研究概述
Research Description
伴
随着人口的老龄化，癌症和神经退行性疾病对人类威胁最大的两种疾病。虽然癌症和神经退行性疾病是两种对立的疾病，一个是细胞的过度生长，一个是细胞病例死
亡，但是这两种疾病的引发涉及到许多共同信号通路。我们实验室主要应用果蝇模型探索细胞生长和神经退行性死亡的基本原理，最终帮助人类攻克这些疾病。
1. 雷帕霉素靶蛋白（TOR）通过形成两个结构和功能截然不同的复合物TORC1和TORC2在细胞，组织器官以及整个生物体的生长中起着中心调控的作用。本实验室目前针对TORC1和TORC2的上下游机制，以及在衰老中的调控机制进行研究，目标是建立TOR的信号调控网络，包括TOR对营养，内源激素，生长因子，以及各种外界压力的应答及相互作用。
2. 在
多细胞生物体中，组织的建立以及代谢是通过细胞生长及死亡共同完成的。全面理解神经退化疾病机理不仅利于治疗这类疾病，也为治疗生长相关的疾病比如癌症提
供有效的手段。我们的实验室计划用果蝇模型研究神经退化疾病。我们实验室建立了帕金森氏综合症等几种神经退化疾病的果蝇模型，通过遗传学的手段筛选帕金森
氏综合症的修饰基因，研究线粒体自噬的分子机理，以及致病基因Pink1, Parkin, DJ-1 and LRRK的相互作用，并且在这些神经退化疾病模型中测试药物的效果。
3. 用果蝇模型研究视觉的信号传导通路和视网膜退行性疾病的分子机理，用遗传学和药理学探索视网膜退行性疾病的治疗手段。
Cancer
and Neurodegenerative diseases are two most clinically problematic
classes of disease impacting the world's aging populations. Although
there are apparently opposite phenotypes between cancer cells and
degenerated neurons, common molecular mechanisms might be involved in
dysregulated cancer cell growth and the progression of neurodegenerative
disease. Our laboratory is using Drosophila system to study the
basic molecular mechanisms and crosstalk of cell growth and
neurodegenerative cell death. The ultimate goal of research is to help
cure both diseases. Specifically, research will focus on the following
areas:
1.
Organisms are able to respond appropriately to nutrient flux to
increase their size and cell number so called ‘growth’. Problems in
growth process lead to lots of severe diseases, for example, cancer can
be considered overgrowth of cells. The Target of Rapamycin (TOR) has
central roles in controlling growth of cells, tissues and organisms by
generation of TOR complex 1 (TORC1) and TOR complex 2 (TORC2). We are
using genetic system to learn the basic mechanisms of TORC1 in response
of stress, upstream signals and downstream targets of TORC2 in the cell
growth pathway, and the mechanisms of TOR’s effect on aging. The
ultimate goal of our lab is to establish an entire network of TOR in
response of nutrition, growth factors, hormones and stress.
2.
In metazoans, the coupling of cell growth and cell death together
controls the tissue homeostasis. Understanding neurodegenerative
diseases not only benefits cell death related diseases, but also arises
the treatment option for growth related diseases such as cancer. In our
lab, we are usingDrosophila model to study the pathogenesis of
neurodegenerative diseases especially Parkinson's disease (PD). We are
trying to identify the upstream signal of Pink1 and downstream targets
of Parkin in mitophagy pathway; understand the genetic interaction
between major PD associated genes, Pink1, Parkin, DJ-1 and LRRK; screen
for suppressors of PD animals. In the end, the therapies or drug
targets of PD might be presented.
3.
Retinal degeneration and vision loss is one of the major health
problems, afflicting ~300 millions of people worldwide. However, in
most cases, the underlying mechanisms responsible for retinal
degenerations are still poorly understood, hence have very few effective
treatments. The goals of our research are to exploit Drosophila as a model organism for characterizing the mechanisms underlying
phototransduction and Retinal Degenerations, and to explore strategies
for suppressing these types of neuronal cell death.
发表文章
Publications
1. Wang T.*, Blumhagen R., Lao U. Kuo Y. and Edgar B.A. 2012 LST8 regulates cell growth via Target-of-Rapamycin Complex2. Mol. Cell. Biol. 32(12):2203-2213 (cover article)(* corresponding author)
2. WangX., Wang T., Ni J., Von Lintig J. and Montell C. 2012 The Drosophila visual cycle and de novo chromophore synthesis depends on rdhB. J Neurosci. 32: 3485-3491. (equal contribution of first two authors).
3. Wang X., Wang T., Jiao Y., Von Lintig J. and Montell C. 2010. A visual cycle in Drosophila is mediated by a retinol dehydrogenase, PDH. Curr. Biol. 20:93-102 (equal contribution of first two authors)
4. Wang T., Lao U. and Edgar B.A. 2009. TOR-mediated autophagy regulates cell death in Drosophila neurodegenerative disease. J. Cell Biol. 186: 703-711.
5. Liu Z, Wang X, Yu Y, Li X, Wang T, Jiang H, Ren Q, Jiao Y, Sawa A, Moran T, Ross CA, Montell C, Smith WW. 2008. A Drosophila model for LRRK2-linked parkinsonism. Proc. Natl. Acad. Sci. USA. 105, 2693-2698.
6. Wang T., Wang X., Xie Q. and Montell C. 2008. The SOCS box protein STOPS is required for phototransduction through its effects on phospholipase C. Neuron. 57, 56-68 (Cover article)
7. Wang T. and Montell C. 2007. Phototransduction and retinal degeneration in Drosophila. Pflugers Arch. 454, 821-847. (review)
8. Wang T., Jiao Y. and Montell C. 2007. Dissection of the pathway required for generation of vitamin A and for Drosophila phototransduction. J Cell Biol. 177, 305-316.
9. Liu C-H. Wang T. Postma M. Obukhov A.G. Montell C. and Hardie R.C. 2007. In vivo identification and manipulation of the Ca2+ selectivity filter in the Drosophila TRP channel. J Neurosci. 27, 604-615 (equal contribution of first two authors).
10. Wang T. and Montell C. 2006. A PI Synthase Required for a Sustained Light Response. J Neurosci. 26, 12816-12825.
11. Wang T., Jiao Y. and Montell C. 2005. Dissecting independent channel and scaffolding roles of the Drosophila TRP channel. J. Cell Biol. 171, 685-694.
12. Wang T. and Montell C. 2005. Rhodopsin formation in Drosophila is dependent on the PINTA retinoid binding protein. J. Neurosci. 25, 5187-5194 (Cover article).
13. Wang T., Xu H., Oberwinkler J., Gu Y., Hardie R.C. and Montell C. 2005. Light-activation, adaptation and cell survival functions of the Na+/Ca2+ exchanger, CalX. Neuron 45, 367-378.
Book Chapter:
Wang T. and Edgar B.A. 2010. TOR signaling and cell death. The Enzymes. 28: 217-244.
地址：北京市中关村生命科学园科学园路七号 