WEIMIN LI, MD, PhD
- College of Pharmacy and Pharmaceutical Sciences
Education and Training
- M.Sc. in Medical Molecular Genetics, University of Aberdeen, UK
- M.D. specialized in Oncology, Shandong, China
- Ph.D. in Biochemistry, University of Basel, Switzerland
- Postdoctoral Training: National Cancer Institute/NIH & University of Wisconsin-Madison
My primary research focus is studying the mechanisms of cancer cell survival and growth using tissue-mimicking culture systems and animal models. Cancer cells gain proliferation potential by acquiring either gene mutations resulting in altered protein products or disequilibration of expression of growth promoting and repressing factors. These chaotic molecular changes of the cells favor cancer cell survival, growth, and metastasis.
Tumor tissue environment: Native cancer cells within a tumor live in extracellular matrix (ECM) that also contains stromal cells and blood vessels. This heterogeneous ECM space is structurally modified with the growth of the tumor and the infiltration of biomolecules secreted by the cancer cells and stromal cells in addition to those diffused from capillaries. These mechanical and biochemical features of tumor tissues are different from those of normal tissues, and are essential for the signal-sensitive cellular functions and behaviors. Cells grown in a three-dimensional (3D) tissue microenvironment express distinct biomolecules and phenotypes that would otherwise difficult to be captured in 2D cultures. We use innovative tissue matrix scaffold (TMS) 3D cultures (native ECM scaffolds) coupled with animal models to study tumor biology and the molecular mechanisms controlling cancer progression.
Nuclear signaling regulation of tumor growth: The cell nucleus carries genetic information and harbors unique regulatory molecules required for cell survival and growth. The phosphoinositide-3 kinase (PI3K)/protein kinase B (PKB, also known as Akt) signaling pathway plays a critical role in tumorigenesis (formation of tumor) and cancer progression. This pathway is hyperactive in most cancers. While the cytoplasmic functions of the PI3K/Akt cascades have been well studied, our understanding of PI3K/Akt signaling and its regulation within the cell nucleus is limited. Our group is interested in the nuclear factors that control or are regulated by PI3K and Akt activities required for oncogene or tumor suppressor gene expression and cell cycle progression. We use well-established cell and animal models, including live imaging and 3D culturing of cancer cells as well as other biochemical and molecular biological tools, to study the nuclear roles of the PI3K/Akt pathway in cancer development. Our long-term goal is to translate the research findings into pharmacological and clinical approaches to cure human cancers.
- Ruud KF, Hiscox WC, Yu I, Chen RK, and Li W. Distinct phenotypes of cancer cells on tissue matrix gel.Breast Cancer Res.2020 Jul 31; 22:82. doi:10.1186/s13058-020-01321-7
- Shinsato Y, Doyle AD, Li W, Yamada KM.Direct comparison of five different 3D extracellular matrix model systems for characterization of cancer cell migration.Cancer Reports. 2020 June 8; doi: 10.1002/cnr2.1257.
- Liu S-T, Chan GK and Li W. Editorial: Non-cell Cycle Functions of Cell Cycle Regulators. Front. Cell Dev. Biol. 2019 June 27; 7:122. doi: 10.3389/fcell.2019.00122
- Rijal G, Wang J, Yu I, Gang DR, Chen RK, Li W.Porcine Breast Extracellular Matrix Hydrogel for Spatial Tissue Culture.Int J Mol Sci. 2018 Sep 25; 19(10). pii: E2912. doi: 10.3390/ijms19102912
- Rijal G and Li W. Native-mimicking in vitro microenvironment: an elusive and seductive future for tumor modeling and tissue engineering. J Biol Eng. 2018 Sep 12; 12:20. doi: 10.1186/s13036-018-0114-7
- Rijal G, Bathula C, and Li W. Application of synthetic polymeric scaffolds in breast cancer 3D tissue cultures and animal tumor models. Int J Biomater. 2017 December; 2017:1-9. doi: 10.1155/2017/8074890
- Rijal G and Li W. A versatile 3D tissue matrix scaffold system for tumor modeling and drug screening. Sci. Adv. 2017 Sep 13;3, e1700764. doi: 10.1126/sciadv.1700764
- Li W*, Li W, Laishram RS, Hoque M, Ji Z, Tian B*, Anderson RA*. Distinct regulation of alternative polyadenylation and gene expression by nuclear poly(A) polymerases. Nucleic Acids Res. 2017 June 27; 45(12). doi: 10.1093/nar/gkx560
- Rijal G and Li W. 3D scaffolds in breast cancer research. Biomaterials. 2016 March; 81:135-156. doi: 10.1016/j.biomaterials
- Davis WJ, Lehmann PZ andLi W. Nuclear PI3K signaling in cell growth and tumorigenesis.Front. Cell Dev. Biol. 2015 Apr 13; 3:24. doi: 10.3389/fcell.2015.00024
- Li Wand Anderson RA. Star-PAP mediates HPV E6 regulation of p53 and sensitizes cells to VP-16.Oncogene. 2014 Feb 13; 33(7):928-32. doi: 10.1038/onc.2013.14
- Ray D, Kazan H, Cook KB, Weirauch MT, Najafabadi HS, Li X, Gueroussov S, Albu M, Zheng H, Yang A, Na H, Irimia M, Matzat LH, Dale RK, Smith SA, Yarosh CA, Kelly SM, Nabet B, Mecenas D,Li W, Laishram RS, Qiao M, Lipshitz HD, Piano F, Corbett AH, Carstens RP, Frey BJ, Anderson RA, Lynch KW, Penalva LO, Lei EP, Fraser AG, Blencowe BJ, Morris QD, Hughes TR. A compendium of RNA-binding motifs for decoding gene regulation.Nature. 2013 Jul 11; 499(7457):172-7. doi: 10.1038/nature12311
- Li W,Laishram RS, and Anderson RA. The novel poly(A) polymerase Star-PAP is a signaling-regulated switch at the mRNA 3’-end during stress response.Advances in Biological Regulation. 2013 Jan; 53(1):64-76. doi: 10.1016/j.jbior.2012.10.004
- Li W, Laishram RS, Ji Z, Barlow C, Tian B, and Anderson RA. Star-PAP Control of BIK Expression and Apoptosis is Regulated by Nuclear PIPKIa and PKCd Signaling.Molecular Cell. 2012 Jan 13; 45(1):25-37. doi: 10.1016/j.molcel.2011.11.017.
- Schramp M, Hedman A,Li W(equal contribution as first), Tan X and Anderson RA. PIP Kinases from the Cell Membrane to the Nucleus. Subcell Biochem, Springer, (Book Chapter: Phosphoinositide I: Enzymes of Synthesis and Degradation). 2012; 58:25-59. doi: 10.1007/978-94-007-3012-0_2
- Li W, Kotoshiba S, Berthet C, Hilton MB, Kaldis P. Rb/Cdk2/Cdk4 triple mutant mice elicit an alternative mechanism for regulation of the G1/S transition.PNAS. 2009 Jan 13; 106(2):486-91. doi: 10.1073/pnas.0804177106
- Li W, Kotoshiba S, Kaldis P. Genetic mouse models to investigate cell cycle regulation.Transgenic Res.2009 Aug; 18(4):491-8. doi: 10.1007/s11248-009-9276-x
- Li W, Petrimpol M, Molle KD, Hall MN, Battegay EJ, Humar R. Hypoxia-induced endothelial proliferation requires both mTORC1 and mTORC2.Circ Res.2007 Jan 5; 100(1):79-87