系統生物學可以定義為對生物系統進行系統化的研究，藉由研究生物系統不同部分之間的相互關係與作用，期望能夠建立一個系統模型，藉此來預測完整生物體的表現。
　　Wnt和EGFR-ERK訊號傳遞途徑是已知跟細胞的增殖、分化和凋亡。本研究中，我們利用透過數學生化軟體，了解這兩個訊號傳遞途徑的動力學行為。
　　本次研究是利用2007年所提供的模型為基礎，增加幾個新反應步驟，並檢視這些新反應步驟對Wnt-EGFR訊息傳遞途徑的影響，同時也重新探討先前檢視的效應。在擴大訊息傳遞途徑，分成三部分:一.RKIP正回饋機制的修改，二.SOS負回饋機制與EGFR降解機制的添加及探討，三.AKT途徑的添加，。完成添加上述的反應機制添加，進行了研究後的到五點結果:
1. EGFR降解機制移除，造成β-catenin/TCF濃度值的上升1.75倍
2. 觀察因Wnt訊息造成的震盪現象，發現需ERK*負回饋機制與SOS負回饋機制同時存在於EGFR-ERK訊息傳遞途徑，才會造成震盪現象。
3. 把模型初始濃度調整至穩定狀態時的初始濃度，與另一組初始濃度(部分成員濃度為零)對ERK濃度影響。當移除EGFR降解反應步驟後，前者有震盪現象，後者沒有。
4. 經過修改的模型，可以描述RKIP濃度改變對ERK*濃度造成的影響。
5. 模擬當β-catenin濃度增加20倍，增加RKIP濃度可抑制ERK*濃度的增加。

[1]E. Sancho, E. Batlle, H. Clevers, Live and let die in the intestinal epithelium (vol 15, pg 763, 2003). Curr. Opin. Cell Biol. 16 (2004) 113-113.
[2]T. Reya, H. Clevers, Wnt signalling in stem cells and cancer. Nature 434 (2005) 843-850.
[3]W. Kolch, Coordinating ERK/MAPK signalling through scaffolds and inhibitors. Nat. Rev. Mol. Cell Biol. 6 (2005) 827-837.
[4]J.Y. Fang, B.C. Richardson, The MAPK signalling pathways and colorectal cancer. Lancet Oncol. 6 (2005) 322-327.
[5]J. Downward, Targeting ras signalling pathways in cancer therapy. Nat. Rev. Cancer 3 (2003) 11-22.
[6]E.H. Jho, T. Zhang, C. Domon, C.K. Joo, J.N. Freund, F. Costantini, Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol. Cell. Biol. 22 (2002) 1172-1183.
[7]J.Y. Leung, F.T. Kolligs, R. Wu, Y.L. Zhai, R. Kuick, S. Hanash, K.R. Cho, E.R. Fearon, Activation of AXIN2 expression by beta-catenin-T cell factor - A feedback repressor pathway regulating Wnt signaling. J. Biol. Chem. 277 (2002) 21657-21665.
[8]V.L. Katanaev, R. Ponzielli, M. Semeriva, A. Tomlinson, Trimeric G protein-dependent frizzled signaling in Drosophila. Cell 120 (2005) 111-122.
[9]R. Nusse, Cell biology - Relays at the membrane. Nature 438 (2005) 747-749.
[10]J.G. Paez, P.A. Janne, J.C. Lee, S. Tracy, H. Greulich, S. Gabriel, P. Herman, F.J. Kaye, N. Lindeman, T.J. Boggon, K. Naoki, H. Sasaki, Y. Fujii, M.J. Eck, W.R. Sellers, B.E. Johnson, M. Meyerson, EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science 304 (2004) 1497-1500.
[11]C.Y. Ung, H. Li, X.H. Ma, J. Jia, B.W. Li, B.C. Low, Y.Z. Chen, Simulation of the regulation of EGFR endocytosis and EGFR-ERK signaling by endophilin-mediated RhoA-EGFR crosstalk. FEBS Lett. 582 (2008) 2283-2290.
[12]R.J. Orton, O.E. Sturm, V. Vyshemirsky, M. Calder, D.R. Gilbert, W. Kolch, Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway. Biochem. J. 392 (2005) 249-261.
[13]V. De Falco, M.D. Castellone, G. De Vita, A.M. Cirafici, J.M. Hershman, C. Guerrero, A. Fusco, R.M. Melillo, M. Santoro, RET/papillary thyroid carcinoma oncogenic signaling through the Rap1 small GTPase. Cancer Res. 67 (2007) 381-390.
[14]M. Almeida, L. Han, T. Bellido, S.C. Manolagas, S. Kousteni, Wnt proteins prevent apoptosis of both uncommitted osteoblast progenitors and differentiated osteoblasts by beta-catenin-dependent and -independent signaling cascades involving Src/ERK and phosphatidylinositol 3-kinase/AKT. J. Biol. Chem. 280 (2005) 41342-41351.
[15]E. Rottinger, L. Besnardeau, T. Lepage, A Raf/MEK/ERK signaling pathway is required for development of the sea urchin embryo micromere lineage through phosphorylation of the transcription factor Ets. Development 131 (2004) 1075-1087.
[16]M.S. Yun, S.E. Kim, S.H. Jeon, J.S. Lee, K.Y. Choi, Both ERK and Wnt/beta-catenin pathways are involved in Wnt3a-induced proliferation. J. Cell Sci. 118 (2005) 313-322.
[17]D. Kim, O. Rath, W. Kolch, K.H. Cho, A hidden oncogenic positive feedback loop caused by crosstalk between Wnt and ERK Pathways. Oncogene 26 (2007) 4571-4579.
[18]R.J. Orton, M.E. Adriaens, A. Gormand, O.E. Sturm, W. Kolch, D.R. Gilbert, Computational modelling of cancerous mutations in the EGFR/ERK signalling pathway. BMC Syst. Biol. 3 (2009) 17.
[19]S.Y. Shin, O. Rath, A. Zebisch, S.M. Choo, W. Kolch, K.H. Cho, Functional Roles of Multiple Feedback Loops in Extracellular Signal-Regulated Kinase and Wnt Signaling Pathways That Regulate Epithelial-Mesenchymal Transition. Cancer Res. 70 6715-6724.
[20]S.Y. Shin, O. Rath, S.M. Choo, F. Fee, B. McFerran, W. Kolch, K.H. Cho, Positive- and negative-feedback regulations coordinate the dynamic behavior of the Ras-Raf-MEK-ERK signal transduction pathway. J. Cell Sci. 122 (2009) 425-435.
[21]K. Yeung, P. Janosch, B. McFerran, D.W. Rose, H. Mischak, J.M. Sedivy, W. Kolch, Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the Raf kinase inhibitor protein. Mol. Cell. Biol. 20 (2000) 3079-3085.
[22]K. Yeung, T. Seitz, S.F. Li, P. Janosch, B. McFerran, C. Kaiser, F. Fee, K.D. Katsanakis, D.W. Rose, H. Mischak, J.M. Sedivy, W. Kolch, Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature 401 (1999) 173-177.
[23]D. Chen, S.B. Waters, K.H. Holt, J.E. Pessin, SOS phosphorylation and disassociation of the Grb2-SOS complex by the ERK and JNK signaling pathways. J. Biol. Chem. 271 (1996) 6328-6332.
[24]E. Lee, A. Salic, R. Kruger, R. Heinrich, M.W. Kirschner, The roles of APC and axin derived from experimental and theoretical analysis of the Wnt pathway. PLoS. Biol. 1 (2003) 116-132.
[25]M.R. Rosner, MAP kinase meets mitosis: A role for Raf Kinase Inhibitory Protein in spindle checkpoint regulation. Cell Div. 2 (2007) 4.
[26]Z. Fu, Y. Kitagawa, R.L. Shen, R. Shah, R. Mehra, D. Rhodes, P.J. Keller, A. Mizokami, R. Dunn, A.M. Chinnaiyan, Z. Yao, E.T. Keller, Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer. Prostate 66 (2006) 248-256.
[27]H.Z. Li, Y. Wang, Y. Gao, J. Shao, X.L. Zhao, W.M. Deng, Y.X. Liu, J. Yang, Z. Yao, Effects of Raf kinase inhibitor protein expression on metastasis and progression of human epithelial ovarian cancer. Mol. Cancer Res. 6 (2008) 917-928.
[28]R.S. Garofalo, S.J. Orena, K. Rafidi, A.J. Torchia, J.L. Stock, A.L. Hildebrandt, T. Coskran, S.C. Black, D.J. Brees, J.R. Wicks, J.D. McNeish, K.G. Coleman, Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKB beta. J. Clin. Invest. 112 (2003) 197-208.
[29]Z.Z. Yang, O. Tschopp, A. Baudry, B. Dummler, D. Hynx, B.A. Hemmings, Physiological functions of protein kinase B/Akt. Biochem. Soc. Trans. 32 (2004) 350-354.
[30]H. Li, C.Y. Ung, X.H. Ma, X.H. Liu, B.W. Li, B.C. Low, Y.Z. Chen, Pathway Sensitivity Analysis for Detecting Pro-Proliferation Activities of Oncogenes and Tumor Suppressors of Epidermal Growth Factor Receptor-Extracellular Signal-Regulated Protein Kinase Pathway at Altered Protein Levels. Cancer 115 (2009) 4246-4263.
[31]K.S. Brown, C.C. Hill, G.A. Calero, C.R. Myers, K.H. Lee, J.P. Sethna, R.A. Cerione, The statistical mechanics of complex signaling networks: nerve growth factor signaling. Phys. Biol. 1 (2004) 184-195.
[32]J.J. Tyson, K.C. Chen, B. Novak, Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. Curr. Opin. Cell Biol. 15 (2003) 221-231.