Liang Chen, Ph.D. - Scientists&Research - 北京生命科学研究所

Liang Chen, Ph.D.

Assistant Investigator, NIBS, Beijing，China

Phone：010-80726688-8380

Fax： 010-80727511

E-mail：chenliang@nibs.ac.cn

Education

2002	Ph.D. in Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, China

1996	B.S. in Biotechnology, Department of Biology, Hangzhou University, Zhejiang, China

Professional Experience


2010-	Assistant Investigator, National Institute of Biological Sciences, Beijing, China
2005-2010	Postdoctoral Fellow，Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School
2002- 2005	Postdoctoral Fellow，Department of Internal Medicine, Yale University School of Medicine

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.

Publications

1. 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

2. 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.

3. 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

4. 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.

5.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

6. 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 Immunol2011 Jan 186 (1), 527-538.

7. 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

8. 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)

9. 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.

10. 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)

12. 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.

13. 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.

14. 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.

15. 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.

16. 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)

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.