to understand the protein regulation in signaling processes, which underlie many biological processes and help define the causes aging and various diseases. She is a manager of Ewha Proteomics Center , one of finest proteomic center in Korea and is on the Editorial Board of f the Journal Molecular & Cellular Proteomics (MCP, ASBMB), from 2002. She employed cutting edge technologies (e. g. proteomics using mass spectrometry, bioinformatics and biological study) to define the functional regulations of proteins involved in stress-related signaling pathways. Her proteomics research helped develop a web-based repository of the signaling pathways known as ROSPath and provide a means for managing data produced by large scale and high-throughput proteomics. She serves as a Dean of the Division of Molecular Life Sciences, Ewha Womans University, for six years (1998-2005) and a Dean of Research Affairs and University-Industry Collaboration Foundation (2005-2006).

Sang-Won LEE, Ph.D. (Korea University) [sw_lee@korea.ac.kr]
Dr. Sang-Won Lee is an assistant professor at the Korea University, Seoul, Korea and has expertise with mass spectrometry and separation science that ranges from design of new instrumentation to its application in biological research. Dr. Lee carried out his post-doctoral research at the Pacific Northwest National Laboratory (PNNL), Richland, Washington in Richard D. Smith's laboratory. He has been appointed to a faculty member at the Korea University since 2002, and his current researches include the development and application of advance proteomics technology based on ultra-high pressure liquid chromatography and high performance mass spectrometry. He is also interested in developing novel chemical methodologies to sensitively and dynamically analyze protein complexes. Dr. Lee received his Ph.D. degree in Physical Chemistry at the California Institute of Technology in 2000.

Dong-Young NOH, M.D., Ph.D. (Seoul National University Hospital) [dynoh@plaza.snu.ac.kr]
The research teams in the program are to focus on discovery of Biomarkers for early detection of Breast cancer and chemotherapy resistance as well as establishment of breast cancer mouse model for proteomic analysis, which will be followed by studies on protein networks and disease mechanisms. Dr. Noh has collected many breast cancer and normal tissues, blood samples since 1995.

Eunok PAEK, Ph.D. (University of Seoul) [paek@uos.ac.kr]
Dr. Paek joined University of Seoul as a faculty member in September 2001, and she embarked on a research project that aims to build a database for cell signaling pathways. In this project, she proposed an innovative way to model cell signaling pathways by representing them at multiple layers of abstraction. Based on this model, a web-based database has been developed and put into operation. She has also designed and developed various software tools that can be used for proteome research such as sequence pattern search and discovery, and pathway visualizer and editor. This project has led her attention towards informatics for proteomics and one of her recent research interests includes developing algorithms that can effectively interpret tandem mass spectra to identify peptides and their modifications. Dr. Paek received her Ph. D. in Computer Science at Stanford University (1991) and had working on various problems in the field of Artificial Intelligence, especially that of natural language processing, knowledge representation and reasoning, and intelligent user interfaces, both in academia and industrial research organization.

Zeeyong PARK, Ph.D. (GIST) Zee-Yong Park [zeeyong@gist.ac.kr]
Dr. Zee-Yong Park is currently an assistant professor in the department of life science at Gwangju Institute of Science & Technology. He leads the laboratory for biological and proteomic mass spectrometry. The biological and proteomic mass spectrometry lab is running two LC-MS/MS (Thermo's LCQ & LTQ) and Sequest cluster server (14 nodes) to develop new proteomic techniques for large-scale quantitative analysis of posttranslational modifications and protein profilings. Its research efforts include improving peptide separation capability of current multidimensional LC techniques, developing new types of capillary LC peptide separation techniques, and enhancing ionization efficiencies of posttranslationally modified peptides with chemical and non-chemical approaches. Dr. Park received his Ph.D. degree (Chemistry) from Texas A&M University in 2001, under the guidance of Dr. David H. Russell. Then he did his postdoctoral training with a well-known protein mass spectrometrist, Dr. John R. Yates III at the Scripps Research Institute for 2 years. Since he got a faculty position right after the postdoctoral training, he has been actively working on a large scale proteome analysis using shotgun proteomics approach and planning to expand the applicabilities of shotgun proteomics approach in the area of cancer biomarker discovery.

Incheol SHIN, Ph.D. (Hanyang University) [incheol@hanyang.ac.kr]
Dr. Incheol Shin received his Ph.D. in biological science from Korea Advanced Institute of Science and Technology (KAIST) in 1996. After working as a post-doc and a research faculty in Korea Basic Science Institute and Hanyang University during his military duty period, he moved to Vanderbilt Ingram Cancer Center in Nashville, TN and worked there for 3 years as a post-doc and 2 years as a research faculty. Under the guidance of Dr. Carlos Arteaga, a director of Breast Cancer Research Program and Breast SPORE program, he has been working on both in vitro and in vivo models of breast cancer using cultured cancer cells and transgenic mouse lines. He has shown that phosphorylation of cdk inhibitor, p27 on Thr157 residue by Akt could be a prognostic marker for breast cancer. In collaboration with Dr. Arteaga, he is currently developing a single chain recombinant antibody against Thr157 phosphorylated p27 for a potential prognostic use. In March 2005, he returned to Korea to work as an assistant professor at the department of life science in Hanyang University.

Myeong-Hee YU, Ph.D. (Functional Proteomics Center-Biomarker Team PI) [mhyu@kist.re.kr]
In July of 2002, Dr. Yu took responsibility in managing Functional Proteomics Center, one of 21C Frontier R&D Initiatives of Korean Ministry of Science and Technology. The Center's goal is to establish infrastructure of proteomics core technology in Korea with a mission identifying novel biomarkers and therapeutic target proteins for human diseases. The research teams in the program are to focus on technology development for proteome separation and identification, as well as on proteomic analysis of samples from disease models and appropriate patients, which will be followed by studies on protein networks and disease mechanisms. Dr. Yu received Ph.D. at the University of California, Berkeley (1981) and did postdoctoral training at M. I. T. (1982-1985). Dr. Yu has been working on problems of folding and stability for over 20years. She has shown that genetic emphysema, a human disorder resulting from alpha-1-antitrypsin deficiency, is associated with a hepatic block in the folding process, linked to a kinetic anomaly in the secretion process of this protein. Her work has earned her numerous national and international awards including UNESCO-L'Oreal Award from UESCO (1998), Seoul City Cultural Award from Seoul City (2001), and Order of Science and Technology, Ungbi Medal, from Korean Government (2004). She has been a member of the Korean National Academy of Science and Technology since 2002.