徐进
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| 徐进 |
徐进博士先就读于湖南医科大学英语医学班，随后于美国东南路易斯安娜州大获生物学学士学位。1998年于Tulane大学获分子细胞生物学博士学位。1998-2003期间，在哈佛医学院Bruce Yankner实验室进行博士后研究。自2003年7月，徐进作为研究组长任职于波士顿圣伊莉沙白医学中心，Tufts大学医学院神经系。2010年8月加入中科院神经科学研究所，担任研究员和神经退行性疾病基理研究组组长，主要从事帕金森氏及相关疾病的机理研究。
研究方向
帕金森氏病（PD）是最常见的运动神经疾病。仅在中国，至少一百五十多万病人受此神经退行性疾病困扰。PD是由多巴胺神经元的退化造成，导致病人行动障碍。目前治疗措施局限于症状控制，而无法根治。不过近来在PD遗传机理方面的进展给了我们新的线索。我们研究组的长远目标是进一步地认识PD致病机理，从而更有效地预防，诊断和治疗帕金森氏病及相关疾病。目前，我们对以下几方面的研究感兴趣：
表观遗传学和PD的相关性
尽管有数个与PD相关的基因被发现，多数晚发型的PD病例与致病基因突变并未联系。人口老年化是散发性PD最主要的致病因素。我们先前对PD关联的蛋白功能研究揭示了表观遗传学在晚发型PD病生中的潜在作用。所以，我们正运用分子，细胞学和生物信息的方法来进一步研究表观遗传学和PD的相关性。
对PD关联的蛋白的功能研究
至今α-synuclein, Parkin, DJ-1, PINK-1和LRRK2已被确认为与PD相关蛋白。对这些蛋白的功能的研究会帮助我们更深一步地阐明PD的分子机理，辨别造成神经功能紊乱和多巴胺神经元退化的分子途径。鉴于衰老是散发性PD最主要的致病因素，我们也将研究衰老与PD关联的蛋白的潜在分子作用。
探索对PD的创新治疗方法
在过去几年中，我们对疾病机理的研究显示了两组物质能弥补由DJ-1的缺陷造成的功能失调。一组物质包括组蛋白乙酰化刺激因子和转录调控因子；另一组物质包括线粒体功能激活因子。所以，我们将会筛选针对这两方面作用的特异且强效的物质，并在细胞及动物模型中检测它们的功效。
代表性论文
1. Shtifman, A., Zhong, N., Lopez, J., Shen, J., and Xu, J. (2009) Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice. Neurobiol. Aging in press. (Available online Aug 14, 2009).
2. Zhong, N., and Xu, J. (2008) Synergistic activation of the human MnSOD promoter by DJ-1 and PGC-1alpha: regulation by SUMOylation and oxidation. Hum. Mol. Genet. 17: 3357-3367.
3. Zhong, N., Kim, C., Rizzu, P., Geula, C., Porter, D., Pothos, E., Squitieri, F., Heutink, P., and Xu, J. (2006) DJ-1 transcriptionally up-regulates the human tyrosine hydroxylase by inhibiting the sumoylation of pyrimidine tract-binding protein-associated splicing factor. J. Biol. Chem. 281: 20940-20948.
4. Xu, J.*, Zhong, N, Wang, H., Elias, J., Kim, C., Woldman, I., Pifl, C., Gygi, S., Geula, C., and Yankner, B. (2005) The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis. Hum. Mol. Genet. 14: 1231-1241. * Corresponding author.
5. Shan, B., Xu, J., Zhuo, Y., Morris, C., and Morris, G. (2003) Induction of p53-dependent activation of the human proliferating cell nuclear antigen gene in chromatin by ionizing radiation. J. Biol. Chem. 278: 44009-44017.
6. Xu, J., Kao, S., Lee, F., Song, W., Jin, L., and Yankner, B. (2002) Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat. Med. 8: 600-606. Featured on the cover; News and View by Junyin Yuan.
7. Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B., and Yuan, J. (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403: 98-103.
8. Xu, J., and Morris, G. (1999) p53-mediated regulation of proliferating cell nuclear antigen expression in cells exposed to ionizing radiation. Mol. Cell Biol. 19: 12-20.
1. Shtifman, A., Zhong, N., Lopez, J., Shen, J., and Xu, J. (2009) Altered Ca2+ homeostasis in the skeletal muscle of DJ-1 null mice. Neurobiol. Aging in press. (Available online Aug 14, 2009).
2. Zhong, N., and Xu, J. (2008) Synergistic activation of the human MnSOD promoter by DJ-1 and PGC-1alpha: regulation by SUMOylation and oxidation. Hum. Mol. Genet. 17: 3357-3367.
3. Zhong, N., Kim, C., Rizzu, P., Geula, C., Porter, D., Pothos, E., Squitieri, F., Heutink, P., and Xu, J. (2006) DJ-1 transcriptionally up-regulates the human tyrosine hydroxylase by inhibiting the sumoylation of pyrimidine tract-binding protein-associated splicing factor. J. Biol. Chem. 281: 20940-20948.
4. Xu, J.*, Zhong, N, Wang, H., Elias, J., Kim, C., Woldman, I., Pifl, C., Gygi, S., Geula, C., and Yankner, B. (2005) The Parkinson's disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis. Hum. Mol. Genet. 14: 1231-1241. * Corresponding author.
5. Shan, B., Xu, J., Zhuo, Y., Morris, C., and Morris, G. (2003) Induction of p53-dependent activation of the human proliferating cell nuclear antigen gene in chromatin by ionizing radiation. J. Biol. Chem. 278: 44009-44017.
6. Xu, J., Kao, S., Lee, F., Song, W., Jin, L., and Yankner, B. (2002) Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat. Med. 8: 600-606. Featured on the cover; News and View by Junyin Yuan.
7. Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B., and Yuan, J. (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403: 98-103.
8. Xu, J., and Morris, G. (1999) p53-mediated regulation of proliferating cell nuclear antigen expression in cells exposed to ionizing radiation. Mol. Cell Biol. 19: 12-20.
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