郑辉

郑辉博士在老年痴呆症（AD）研究领域积极活跃了15年之久，成为该领域的国际知名专家。她最初在默克公司工作，随后加入贝勒医学院，成为该院终身正教授。近期，她还被任命为Huffington衰老研究中心主任。

郑辉博士最早使用转基因和基因敲除技术鉴定出AD相关基因——β-淀粉样前体蛋白（APP）和早老素（PS1和PS2）。在此基础上，她实验室中建立了大量AD相关小鼠模型。由于这些基因的突变可引发早发性老年痴呆症，她的工作不仅对理解疾病机制具有关键意义，还为药物开发提供了宝贵的动物模型。

在科研产出方面，郑辉博士发表了60余篇论文，大部分刊载于Cell、Nature、Neuron和PNAS等顶级刊物。她获得了多项荣誉，包括美国老年痴呆症协会授予的Zenith奖以及Ellision医学基金授予的New Scholar奖。

郑辉博士目前担任美国国家衰老研究院神经科学衰老研究常务委员会的主席，体现了她在该领域的领导地位和学术权威。

以下为郑辉博士的部分代表性论文：

• Li H, Wang B, Wang Z, Guo Q, Tabuchi K, Hammer RE, Südhof TC, Zheng H (2010). Soluble amyloid precursor protein (APP) regulates transthyretin and Klotho gene expression without rescuing the essential function of APP. Proc. Natl. Acad. Sci. U S A 107(40): 17362-7.
• Li H, Wang Z, Wang B, Guo Q, Dolios G, Tabuchi K, Hammer RE, Südhof TC, Wang R, Zheng H (2010). Genetic dissection of the amyloid precursor protein in developmental function and amyloid pathogenesis. J. Biol. Chem. 285(40): 30598-605.
• Yang L, Wang Z, Wang B, Justice NJ, Zheng H (2009). Amyloid precursor protein regulates Cav1.2 L-type calcium channel levels and function to influence GABAergic short-term plasticity. J. Neurosci. 29(50): 15660-8.
• Wang Z, Wang B, Yang L, Guo Q, Aithmitti N, Songyang Z, Zheng H (2009). Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis. J. Neurosci. 29(35): 10788-801.
• Kallhoff-Munoz V, Hu L, Chen X, Pautler RG, Zheng H (2008). Genetic dissection of γ-secretase-dependent and -independent functions of presenilin in regulating neuronal cell cycle and cell death. J. Neurosci. 28(44): 11421-31.
• Wang B, Yang L, Wang Z, Zheng H (2007). Amyloid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter. Proc. Natl. Acad. Sci. U S A 104(35): 14140-5.
• Wang R, Wang B, He W, Zheng H (2006). Wild-type presenilin protects against Alzheimer’s disease mutation-induced amyloid pathology. J. Biol. Chem. 281(22): 15330-6.
• Deng Y, Tarassishin L, Kallhoff V, Peethumnongsin E, Wu L, Li Y, Zheng H (2006). Deletion of presenilin 1 hydrophilic loop sequence leads to impaired gamma-secretase activity and exacerbated amyloid pathology. J. Neurosci. 26(14): 3845-54.
• Wang R, Tang P, Wang P, Boissy RE, Zheng H (2006). Regulation of tyrosinase trafficking and processing by presenilins: Partial loss of function by familial Alzheimer’s disease mutation. Proc. Natl. Acad. Sci. U S A 103(2): 353-8.
• Wang P, Yang G, Mosier DR, Chang P, Zaidi T, Gong YD, Zhao NM, Dominguez B, Lee KF, Gan WB, Zheng H (2005). Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-like protein 2. J. Neurosci. 25(5): 1219-25.
• Wang P, Pereira FA, Beasley D, Zheng H (2003). Presenilins are required for the formation of comma- and S-shaped bodies during nephrogenesis. Development 130(20): 5019-29.
• Kang DE, Soriano S, Xia X, Eberhart CG, De Strooper B, Zheng H, Koo EH (2002). Presenilin couples the paired phosphorylation of beta-catenin independent of axin: implications for beta-catenin activation in tumorigenesis. Cell 110(6): 751-62.
• Xia X, Wang P, Sun X, Soriano S, Shum WK, Trumbauer ME, Takashima A, Koo EH, Zheng H (2002). The aspartate-257 of presenilin 1 is indispensable for mouse development and production of β-amyloid peptides through β-catenin independent mechanisms. Proc. Natl. Acad. Sci. U S A 99(13): 8760-8765.
• Xia X, Qian S, Soriano S, Wu Y, Fletcher A, Wang XJ, Koo EH, Wu X, Zheng H (2001). Loss of presenilin 1 is associated with enhanced β-catenin signaling and skin tumorigenesis. Proc. Natl. Acad. Sci. U S A 98(19): 10863-10868.

郑辉博士的研究为理解阿尔茨海默病的分子机制做出了重要贡献，尤其是通过转基因和基因敲除技术鉴定了关键致病基因，并建立了宝贵的动物模型。她的工作不仅推动了基础研究，也为药物开发提供了重要平台。未来，郑辉博士的团队将继续探索APP和早老素在神经退行性疾病中的功能，以及开发新的治疗策略。

• Li H, Wang B, Wang Z, Guo Q, Tabuchi K, Hammer RE, Südhof TC, Zheng H. Soluble amyloid precursor protein (APP) regulates transthyretin and Klotho gene expression without rescuing the essential function of APP. Proc Natl Acad Sci U S A. 2010;107(40):17362-7.
• Li H, Wang Z, Wang B, Guo Q, Dolios G, Tabuchi K, Hammer RE, Südhof TC, Wang R, Zheng H. Genetic dissection of the amyloid precursor protein in developmental function and amyloid pathogenesis. J Biol Chem. 2010;285(40):30598-605.
• Yang L, Wang Z, Wang B, Justice NJ, Zheng H. Amyloid precursor protein regulates Cav1.2 L-type calcium channel levels and function to influence GABAergic short-term plasticity. J Neurosci. 2009;29(50):15660-8.
• Wang Z, Wang B, Yang L, Guo Q, Aithmitti N, Songyang Z, Zheng H. Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis. J Neurosci. 2009;29(35):10788-801.
• Kallhoff-Munoz V, Hu L, Chen X, Pautler RG, Zheng H. Genetic dissection of γ-secretase-dependent and -independent functions of presenilin in regulating neuronal cell cycle and cell death. J Neurosci. 2008;28(44):11421-31.
• Wang B, Yang L, Wang Z, Zheng H. Amyloid precursor protein mediates presynaptic localization and activity of the high-affinity choline transporter. Proc Natl Acad Sci U S A. 2007;104(35):14140-5.
• Wang R, Wang B, He W, Zheng H. Wild-type presenilin protects against Alzheimer’s disease mutation-induced amyloid pathology. J Biol Chem. 2006;281(22):15330-6.
• Deng Y, Tarassishin L, Kallhoff V, Peethumnongsin E, Wu L, Li Y, Zheng H. Deletion of presenilin 1 hydrophilic loop sequence leads to impaired gamma-secretase activity and exacerbated amyloid pathology. J Neurosci. 2006;26(14):3845-54.
• Wang R, Tang P, Wang P, Boissy RE, Zheng H. Regulation of tyrosinase trafficking and processing by presenilins: Partial loss of function by familial Alzheimer’s disease mutation. Proc Natl Acad Sci U S A. 2006;103(2):353-8.
• Wang P, Yang G, Mosier DR, Chang P, Zaidi T, Gong YD, Zhao NM, Dominguez B, Lee KF, Gan WB, Zheng H. Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-like protein 2. J Neurosci. 2005;25(5):1219-25.
• Wang P, Pereira FA, Beasley D, Zheng H. Presenilins are required for the formation of comma- and S-shaped bodies during nephrogenesis. Development. 2003;130(20):5019-29.
• Kang DE, Soriano S, Xia X, Eberhart CG, De Strooper B, Zheng H, Koo EH. Presenilin couples the paired phosphorylation of beta-catenin independent of axin: implications for beta-catenin activation in tumorigenesis. Cell. 2002;110(6):751-62.
• Xia X, Wang P, Sun X, Soriano S, Shum WK, Trumbauer ME, Takashima A, Koo EH, Zheng H. The aspartate-257 of presenilin 1 is indispensable for mouse development and production of β-amyloid peptides through β-catenin independent mechanisms. Proc Natl Acad Sci U S A. 2002;99(13):8760-5.
• Xia X, Qian S, Soriano S, Wu Y, Fletcher A, Wang XJ, Koo EH, Wu X, Zheng H. Loss of presenilin 1 is associated with enhanced β-catenin signaling and skin tumorigenesis. Proc Natl Acad Sci U S A. 2001;98(19):10863-8.
• Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Mol Med. 2016;8(6):595-608.
• Shen J, Kelleher RJ 3rd. The presenilin hypothesis of Alzheimer's disease: evidence for a loss-of-function pathogenic mechanism. Proc Natl Acad Sci U S A. 2007;104(2):403-9.
• Jiang H, Poirier M, Liang Y, et al. Depletion of C9orf72 reduces dipeptide repeat protein levels and ameliorates neurodegeneration in C9ALS/FTD mice. Nat Neurosci. 2019;22(1):55-64.
• 周瑾, 王建枝. 阿尔茨海默病的β-淀粉样蛋白级联假说. 中国神经精神疾病杂志. 2005;31(3):239-41.