陈良博士
- 基本信息
- 教育经历
- 工作经历
- 研究概述
- 发表文章

陈良 博士
北京生命科学研究所研究员
Liang Chen, Ph.D. Assistant Investigator, NIBS, Beijing,China
Phone:010-80726688-8380
Fax: 010-80727511
E-mail:chenliang@nibs.ac.cn
教育经历
Education
2002年 |
中国科学院上海生物化学和细胞生物学研究所,细胞生物学博士学位 |
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Ph.D. in Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese |
1996年 |
杭州大学生物系学士学位 |
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B.S. in Biotechnology, Department of Biology, |
工作经历
Professional Experience
2010年- |
北京生命科学研究所研究员 |
|
Assistant Investigator, National Institute of Biological Sciences, |
2005-2010年 |
哈佛大学医学院Dana-Farber癌症研究所博士后 |
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Postdoctoral Fellow,Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School |
2002- 2005年 |
耶鲁大学医学院博士后 |
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Postdoctoral Fellow,Department of Internal Medicine, Yale University School of Medicine |
研究概述
肺癌和肝癌是对中国癌症病人威胁最大的两种肿瘤。中国大陆每年分别有六十万和二十三万人死于肺癌和肝癌。本实验室最终目标是控制这两种癌症。我们的研究将具体在以下四个方面进行:
1. |
寻找驱动中国人肺癌和肝癌癌变的关键癌基因。较之于正常细胞,虽然一个癌细胞在遗传水平和表观遗传水平有很多改变,但当关键的癌基因被灭活后,癌细胞的生长和增殖将受到严重的影响。本实验室的一个重要方向是寻找驱动中国人肺癌和肝癌病变的关键癌基因,为靶向治疗奠定基础。 |
2. |
探究癌变早期时抑癌基因的变化。正常组织细胞有一套完善的抑瘤机制来防止细胞的癌变。在癌变早期,与癌基因功能获得性突变平行的是抑癌基因的功能紊乱。我们将在细胞水平和动物模型水平上来研究癌变早期抑癌基因的变化。 |
3. |
开发肺癌和肝癌的靶向治疗手段。至今,尽管有比较多的癌症治疗手段可供选择,但肺癌和肝癌病人的五年存活率仍然很低。我们将在细胞和动物水平上来探究有特定癌基因驱动的肺癌和肝癌的肿瘤生物学。基于此,我们将设计针对该种肿瘤的靶向疗法,并用小鼠模型来初步确证该治疗手段的有效性。 |
4. |
寻找肿瘤早期诊断的标志蛋白。控制肺癌和肝癌最有效的手段是早期诊断,因为此时可以有效地治疗或手术切除。我们将用已鉴定的小鼠模型来寻找血清中的标志蛋白,以便于早期诊断,再在病人血样中确证。 |
Research Description
Lung cancer and liver cancer are the two biggest threats to Chinese cancer patients, which claim yearly 600,000 lives and 230,000 lives respectively in mainland China. The ultimate goal of research in our laboratory is to cure both diseases. Specifically, research will focus on the following four areas:
1. |
Identifying key oncogenes responsible for tumorigenesis of lung cancer and liver cancer in Chinese cancer patients. It’s been shown that although a cancer cell has many genetic and epigenetic alterations, survival and proliferation of the cancer cell is often severely affected by inactivation of a single key oncogene. One important area of our lab is to identify oncogenes responsible for driving tumorigenesis in Chinese lung cancer and liver cancer patients, which is the first step for developing targeting therapies. |
2. |
Deciphering the changes happened to tumor suppressor genes in the process of tumorigenesis. In parallel to gain-of-function mutation in oncogenes, deregulation in tumor suppressor genes plays an important role in tumorigenesis. We will use cellular and mouse models to study the genetic and epigenetic changes happened in tumor suppressor genes during tumorigenesis. |
3. |
Developing targeting therapies against lung cancer and liver cancer. Despite the multimodality therapies against both cancers, the 5 year survival rate remains disappointingly low for both lung cancer and liver cancer. Effective therapies are desperately needed in clinic. Both cellular and mouse models will be utilized to characterize the biology of the tumor driven by a given oncogene. Based on that information, we will design and run a preclinical trial in mouse model with small chemicals/antibodies developed. |
4. |
Identifying serum protein biomarkers for early diagnosis of lung and liver cancer. The most effective way to benefit cancer patients is through diagnose cancers at early stage when the tumor can be successfully treated or surgically removed. With well-characterized mouse model that develop tumors after activation of oncogenic transgene, we will collect serum from mouse with early stage tumors. By comparing the serum samples from tumor-bearing mouse and well-controlled healthy siblings through mass-spectrometry, we plan to look for the protein biomarkers that are selectively present in the tumor-bearing mouse. The potential use of these biomarkers will then be confirmed on the patients’ sera. |
发表文章
Publications
30. Zhang H, Zhan C, Ke J, Xue Z, Zhang A, Xu K, Shen Z, Yu L, Chen L.,
EGFR Kinase domain mutation positive lung cancers are sensitive to intrapleural perfusion with hyperthermic chemotherapy (IPHC) complete treatment, Oncotarget, 2015 Dec 8. DOI: 10.18632/oncotarget.6491
29. Xu N., Fang W., Mu L., Tang Y., Gao L., Ren S., Cao D., Zhou L., Zhang A., Liu D., Zhou C., Wong K., Yu L., Zhang L., Chen L., Overexpression of wildtype EGFR is tumorigenic and denotes a therapeutic target in non-small cell lung cancer. Oncotarget, 2015 Dec 4. doi: 10.18632/oncotarget.6461
28. Gao L., Jiang Y., Mu L., Liu Y., Wang F, Wang P., Zhang A., Tang N., Chen T., Luo M., Yu L., Gao S., Chen L. Efficient Generation of Mice with Consistent Transgene Expression by FEEST, Sci Rep. 2015, 5:16284; doi: 10.1038/srep16284
27. Liu ZH, Hu JL, Liang JZ, Zhou AJ, Li MZ, Yan SM, Zhang X, Gao S, Chen L, Zhong Q, Zeng MS., Far upstream element-binding protein 1 is a prognostic biomarker and promotes nasopharyngeal carcinoma progression. Cell Death Dis. 2015 Oct 15;6:e1920
26. Hu Z, Hu Y, Liu X, Xi R, Zhang A, Liu D, Xie Q and Chen L, Tumor driven by gain-of-function HER2 H878Y mutant is highly sensitive to HER2 inhibitor, Oncotaget, 2015 Oct 13;6(31):31628-39. doi: 10.18632/oncotarget.5221
25. Wu H, Wang A, Zhang W, Wang B, Chen C, Wang W, Hu C, Ye Z, Zhao Z, Wang L, Li X, Yu K, Liu J, Wu J, Yan X, Zhao P, Wang J, Wang C, Weisberg E, Gray N, Yun C, Liu J, Chen L#, Liu Q#. Ibrutinib selectively and irreversibly targets EGFR (L858R, Del19) mutant but is moderately resistant to EGFR (T790M) mutant NSCLC Cells. Oncotarget, 2015 Oct 13;6(31):31313-22. doi: 10.18632/oncotarget.5182 (# co-coresponding)
24. Zhang H, Cao J, Li L, Liu Y, Zhao H, Li N, Li B, Zhang A, Huang H, Chen S, Dong M, Yu L, Zhang J, Chen L., Identification of urine protein biomarkers with the potential for early detection of lung cancer. Sci Rep. 2015 Jul 2;5:11805. doi: 10.1038/srep11805.
23. Hu Z, Wan X, Hao R, Zhang H, Li L, Li L, Xie Q, Wang P, Gao Y, Chen S, Wei M, Luan Z, Zhang A, Huang N, Chen L., Phosphorylation of Mutationally Introduced Tyrosine in the Activation Loop of HER2 Confers Gain-of-Function Activity. PLoS One. 2015 Apr 8;10(4):e0123623.
22. Zhu G, Fan Z, Ding M, Zhang H, Mu L, Ding Y, Zhang Y, Jia B, Chen L, Chang Z, Wu W, An EGFR/PI3K/AKT axis promotes accumulation of the Rac1-GEF Tiam1 that is critical in EGFR-driven tumorigenesis. Oncogene. 2015 Mar 9. doi: 10.1038/onc.2015.45
21. Ding X, Yang Y, Han B, Du C, Xu N, Huang H, Cai T, Zhang A, Han ZG, Zhou W, Chen L. Transcriptomic characterization of hepatocellular carcinoma with CTNNB1 mutation. PLoS One. 2014 May 5;9(5):e95307
20. Chen Z, Akbay EA, Mikse OR, Tupper T, Cheng K, Wang Y, Tan X, Altabef A, Woo SA, Chen L, Reibel J, Janne PA, Engelman JA, Sharpless NE, Kung AL, Shapiro GI, Wong KK. Co-clinical trials demonstrate superiority of crizotinib to chemotherapy in ALK-rearranged non-small cell lung cancer and predict strategies to overcome resistance. Clin Cancer Res. 2014 Mar 1;20(5):1204-11.
19. Cho J, Chen L, Sangji N, Okabe T, Yonesaka K, Francis JM, Flavin RJ, Johnson W, Kwon J, Yu S, Greulich HE, Johnson BE, Eck MJ, Janne PA, Wong KK, Meyerson M. Cetuximab response of lung cancer-derived EGF receptor mutants is associated with asymmetric dimerization. Cancer Res. 2013 Nov 15;73(22):6770-9
18. Shimamura T, Perera SA, Foley KP, Sang J, Rodig SJ, Inoue T, Chen L, Li D, Carretero J, Li YC, Sinha P, Carey CD, Borgman CL, Jimenez JP, Meyerson M, Ying W, Barsoum J, Wong KK, Shapiro GI Ganetespib (STA-9090), a Nongeldanamycin HSP90 Inhibitor, Has Potent Antitumor Activity in In Vitro and In Vivo Models of Non-Small Cell Lung Cancer. Clin Cancer Res. 2012 Sep 15;18(18):4973-85. Epub 2012 Jul 17.
17. Straume O, Shimamura T, Lampa MJ, Carretero J, Oyan AM, Jia D, Borgman CL, Soucheray M, Downing SR, Short SM, Kang SY, Wang S, Chen L, Collett K, Bachmann I, Wong K-K, Shapiro GI, Kalland KH, Folkman J, Watnick RS, Akslen LA, Naumov GN. Suppression of heat shock protein 27 induces long-term dormancy in human breast cancer. Proc Natl Acad Sci U S A. 2012 May 29;109(22):8699-704. Epub 2012 May 15
16. Leng L, Chen L, Fan J, Greven D, Arjona A, Du X, Austin D, Kashgarian M, Yin Z, Huang XR, Lan HY, Lolis E, Nikolic-Paterson D, Bucala R. A small-molecule macrophage migration inhibitory factor antagonist protects against glomerulonephritis in lupus-prone NZB/NZW F1 and MRL/lpr mice. J Immunol 2011 Jan 186 (1), 527-538.
15. M-C Liang, J Ma, L Chen, P Kozlowski, W Qin, D Li, J Goto, T Shimamura1, DN Hayes, M Meyerson, DJ Kwiatkowski and K-K Wong, TSC1 loss synergizes with KRAS activation in lung cancer development in the mouse and confers rapamycin sensitivity, Oncogene, 2010 Mar 18;29(11):1588-97
14. Zhou W(*), Ercan D(*), Chen L(*), Yun C(*), Li D, Capelletti M, Chirieac L, Iacob RE, Padera R, Engen JR, Wong KK, Eck M, Gray NS and Jänne PA., Novel mutant-selective EGFR kinase inhibitors against EGFR T790M, Nature, 2009 Dec 24;462(7276):1070-4, (*equal contribution)
13. Perera SA, Li D, Shimamura T, Raso MG, Ji H, Chen L, Borgman CL, Zaghlul S, Brandstetter KA, Kubo S, Takahashi M, Chirieac LR, Padera RF, Bronson RT, Shapiro GI, Greulich H, Meyerson M, Guertler U, Chesa PG, Solca F, Wistuba II, Wong KK., HER2YVMA drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy, Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):474-9.
12. Engelman JA(*), Chen L (*), Tan X, Crosby K, Guimaraes AR, Upadhyay R, Maira M, McNamara K, Perera SA, Song Y, Chirieac LR, Kaur R, Lightbown A, Simendinger J, Li T, Padera RF, García-Echeverría C, Weissleder R, Mahmood U, Cantley LC, Wong KK., Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med. 2008 Dec;14(12):1351-6. (* equal contribution)
11. Girnun GD (*), Chen L (*), Silvaggi J, Drapkin R, Chirieac LR, Padera RF, Upadhyay R, Vafai SB, Weissleder R, Mahmood U, Naseri E, Buckley S, Li D, Force J, McNamara K, Demetri G, Spiegelman BM, Wong KK., Regression of drug-resistant lung cancer by the combination of rosiglitazone and carboplatin. Clin Cancer Res. 2008 Oct 15;14(20):6478-86. (* equal contribution)
10. Perera SA, Maser RS, Xia H, McNamara K, Protopopov A, Chen L, Hezel AF, Kim CF, Bronson RT, Castrillon DH, Chin L, Bardeesy N, Depinho RA, Wong KK., Telomere dysfunction promotes genome instability and metastatic potential in a K-ras p53 mouse model of lung cancer. Carcinogenesis. 2008 Apr;29(4):747-53.
9. Ji H, Ramsey MR, Hayes DN, Fan C, McNamara K, Kozlowski P, Torrice C, Wu MC, Shimamura T, Perera SA, Liang MC, Cai D, Naumov GN, Bao L, Contreras CM, Li D, Chen L, Krishnamurthy J, Koivunen J, Chirieac LR, Padera RF, Bronson RT, Lindeman NI, Christiani DC, Lin X, Shapiro GI, Jänne PA, Johnson BE, Meyerson M, Kwiatkowski DJ, Castrillon DH, Bardeesy N, Sharpless NE, Wong KK., LKB1 modulates lung cancer differentiation and metastasis. Nature. 2007 Aug 16;448(7155):807-10.
8. Li D, Shimamura T, Ji H, Chen L, Haringsma HJ, McNamara K, Liang MC, Perera SA, Zaghlul S, Borgman CL, Kubo S, Takahashi M, Sun Y, Chirieac LR, Padera RF, Lindeman NI, Jänne PA, Thomas RK, Meyerson ML, Eck MJ, Engelman JA, Shapiro GI, Wong KK. Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy. Cancer Cell. 2007 Jul;12(1):81-93.
7. Ji H, Wang Z, Perera SA, Li D, Liang MC, Zaghlul S, McNamara K, Chen L, Albert M, Sun Y, Al-Hashem R, Chirieac LR, Padera R, Bronson RT, Thomas RK, Garraway LA, Jänne PA, Johnson BE, Chin L, Wong KK., Mutations in BRAF and KRAS converge on activation of the mitogen-activated protein kinase pathway in lung cancer mouse models. Cancer Res. 2007 May 15;67(10):4933-9.
6. Chen L(*), He W(*), Kim ST, Tao J, Gao Y, Chi H, Intlekofer AM, Harvey B, Reiner SL, Yin Z, Flavell RA, Craft J.. Epigenetic and Transcriptional Programs Lead to Default IFN-gamma Production by gamma/delta T Cells. 2007 Mar; J Immunol. 178(5):2730-2736. (* equal contribution)
5. Tao J, Gao Y, Li MO, He W, Chen L, Harvev B, Davis RJ, Flavell RA, Yin Z. JNK2 negatively regulates CD8(+) T cell effector function and anti-tumor immune response. Eur J Immunol. 2007 Mar;37(3):818-829.
4. Ji H, Li D, Chen L, Shimamura T, Kobayashi S, McNamara K, Mahmood U, Mitchell A, Sun Y, Al-Hashem R, Chirieac LR, Padera R, Bronson RT, Kim W, Jänne PA, Shapiro GI, Tenen D, Johnson BE, Weissleder R, Sharpless NE, Wong KK., The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. Cancer Cell. 2006 Jun;9(6):485-95.
3. Wisnewski AV, Stowe MH, Cartier A, Liu Q, Liu J, Chen L, Redlich CA., Isocyanate vapor-induced antigenicity of human albumin. J Allergy Clin Immunol. 2004 Jun;113(6):1178-1184.
2. Wisnewski AV, Herrick CA, Liu Q, Chen L, Bottomly K, Redlich CA. Human gamma/delta T-cell proliferation and IFN-gamma production induced by hexamethylene diisocyanate. J Allergy Clin Immunol. 2003 Sep;112(3):538-546.
1. Chen L, Li G, Tang L, Wang J, Ge XR, The inhibition of lung cancer cell growth by intracellular immunization with LC-1 ScFv. Cell Res. 2002 Mar;12(1):47-54.
Patent: . |
Lewis Cantley, Jeffery Engelman, Kwok-Kin Wong, and Liang Chen. BIDMC 1223: Targeted Combination Therapy and Companion Diagnostic for Treatment of Cancers Driven by RAS. US patent #61/199,021 (pending). |
Membership: |
Active Member, American Association for Cancer Research, 1/1/2007-12/31/2007. |
Meetings and conferences: |
Liang Chen, Dalia Ercan, Jeonghee Cho, Pasi A. Janne, Matthew L. Meyerson, Kwok-Kin Wong. The impact of human wild type EGFR on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies. The James Watson Symposium on Cancer, COLD SPRING HARBOR ASIA CONFERENCES (oral presentation in the conference) |
Awards/honors: |
Best abstracts (one of four). Jeonghee Cho(*), Liang Chen(*), Naveen Sangji, Jinyan Du, Takafumi Okabe, Kimio Yonesaka, Joshua M. Francis, Richard J. Flavin, Soyoung Yu, Heidi E. Greulich, Bruce E. Johnson, Michael J. Eck, Pasi A. Jänne, Kwok-Kin Wong and Matthew Meyerson. Cetuximab Resistance associated with Dimerization-Independence of Oncogenic EGFR Mutants. 5th Annual Dana-Farber/Harvard Cancer Center (DF/HCC) Lung Cancer Program Symposium , May 2009 (* equal contribution) |