서울대학교 생물정보연구소와 생물정보학 협동과정 공동 주최로 특별 세미나를 아래와 같이 열고자 하오니, 많은 참여 바랍니다.

일시: 2016년 4월 6일 수요일 오전 11시

연사: 박한수 (이화여자대학교 자연과학대학)

장소: 서울대학교 25동 411호

Title: Genomic Medicine and Patient Derived Xenograft (PDX)

Abstract: Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Recent high-throughput analyses of genomic alterations reveal several driver genes and altered pathways in GC. However, therapeutic applications from genomic data are limited, largely due to the lack of druggable molecular targets and preclinical models for drug selection. To identify new therapeutic targets for GC, we performed array Comparative Genomic Hybridization (aCGH) of DNA from 103 GC patients for copy number alteration (CNA) analysis, and whole exome sequencing from 55 GC of the same patients for mutation profiling. Pathway analysis showed recurrent alterations in the Wnt signaling (APC, CTNNB1 and DLC1), ErbB signaling (ERBB2, PIK3CA and KRAS), and p53 signaling/apoptosis (TP53 and BCL2L1) pathways. In 18% of GC cases (19/103), amplification of the anti-apoptotic gene BCL2L1 was observed, and subsequently a BCL2L1 inhibitor was shown to markedly decrease cell viability in BCL2L1-amplified cell lines and in similarly altered patient-derived GC xenografts, especially when combined with other chemotherapeutic agents. In 11% of cases (6/55), mutations in DLC1 were found and also shown to confer a growth advantage for these cells via activation of Rho-ROCK signaling, rendering these cells more susceptible to a ROCK inhibitor. Taken together, our study implicates BCL2L1 and DLC1 as potential druggable targets for specific subsets of GC cases.

Education and Professional Career

Selected Publications

1. HansooPark, Sung-Yup Cho, Hyerim Kim, Deukchae Na, Jee Yun Han, Jeesoo Chae, Changho Park, Ok-Kyoung Park, Seoyeon Min, Jinjoo Kang, Boram Choi, Jimin Min, Yun-Suhk Suh, Seong-Ho Kong, Hyuk-Joon Lee, Edison Liu, Jong-Il Kim, Sunghoon Kim, Han-Kwang Yang, Charles Lee, et al. Genomic alterations in BCL2L1 and DLC1 contribute to drug sensitivity in gastric cancer. Proceedings of National Academy of Sciences. 2015; Published online before print September 23, 2015 | doi: 10.1073/pnas.1507491112

2. Dong-Sung Lee, Jong-Yeon Shin, Peter D. Tonge, Mira C. Puri, Seungbok Lee, HansooPark, et al. An epigenomic roadmap to induced pluripotency reveals DNA methylation as a reprogramming modulator. Nature communications. 2014;5:5619.

3. HansooPark, Dohoon Kim, Chun-Hyung Kim, Ryan E. Mills, Mi-Yoon Chang, Rebecca Cheryl Iskow, et al. Increased genomic integrity of an improved protein-based mouse induced pluripotent stem cell method compared with current viral-induced strategies. Stem cells translational medicine. 2014;3(5):599-609.

4. HansooPark, Hyun-Jin Kim, Seungbok Lee, Yun Joo Yoo, Young Seok Ju, Jung Eun Lee, et al. A family-based association study after genome-wide linkage analysis identified two genetic loci for renal function in a Mongolian population. Kidney international. 2013;83(2):285-92.

5. HansooPark,Seungbok Lee, Hyun-Jin Kim, Young Seok Ju, Jong-Yeon Shin, Dongwan Hong, et al. Comprehensive genomic analyses associate UGT8 variants with musical ability in a Mongolian population. Journal of medical genetics. 2012;49(12):747-52.

6. Young Seok Ju, Jong-Il Kim, Sheehyun Kim, Dongwan Hong HP, Jong-Yeon Shin, Seungbok Lee, HansooPark, et al. Extensive genomic and transcriptional diversity identified through massively parallel DNA and RNA sequencing of eighteen Korean individuals. Nature genetics. 2011;43(8):745-52.

7. Dongwan Hong, Sung-Soo Park, Young Seok Ju, Sheehyun Kim, Jong-Yeon Shin, Sujung Kim, HansooPark, et al. TIARA: a database for accurate analysis of multiple personal genomes based on cross-technology. Nucleic acids research. 2011;39(Database issue):D883-8.

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