542회 정기세미나_차혁진 교수님(서울대)

생명과학연구소에서는 올해 정기세미나를 예전과 같이 매 달 한 번 목요일 오후 5시에 진행하기로 했습니다. 

2021년도 1학기 첫번째 정기세미나로 서울대학교 약학대학 차혁진 교수님을 초대하였습니다.  

세미나의 방식은 온라인 입니다.

일시: 2021년 3월 25일(목) 오후5시

온라인:https://kangwon-ac-kr.zoom.us/j/87324278442

(이루리의 공개된 자율강좌로 생명과학연구소 세미나를 찾아서 접속하셔도 됩니다.)

Pluripotent stem cell based GNE myopathy modeling

차혁진 교수(서울대학교 약학대학)

Despite the great potential of disease modeling with the isogenic pairs of human pluripotent stem cells (hPSCs), the extremely low efficiency of precise gene editing in hPSCs remains a technical hurdle for this approach. Herein, we took advantage of currently available base editors (BEs) to epitomize the isogenic disease model from hPSCs. Using this method, we established 14 hPSCs that harbor point mutations on the GNE gene, including four different mutations found in GNE myopathy patients. Due to lesser activation of p53 by BEs than Cas9, a higher editing efficiency with BEs was achieved. Four different mutations in the epimerase or kinase domains of GNE revealed mutation-specific hyposialylation, which was closely correlated to pathological clinical phenotypes. These mutation-specific hyposialylation patterns were evident in GNE protein structure modeling. Furthermore, treatment with a drug candidate currently under clinical trials showed a mutation-specific drug response in GNE myopathy disease models. These data suggest that isogenic disease models from hPSCs using BEs could serve as a useful tool for mimicking the pathophysiology of GNE myopathy and for predicting drug responses.

학력 및 약력

1993-1999   서울대학교 약학대학(B.S.)

1999-2004   University of Maryland, USA (Ph.D.)

2004-2007   National Cancer Institute, Harvard University, Georgetown University, USA (박사후연구원)

2007-2011   차의과대학교 (조교수)

2011-2018   서강대학교 생명과학과 (조교수, 부교수, 교수)

2018-현재   서울대학교 약학대학 (부교수)

주요발표논문 (최근)

1. Kwon OS, Kwon EJ, Kong HJ, Choi JY, Kim YJ, Lee EW, Kim W, Lee H, CHA HJ, Systematic dentification of a nuclear receptor-enriched predictive signature for erastin-induced ferroptosis, Redox Biol, 37, 101719

2. Go YH, Kim J, Jeong HC, Kim SM, Kim YJ, Park SJ, Moon SH, CHA HJ, Luteolin Induces Selective Cell Death of Human Pluripotent Stem Cells, Biomedicines, 8(11), 453

3. Choi JY, Lee H, Kwon EJ, Kwon OS, CHA HJ, TGFβ promotes YAP‐dependent AXL induction in mesenchymal‐type lung cancer cells, Mol. Oncol, 2020

4. Kong HJ, Kwon EJ, Kwon OS, Lee H, Choi JY, Kim YJ, Kim W, CHA HJ, Crosstalk between YAP and TGFβ regulates SERPINE1 expression in mesenchymal lung cancer cells, Int. J. Oncol, 58(1), 111-121

5. Kim KT, Park JC, Jang HK, Lee H, Park SW, Kim J, Kwon OS, Go YH, Kim W, Lee J, Bae S, CHA HJ, Safe scarless cassettefree selection of genome-edited human pluripotent stem cells using temporary drug resistance, Biomaterials, 262,120295 2020 Sep

6. Kwon OS, Lee H, Kong HJ, Kwon EJ, Park JE, Lee W, Kang S, Kim M, Kim W, CHA HJ, Connectivity Map-based drug repositioning of bortezomib to reverse the metastatic effect of GALNT14 in lung cancer, Oncogene 2020 Jun;39(23):4567-4580

7. Kwon OS, Lee H, Kim YJ, Cha HJ, Song NY, Lee MO, ERK Dephosphorylation through MKP1 Deacetylation by SIRT1 Attenuates RAS-Driven Tumorigenesis, Cancers 2020, 12, 909

8. Kim DH, Jang JH, Kwon OS, Cha HJ, Surh YJ Nrf2-induced reductive stress favours self-renewal of breast cancer stem-like cells via the FoxO3a-Bmi-1 axis, Antioxid. Redox Signal 2020 Jun;32(18):1313-1329