Wang, Zhu - University of California, Santa Cruz - Molecular, Cell & Developmental Biology Faculty

个人简介

B. S., Peking University Ph.D., Columbia University Postdoctorate, Columbia University Medical Center

研究领域

We are interested in understanding cell type specification, stem cell differentiation, and various cell behaviors in vivo, with a particular focus on the prostate gland. To tackle these questions, we employ multiple experimental approaches, including animal models, genetic lineage tracing, molecular and cell assays, and bioinformatic analyses. Ultimately, a better understanding in this field will facilitate prevention and treatment of diseases such as prostate cancer. Currently, the lab is focused on the following research areas: Prostate Basal Stem Cell Plasticity Prostate epithelial basal cells behave as adult stem cells to produce luminal cells during prostate organogenesis. However, in the mature prostate, basal stem cell activities are significantly restricted, and basal-to-luminal cell differentiation becomes rare. Interestingly, basal-to-luminal differentiation is greatly enhanced under oncogenic or inflammatory conditions. Are tumorigenic basal cells in a state similar to that of the young adult basal stem cells? We are dissecting the internal and extrinsic signaling pathways that regulate the stem cell plasticity of prostate basal cells. AR and Nkx3.1 in Prostate Homeostasis and Cancer The male hormone androgen regulates numerous aspects of prostate physiology and cancer progression through the transcription factor androgen receptor (AR). Despite the use of androgen-deprivation therapy (ADT) in the clinics, prostate cancer almost always relapse after this treatment. This can be partially attributed to the distinct roles of AR in different cell types of the organ. We recently found AR to be cell-autonomously required for stem cell activities of basal stem cells as well as a type of luminal stem cell called CARNs. CARNs are distinguished by the expression of the gene Nkx3.1 in luminal cells after androgen deprivation. Being a transcriptional target gene of AR, Nkx3.1 encodes a key regulator of prostate cell fate specification and tumor suppressor. We are investigating the molecular mechanisms by which AR and Nkx3.1 orchestrate different cell behaviors in prostate homeostasis and cancer initiation.

近期论文

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Novel Method of Plasmid DNA Delivery to Mouse Bladder Urothelium by Electroporation. Yu C, Stefanson O, Liu Y, Wang ZA. J Vis Exp. 2018 May 3;(135). doi: 10.3791/57649. Transcriptional regulation of the Nkx3.1 gene in prostate luminal stem cell specification and cancer initiation via its 3' genomic region. Xie Q, Wang ZA. J Biol Chem. 2017 Aug 18;292(33):13521-13530. doi: 10.1074/jbc.M117.788315. Epub 2017 Jul 5. Dissecting cell-type-specific roles of androgen receptor in prostate homeostasis and regeneration through lineage tracing. Xie Q, Liu Y, Cai T, Horton C, Stefanson J, Wang ZA. Nat Commun. 2017 Jan 23;8:14284. doi: 10.1038/ncomms14284. Comparative lineage tracing reveals cellular preferences for prostate cancer initiation. Wang ZA, Shen MM. Mol Cell Oncol. 2015 Feb 25;2(3):e985548. doi: 10.4161/23723556.2014.985548. eCollection 2015 Jul-Sep. Luminal cells are favored as the cell of origin for prostate cancer. Wang ZA, Toivanen R, Bergren SK, Chambon P, Shen MM. Cell Rep. 2014 Sep 11;8(5):1339-46. doi: 10.1016/j.celrep.2014.08.002. Epub 2014 Aug 28. Lineage analysis of basal epithelial cells reveals their unexpected plasticity and supports a cell-of-origin model for prostate cancer heterogeneity. Wang ZA, Mitrofanova A, Bergren SK, Abate-Shen C, Cardiff RD, Califano A, Shen MM. Nat Cell Biol. 2013 Mar;15(3):274-83. doi: 10.1038/ncb2697. Epub 2013 Feb 24. Drosophila follicle stem cells are regulated by proliferation and niche adhesion as well as mitochondria and ROS. Wang ZA, Huang J, Kalderon D. Nat Commun. 2012 Apr 3;3:769. doi: 10.1038/ncomms1765. Revisiting the concept of cancer stem cells in prostate cancer. Wang ZA, Shen MM. Oncogene. 2011 Mar 17;30(11):1261-71. doi: 10.1038/onc.2010.530. Epub 2010 Nov 29. Review.