암연구소 소개

연구실 소개

방사선반응관련 세포신호전달계 및 종양면역 연구실

Laboratory of Cell Signaling and Tumor Immunology implicated in Radiation Response
본 연구실은 수년간 암세포의 생존 관련 세포신호전달계의 효율적인 제어를 통해 방사선 저항성을 극복하려는 치료전략에 대한 전임상연구를 통해 이를 임상시험으로 이행하는 연구를 수행하여 왔다. 최근에는 방사선 및 면역억제세포를 표적으로 하는 다양한 약제를 병합하여 면역관문억제제의 치료 저항성을 극복하는 전략에 대한 이행성연구 및 임상적으로 유용한 바이오마커를 발굴하고자 면역유전체 연구에 집중하고 있다.
연구진은 책임연구자인 김인아 교수, 장범섭 교수, 위찬우 교수, 강미현 연구원, 장원익, 송준영, 김민지, 한민국, 김민지 학위생들로 구성되어 있다.
참여 연구원
김인아

김인아 교수

  • 소속 : 방사선종양학교실
  • 전공 : 뇌종양 유방암
  • 메일 : inah228@snu.ac.kr
연구내용

논문
PI3Kγδ inhibitor plus radiation enhances the antitumor immune effect of PD-1 blockade in syngenic murine breast cancer and humanized patient-derived xenograft model. Min Guk Han, Bum-Sup Jang, Mi Hyun Kang, Deukchae Na, In Ah Kim. European Journal of Cancer 2021; 157:450-463.  
PI3Kalphaδ inhibitor combined with radiation enhances the antitumor immune effect of anti-PD1 in a       syngeneic murine triple negative breast cancer model. Jang WI, Han MK, Kang MH, Park JM, Kim EE, Bae JY, Ahn S, Kim IA.  Int J Radiat Oncol Biol Phys 2021; 110(3):845-858  
Tumor mutation burden, immune checkpoint crosstalk and radiosensitivity in single-cell RNA           sequencing data of breast cancer. Jang BS, Han W, Kim IA. Radiother Oncol. 2020:142:202-209
A radiosensitivity gene signature and PD-L1 status predict clinical outcome of patients with glioblastoma multiforme in The Cancer Genome Atlas Dataset. Jang BS, Kim IA. Cancer Res Treat 2019:52(2):335-354
A radiosensitivity gene signature and PD-L1 predict the clinical outcomes of patients with lower grade glioma in TCGA. Jang BS, Kim IA. Radiother Oncol. 2018;128(2):245-253. 
Inhibition of PI4K IIIα radiosensitizes in human tumor xenograft and immune-competent syngeneic murine tumor model. Park Y, Park JM, Kim DH, Kwon J, Kim IA. Oncotarget 2017; 30;8(66):110392-110405
A radiosensitivity gene signature and PD-L1 status predict clinical outcome of patients with invasive breast carcinoma in The Cancer Genome Atlas (TCGA) dataset. Jang BS, Kim IA. Radiother Oncol 2017; 124:403-407
Targeting phosphatidylinositol 4-kinase IIIα for radiosensitization: a potential model of drug repositioning using anti-HCV agent. Kwon J, Kim DH, Park JM, Park YH, Hwang YH, Wu HG, Shin KH, Kim IA.  Int J Radiat Oncol Biol Phys 2016; 96:867-876
MicroRNA-200c increases radiosensitivity of human cancer cells with activated EGFR-associated      signaling.  Koo T, Cho. BJ, Kim DH, Park JM, Choi EJ, Kim HH, Lee DJ and Kim IA.  Oncotarget 2017;8(39): 65457-65468 
Radiosensitizing effect of lapatinib in human epidermal growth factor receptor 2-positive breast cancer cells. Yu T, Cho BJ, Choi EJ, Park JM, Kim DH, Kim IA. Oncotarget 2016;7(48): 79089-79100 
Inhibition of STAT3 enhances the radiosensitizing effect of temozolomide in glioblastoma cells in vitro and in vivo. Han TJ, Cho BJ, Choi EJ, Kim DH, Song SH, Paek SH, Kim IA. J Neurooncol. 2016;130(1):89-98
MicroRNA-203 modulates the radiation sensitivity of human malignant glioma cells. Chang JH, Hwang YH, Lee DJ, Kim DH, Park JM, Wu HG, Kim IA. Int J Radiat Oncol Biol Phys. 2016;94(2):412-20. 
Isotype-Specific Inhibition of Histone Deacetylases: Identification of Optimal Targets for Radiosensitization. Kim JH, Moon SH, No M, Kim JJ, Choi EJ, Cho BJ, Kim JS, Kim IH, Kim IA. Cancer Res Treat 2016;48(3):1130-40
The effect of chemoradiotherapy with SRC tyrosine kinase inhibitor, PP2 and Temozolomide on malignant glioma cells in vitro and in vivo. Eom KY, Cho BJ, Choi EJ, Kim JH, Chie EK, Wu HG, Kim IH, Paek SH, Kim JS, Kim IA. Cancer Res Treat 2016;48(2):687-97
Radiosensitization with combined use of olaparib and PI-103 in triple-negative breast cancer, Jang NY, Kim DH, Cho BJ, Choi EJ, Lee JS, Wu HG, Chie EK, Kim IA. BMC Cancer 2015;15:89 
Enhanced cytotoxic effect of radiation and temozolomide in malignant glioma cells: targeting PI3K-AKT-mTOR signaling, HSP90 and histone deacetylases. Choi EJ, Cho BJ, Lee DJ, Hwang YH, Chun SH, Kim HH, Kim IA. BMC Cancer. 2014 ;13;14-17
MicroRNA-7 increases radiosensitivity of human cancer cells with activated EGFR-associated signaling. Lee KM, Choi EJ, Kim IA. Radiother Oncol 2011:101:171-6 
HDAC inhibitor-mediated radiosensitization in human carcinoma cells: a general phenomenon? Kim IA, Kim IH, Kim HJ, Chie EK, Kim JS. J Radiat Res 2010;51(3):257-63
Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-RAS. Oh JS, Kim JJ, Byun JY, Kim IA. Int J Radiat Oncol Biol Phys 2010:76 (1):5-8
Potential prognostic value of heat-shock protein 90 in the presence of phosphatidylinositol-3-kinase overexpression or loss of PTEN, in invasive breast cancers. Song CH, Park SY, Eom KY, Kim JH, Kim SW, Kim JS, Kim IA. Breast Cancer Res 2010;12(2): R20
Targeting epidermal growth factor receptor–associated signaling pathways in non–small cell lung cancer cells: Implication in radiation response. Choi EJ, Ryu YK, Kim SY, Wu HK, Kim JS, Kim IH, Kim IA. Mol Cancer Res 2010; 8(7); 1027–36.
Targeting HER2 signaling pathway for radiosensitization: Alternative strategy for therapeutic resistance. No M, Choi EJ, Kim IA. Cancer Biology & Therapy 2009: 8(24):2351-2361
Epigenetic modulation of radiation response in human cancer cells with activated EGFR or HER-2 signaling: Potential role of histone deacetylase 6. Kim IA, No M, Lee JM et al. Radiother Oncol 2009: 92:125-132
HDAC inhibitor-mediated radiosensitization of human cancer cells: Class differences and the potential influence of p53. Kim IA, Shin JH, Kim IH et al. Clin Cancer Res 2006;2(3): 1;12:940-9
 
특허
Modulation of radiation response using microRNAs 
Composition for enhancing radiation sensitivity comprising PI4K isozyme inhibitor
Method for treating triple negative breast cancer combined with radiotherapy comprising administering phosphatidylinositol 3-kinase inhibitor and PD-1 blockade
 

연구목표
방사선치료를 근간으로 하는 면역관문억제제의 치료저항성 극복 전략에 대한 전임상연구 및 면역유전체연구를 통하여 최적의 병합치료전략 및 유용한 바이오마커를 발굴함으로서 향후 적절한 환자군을 선별하여 임상시험으로 이행할 수 있는 근거를 마련해 보고자 한다.
연구성과
논문
PI3Kγδ inhibitor plus radiation enhances the antitumor immune effect of PD-1 blockade in syngenic murine breast cancer and humanized patient-derived xenograft model. Min Guk Han, Bum-Sup Jang, Mi Hyun Kang, Deukchae Na, In Ah Kim. European Journal of Cancer 2021 in press  
PI3Kalphaδ inhibitor combined with radiation enhances the antitumor immune effect of anti-PD1 in a       syngeneic murine triple negative breast cancer model. Jang WI, Han MK, Kang MH, Park JM, Kim EE, Bae JY, Ahn S, Kim IA.  Int J Radiat Oncol Biol Phys 2021; 110(3):845-858  
Tumor mutation burden, immune checkpoint crosstalk and radiosensitivity in single-cell RNA           sequencing data of breast cancer. Jang BS, Han W, Kim IA. Radiother Oncol. 2020:142:202-209
A radiosensitivity gene signature and PD-L1 status predict clinical outcome of patients with glioblastoma multiforme in The Cancer Genome Atlas Dataset. Jang BS, Kim IA. Cancer Res Treat 2019:52(2):335-354
A radiosensitivity gene signature and PD-L1 predict the clinical outcomes of patients with lower grade glioma in TCGA. Jang BS, Kim IA. Radiother Oncol. 2018;128(2):245-253. 
Inhibition of PI4K IIIα radiosensitizes in human tumor xenograft and immune-competent syngeneic murine tumor model. Park Y, Park JM, Kim DH, Kwon J, Kim IA. Oncotarget 2017; 30;8(66):110392-110405
A radiosensitivity gene signature and PD-L1 status predict clinical outcome of patients with invasive breast carcinoma in The Cancer Genome Atlas (TCGA) dataset. Jang BS, Kim IA. Radiother Oncol 2017; 124:403-407
Targeting phosphatidylinositol 4-kinase IIIα for radiosensitization: a potential model of drug repositioning using anti-HCV agent. Kwon J, Kim DH, Park JM, Park YH, Hwang YH, Wu HG, Shin KH, Kim IA.  Int J Radiat Oncol Biol Phys 2016; 96:867-876
MicroRNA-200c increases radiosensitivity of human cancer cells with activated EGFR-associated      signaling.  Koo T, Cho. BJ, Kim DH, Park JM, Choi EJ, Kim HH, Lee DJ and Kim IA.  Oncotarget 2017;8(39): 65457-65468 
Radiosensitizing effect of lapatinib in human epidermal growth factor receptor 2-positive breast cancer cells. Yu T, Cho BJ, Choi EJ, Park JM, Kim DH, Kim IA. Oncotarget 2016;7(48): 79089-79100 
Inhibition of STAT3 enhances the radiosensitizing effect of temozolomide in glioblastoma cells in vitro and in vivo. Han TJ, Cho BJ, Choi EJ, Kim DH, Song SH, Paek SH, Kim IA. J Neurooncol. 2016;130(1):89-98
MicroRNA-203 modulates the radiation sensitivity of human malignant glioma cells. Chang JH, Hwang YH, Lee DJ, Kim DH, Park JM, Wu HG, Kim IA. Int J Radiat Oncol Biol Phys. 2016;94(2):412-20. 
Isotype-Specific Inhibition of Histone Deacetylases: Identification of Optimal Targets for Radiosensitization. Kim JH, Moon SH, No M, Kim JJ, Choi EJ, Cho BJ, Kim JS, Kim IH, Kim IA. Cancer Res Treat 2016;48(3):1130-40
The effect of chemoradiotherapy with SRC tyrosine kinase inhibitor, PP2 and Temozolomide on malignant glioma cells in vitro and in vivo. Eom KY, Cho BJ, Choi EJ, Kim JH, Chie EK, Wu HG, Kim IH, Paek SH, Kim JS, Kim IA. Cancer Res Treat 2016;48(2):687-97
Radiosensitization with combined use of olaparib and PI-103 in triple-negative breast cancer, Jang NY, Kim DH, Cho BJ, Choi EJ, Lee JS, Wu HG, Chie EK, Kim IA. BMC Cancer 2015;15:89 
Enhanced cytotoxic effect of radiation and temozolomide in malignant glioma cells: targeting PI3K-AKT-mTOR signaling, HSP90 and histone deacetylases. Choi EJ, Cho BJ, Lee DJ, Hwang YH, Chun SH, Kim HH, Kim IA. BMC Cancer. 2014 ;13;14-17
MicroRNA-7 increases radiosensitivity of human cancer cells with activated EGFR-associated signaling. Lee KM, Choi EJ, Kim IA. Radiother Oncol 2011:101:171-6 
HDAC inhibitor-mediated radiosensitization in human carcinoma cells: a general phenomenon? Kim IA, Kim IH, Kim HJ, Chie EK, Kim JS. J Radiat Res 2010;51(3):257-63
Lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-RAS. Oh JS, Kim JJ, Byun JY, Kim IA. Int J Radiat Oncol Biol Phys 2010:76 (1):5-8
Potential prognostic value of heat-shock protein 90 in the presence of phosphatidylinositol-3-kinase overexpression or loss of PTEN, in invasive breast cancers. Song CH, Park SY, Eom KY, Kim JH, Kim SW, Kim JS, Kim IA. Breast Cancer Res 2010;12(2): R20
Targeting epidermal growth factor receptor–associated signaling pathways in non–small cell lung cancer cells: Implication in radiation response. Choi EJ, Ryu YK, Kim SY, Wu HK, Kim JS, Kim IH, Kim IA. Mol Cancer Res 2010; 8(7); 1027–36.
Targeting HER2 signaling pathway for radiosensitization: Alternative strategy for therapeutic resistance. No M, Choi EJ, Kim IA. Cancer Biology & Therapy 2009: 8(24):2351-2361
Epigenetic modulation of radiation response in human cancer cells with activated EGFR or HER-2 signaling: Potential role of histone deacetylase 6. Kim IA, No M, Lee JM et al. Radiother Oncol 2009: 92:125-132
HDAC inhibitor-mediated radiosensitization of human cancer cells: Class differences and the potential influence of p53. Kim IA, Shin JH, Kim IH et al. Clin Cancer Res 2006;2(3): 1;12:940-9
 
특허
Modulation of radiation response using microRNAs 
Composition for enhancing radiation sensitivity comprising PI4K isozyme inhibitor
Method for treating triple negative breast cancer combined with radiotherapy comprising administering phosphatidylinositol 3-kinase inhibitor and PD-1 blockade
 
구성원
성명 소속 직급
김인아 서울대학교 의과대학 교수
장범섭 서울대학교 의과대학 교수
위찬우 서울대학교 의과대학 교수
한민국 서울대학교 의과대학 연구원
강미현 서울대학교 의과대학 연구원
장원익 서울대학교 의과대학 연구원
송준영 서울대학교 의과대학 연구원
김민지 서울대학교 의과대학 연구원