The Zheng Lab studies dynamic communications in cancer cells. The survival of cells depends on their ability to detect, rely and response to dynamic environmental cues in a precise and timely fashion. Signaling transduction networks provide the molecular basis for cellular signaling processing and decision-making and their misregulations is a key mechanism driving the development of neoplastic diseases.
Signaling networks often consist of a vast number of proteins and function as a highly sophisticate machine dynamically assembled or disassembled on-demand in response to external cues to control specific cellular functions. We tickle the complexity of protein networks through understanding the dynamic changes of signaling networks at the global level by deploying novel proteomics techniques such as quantitative mass spectrometry.
A main focus of our research is to dissect signaling networks controlled by receptor tyrosine kinases (RTKs), such as the ErbB family members, at the cell membrane and within specific intracellular compartments.
Our aim is to advance our understanding on how cell signals go awry in cancers and to develop innovative cancer therapies by identifying novel drug targets.
1. Soliman MA, Abdel Rahman AM, Lamming DA, Birsoy K, Frigolet M, Lu H, Fantus IG, Zheng Y, Sabatini DM, Dennis JW, Pawson T. The adaptor p66Shc inhibits mTOR-dependent anabolic metabolism. Science Signaling, 2014, 7(313): ra 17
2. Petschnigg J, Groisman B, Kotlyar M, Taipale M, Zheng Y, Kurat CF, Sayad A, Sierra JR, Mattiazzi-Usaj M, Snider J, Nachmann A, Krykbaeva I, Tsao MS, Moffat J, Pawson T, Lindquist S, Jurisica I, Stagljar I. The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells. Nature Method, 2014 (5):585-92.
3. Pasculescu A, Creixell P*, Schoof EM*, Zheng Y, Olhovsky M, Tian R, So J, Vanderlaan RD, Pawson T, Linding R, Colwill K. CoreFlow: A flexible playground for integration, analysis and modeling of complex biological data. Journal of Proteomics, 2014, pii: S1874-3919(14) 00041-4. *Equal contribution
4. Zheng Y, Zhang C, Croucher DR, Soliman MA, St-Denis N, Pasculescu A, Taylor L, Tate SA, Hardy WR, Cowill K, Dai AY, Bagshaw R, Dennis JW, Gingras AC, Daly RJ, Pawson T. Regulation of protein signaling networks by the scaffold protein Shc1 in time and space. Nature, 2013, 499(7457):166-71. Article.
· Nominated in “2013: Signaling Breakthroughs of the Year” by Science Signaling. Berndt JD and Gough NR, 2014, 7:eg1
5. Ursini-Siegel J, Hardy WR, Zheng Y, Ling C, Zuo D, Zhang C, Podmore L, Pawson T, Muller WJ. The ShcA SH2 domain engages a 14-3-3/PI3'K signaling complex and promotes breast cancer cell survival. Oncogene, 2012, 31(48): 5038-44.
6. Dyson MR, Zheng Y, Zhang C, Colwill K, Pershad K, Kay BK, Pawson T, McCafferty J. Mapping protein interactions by combining antibody affinity maturation and mass spectrometry. Analytical Biochemistry, 2011, 417(1): 25-35.
7. Zhang P*, Zheng Y*, Shi J, Zhang Y, Liu S, Liu Y, Zheng D. Targeting a novel N-terminal epitope of death receptor 5 triggers tumor cell death. Journal of Biological Chemistry, 2010, 285(12):8953-66. *equal contribution.
8. Zheng Y, Liu HZ, Coughlin J, Zheng J, Li L, Stone JC. Phosphorylation of RasGRP3 on threonine 133 provides a mechanistic link between PKC and Ras signaling systems in B cells. Blood, 2005, 105(9):3648-54.