We have a longstanding interest in studying cooperative genetic alterations that perturb cell cycle restriction and program malignant transformation. Accordingly, we have developed the experimental models in which specific genetic alterations can be investigated in isogenic contexts.
In addition, we have used genetic tools (short hairpin RNA, CRISPR and open reading frame libraries) to identify and study oncogenes, cancer pathways and related targets. By applying these tools or methods, we are in the process to study and identify genes/molecules involved in tumorigenesis, tumor maintenance, and drug sensitivity or resistance.
Over the past several years, we have been particularly interested in using these approaches to identify synthetic lethal partners to oncogenes and tumor suppressors. In particular, we are focusing on oncogenic ras and its effector pathways. We identified several candidates that appear critical for cancer cells harboring oncogenic ras to survive. Currently, we are expanding and extending our initial studies into more complex experimental models that recapitulate further aspects of human cancers.
We are using primary and tumor cell lines, 3D/organoids as well as xenograft and genetically modified mouse models for cancer biology studies. A range of cellular and molecular biological techniques are being employed.
Yan Chen, MD, PhD
Xia Wu, PhD
- Ganapathy G, Liu J, Xiong R, Yu T, Makriyannis A, Chen YC 2019 Chronic low dose arsenic exposure preferentically perturbs mitotic phase of the cell cycle. Genes & Cancer in press.
- Yu T, Ganapathy S, Shen L, Peng B, Kim SH, Makriyannis A, Chen YC 2018 Phellinus linteus extract is in synergy with camptothecin11 for inducing S phase crisis in colon cancer cells. Oncotarget 9: 6308.
- Ganapathy S, Li P, Lafontant J, Xiong R, Yu T, Zhang G, Chen YC 2017 Chromium IV expresure, via Src/Ras signaling, promotes tumorigenesis in human lung and skin cells. Toxicol Appl Pharm. 56: 1808.
- Choi B, Chen X, Chen YC, Dai W. 2016 WWP2 is required for normal cell cycle progression. Genes & Cancer 6: 371.
- Chen H, Guan R, Lei Y, Chen J, Ge Q, Dou R, Zhang X, Chen H, Qi X, Zhou X, Chen YC. 2015 Lymphangiogenesis in gastric cancer regulated through Akt/mTOR-VEGF-C/VEGF-D axis. BMC Cancer 15: 103.
- Zhou X, Kim SH, Shen L, Lee HJ, Chen YC. 2014 Activation of mitotic catastrophe in NF1 deficient cells by PKC inhibition. Cell Cycle 13: 2340.
- Nishioka T, Luo LY, Shen L, He H, Chen YC. 2014 Nicotine exposure increases the resistance of cancer cells to cisplatin through enhancing Bcl-2 stability. Bri J of Cancer 110: 1785.
- Shen L, Nishioka T, Guo J, Chen YC. 2012 Geminin functions downstream of p53 in v-K-ras-induced DHFR amplification. Cancer Res. 72: 6153.