The central question the Wang lab is interested in investigating is what are the signaling networks underlying tissue homeostasis and organ size control as well as the role of their dysregulation in tumorigenesis. The recognition in the past decade that the Hippo pathway is a crucial signaling pathway in organ size control, allowed us to take the first step to achieve this long-term goal.
We are majorly working on the two areas in the lab:
1. Dissecting and targeting the Hippo pathway for cancer treatment.
Our previous proteomic analysis established the protein-protein interaction network for the human Hippo pathway, which helped to uncover a number of potential novel Hippo regulators. We are characterizing the cellular functions of these regulators, and examining their roles in organ size control and tumorigenesis. Since Hippo pathway is a crucial tumor suppressor pathway, we also hope to explore the therapeutic potentials by utilizing the Hippo pathway for cancer therapy.
2. Defining the protein-protein interaction landscape involved in organ size control and tissue homeostasis.
Coordination of key signaling pathways required for cell proliferation and survival may contribute to the elegant mechanisms underlying organ size control and tissue homeostasis. To achieve a comprehensive understanding of this process, we have defined the protein-protein interaction networks for several key signaling pathways/protein families related to growth control and cancer development, especially how they crosstalk with the Hippo pathway by utilizing the proteomic approach. We expect that these studies will also generate additional clues to help us unravel the molecular basis of the Hippo pathway in organ size control and cancer prevention.
Selected Publications (Complete list of published work: https://www.ncbi.nlm.nih.gov/myncbi/1fcEFO6Btur5-/bibliography/public)
- Seo G, Wang W. Putting a leash on Hippo. Nature Chemical Biology. 2022 Jul 4. doi: 10.1038/s41589-022-01066-8. Online ahead of print.PMID: 35788179
- Han H, Mahieu A, de Paula LD, Wang W. Functional interplay between the Hippo pathway and heavy metals. Mol Cell Oncol. 2022 Apr 9;9(1):2061297. doi: 10.1080/23723556.2022.2061297. eCollection 2022.PMID: 35434269
- Kattan RE, Han H, Seo G, Yang B, Lin Y, Dotson M, Pham S, Menely Y, Wang W. Interactome analysis of human phospholipase D and phosphatidic acid-associated protein network. Mol Cell Proteomics. 2022 Jan 7:100195. doi: 10.1016/j.mcpro.2022.100195. PMID: 35007762
- Han H, Nakaoka HJ, Hofmann L, Zhou JJ, Yu C, Zeng L, Nan J, Seo G, Vargas RE, Yang B, Qi R, Bardwell L, Fishman DA, Cho KWY, Huang L, Luo R, Warrior R#, Wang W#. The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1. Nature Cell Biology. 2022 Jan 13. doi: 10.1038/s41556-021-00813-8. PMID: 35027733. (# co-corresponding authors)
- Bian W, Tang M, Jiang H, Xu W, Hao W, Sui Y, Hou Y, Nie L, Zhang H, Wang C, Li N, Wang J, Qin J, Wu L, Ma X#, Chen J#, Wang W#, Li X#. Low-density-lipoprotein-receptor-related protein 1 mediates Notch pathway activation. Developmental Cell. 2021 Oct 25;56(20):2902-2919.e8. doi: 10.1016/j.devcel.2021.09.015. Epub 2021 Oct 8.PMID: 34626540 (# co-corresponding authors)
- Zhou Z, Yuan Z, Hong W, Wang W. Editorial: A Hippo’s View: From Molecular Basis to Translational Medicine. Front Cell Dev Biol. 2021 Jul 23;9:729155. doi: 10.3389/fcell.2021.729155. eCollection 2021.PMID: 34368170
- Seo G, Han H, Vargas RE, Yang B, Li X, Wang W. MAP4K Interactome Reveals STRN4 as a Key STRIPAK Complex Component in Hippo Pathway Regulation. Cell Reports. 2020 Jul 7;32(1):107860. doi: 10.1016/j.celrep.2020.107860.PMID: 32640226
- Vargas RE, Wang W. Significance of long non-coding RNA AGPG for the metabolism of esophageal cancer. Cancer Commun (Lond). 2020 May 25. doi: 10.1002/cac2.12035. PMID: 32449319
- Chen Y, Han H, Seo G, Vargas RE, Yang B, Chuc K, Zhao H, Wang W. Systematic analysis of the Hippo pathway organization and oncogenic alteration in evolution. Scientific Reports. 2020 Feb 21. PMID: 32081887; DOI: 10.1038/s41598-020-60120-4
- Vargas RE, Duong VT, Han H, Ta AP, Chen Y, Zhao S, Yang B, Seo G, Chuc K, Oh S, El Ali A, Razorenova OV, Chen J#, Luo R#, Li X#, Wang W#. Elucidation of WW domain ligand binding specificities in the Hippo pathway reveals STXBP4 as YAP inhibitor. EMBO Journal. 2019 Nov 29:e102406. doi: 10.15252/embj.2019102406. PMID:31782549. (# co-corresponding authors)
- Han H, Vargas R, Seo G, Wang W. Phosphatidic acid: a lipid regulator of the Hippo pathway. Molecular & Cellular Oncology. 2018 Dec 30. https://doi.org/10.1080/23723556.2018.1558683
- Han H, Qi R, Zhou JJ, Ta AP, Yang B, Nakaoka HJ, Seo G, Guan KL, Luo R, Wang W. Regulation of the Hippo Pathway by Phosphatidic Acid-Mediated Lipid-Protein Interaction. Molecular Cell. 2018 Sep 13. pii: S1097-2765(18)30698-1. doi: 10.1016/j.molcel.2018.08.038. PMID: 30293781
- Han H, Yang B, Nakaoka HJ, Yang J, Zhao Y, Le Nguyen K, Bishara AT, Mandalia TK, Wang W. Hippo signaling dysfunction induces cancer cell addiction to YAP. Oncogene. 2018 Aug 1. doi: 10.1038/s41388-018-0419-5.
- Zheng X, Han H, Liu GP, Ma YX, Pan RL, Sang LJ, Li RH, Yang LJ, Marks JR, Wang W#, Lin A#. LncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism. EMBO Journal. 2017; 36(22):3325-3335. (# co-corresponding authors)
- Han H, Yang B, Wang W. Angiomotin-like 2 interacts with and negatively regulates AKT. Oncogene. 2017; 36(32):4662-4669.
- Li X, Han H, Zhou MT, Yang B, Ta AP, Li N, Chen J#, Wang W#. Proteomic Analysis of the Human Tankyrase Protein Interaction Network Reveals Its Role in Pexophagy. Cell Reports. 2017; 20(3):737-749. (# co-corresponding authors)
- Li X, Tran KM, Aziz KE, Sorokin AV, Chen J#, Wang W#. Defining the Protein-Protein Interaction Network of the Human Protein Tyrosine Phosphatase Family. Mol Cell Proteomics. 2016; 15(9):3030-44. (# co-corresponding authors)
- Li X*, Wang W*, Xi Y, Gao M, Tran M, Aziz KE, Qin J, Li W, Chen J. FOXR2 Interacts with MYC to Promote Its Transcriptional Activities and Tumorigenesis. Cell Reports. 2016; 16(2):487-497. (* co-first authors)
- Wang W, Li N, Li X, Tran MK, Han X, Chen J. Tankyrase Inhibitors Target YAP by Stabilizing Angiomotin Family Proteins. Cell Reports. 2015; 13(3):524-532.
- Wang W, Li X, Chen J. Energy crisis and the Hippo pathway. Cell Cycle. 2015; 14(13):1995-6.
- Wang W, Xiao ZD, Li X, Aziz KE, Gan B, Johnson RL, Chen J. AMPK modulates Hippo pathway activity to regulate energy homeostasis. Nature Cell Biology. 2015; 17(4):490-9.
- Wang W*, Li X*, Lee M, Jun S, Aziz KE, Feng L, Tran MK, Li N, McCrea PD, Park JI, Chen J. FOXKs promote Wnt/β-catenin signaling by translocating DVL into the nucleus. Developmental Cell. 2015; 32(6):707-18. (* co-first authors)
- Li X*, Wang W*, Wang J, Malovannaya A, Xi Y, Li W, Guerra R, Hawke DH, Qin J, Chen J. Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes. Molecular Systems Biology. 2015; 11(1):775. (* co-first authors)
- Wang W*, Li X*, Huang J, Feng L, Dolinta KG, Chen J. Defining the protein-protein interaction network of the human hippo pathway. Mol Cell Proteomics. 2014; 13(1):119-31. (* co-first authors)
- Wang W, Huang J, Wang X, Yuan J, Li X, Feng L, Park JI, Chen J. PTPN14 is required for the density-dependent control of YAP1. Genes & Development. 2012; 26(17):1959-71.
- Wang W, Huang J, Chen J. Angiomotin-like proteins associate with and negatively regulate YAP1. Journal of Biological Chemistry. 2011; 286(6):4364-70.