研究领域

运用果蝇和诱导干细胞作为模型研究神经退行性疾病，尤其是线粒体、核转运、压力颗粒和相分离在渐冻人症和额颞叶认知障碍症发生和发展中的重要作用。此外，我们也通过对病人多组学的分析发现新的药物靶点。

成果

张轲博士在 Nature, Science, Cell, Neuron, Nature Cell Biology 等国际著名期刊上发表研究论文24篇。其中以第一作者或通讯作者发表文章 10 篇（包括Nature 2篇，Cell 1 篇等）。总共引用3000多次，h因子18。先后荣获清华优秀学生奖学金，美国渐冻人症协会Milton Safenowitz Postdoctoral Fellowship (2014)，约翰-霍普金斯医学院Helen B. Taussig Research Award (2016)，Target ALS Foundation Springboard Fellowship （2018）, Frick Foundation for ALS research Award （2020）等荣誉。自从独立开始研究以来，其实验室已获得美国国家卫生院（NIH），美国国防部，以及其他私人基金组织等的基金支持。张轲博士博士期间的研究发现了线粒体在导致神经发育和退行性疾病中脂肪酸代谢异常中的作用，发现了抗氧化剂对线粒体异常导致的神经发育和退行疾病的保护作用，从而为这些疾病提供了新的药物开发方向。其博士后和现在的研究专注于核转运与压力颗粒在渐冻人症和额颞叶认知障碍症中的作用，首次揭示了核转运异常在神经退行性疾病和衰老中的直接作用并为此提供了新的药物开发方向，相关工作被认为是领域内的重大突破。

荣誉

• 2019   Frick渐冻人症基金会，研究奖励

• 2018   Target ALS 基金会，Springboard Fellowship荣誉

• 2016   约翰-霍普金斯医学院Helen B. Taussig 研究奖励

• 2014   美国渐冻人症协会Milton Safenowitz Postdoctoral Fellowship荣誉

代表论文

1. Gao J, Mewborne QT, Girdhar A, Sheth U, Coyne AN, Punathil R, Kang BG, Dasovich M, Veire A, Liu S, Shi Z, Dafinca R, Fouquerel E, Talbot K, Kam T-I, Zhang Y-J, Dickson D, Petrucelli L, Guo L, Dawson TM, Dawson VL, Leung AKL, Lloyd TE, Gendron TF, Rothstein JD, and Zhang K. Poly(ADP-ribose) promotes toxicity of C9ORF72 arginine-rich dipeptide repeat proteins. Science Translational Medicine. 2022, In print

2. Maxwell B, Gwon Y, Mishra A, Peng J, Nakamura H, Zhang K, Kim HJ and Taylor JP. Ubiquitination is essential for recovery of cellular activities following heat shock. Science. 2021;372(6549):eabc3593; DOI: 10.1126/science.abc3593

3. Tang X, Toro A, T G Sahana, Gao J, Chalk J, Oskarsson B, Zhang K. Divergence, Convergence, and Therapeutic Implications: A Cell Biology Perspective of C9ORF72-ALS/FTD. Review. Molecular Neurodegeneration. 2020;15(1):34.

4. Zhang K, Daigle JG, Cunningham KM, Coyne AC, Ruan K, Grima JC, Bowen KE, Wadhwa H, Yang P, Rigo F, Taylor JP, Gitler AD, Rothstein JD, Lloyd TE. Stress granule assembly disrupts nucleocytoplasmic transport, Cell. 2018;173(4):958-971.e17.

5. Zhang K#, Rothstein JD#. Neurodegenerative disease: Two-for-one on potential therapies. Preview. Nature. 2017;544(7650):302-303.

6. Zhang K*, Donnelly CJ*, Haeusler AR, Grima JC, Machamer JB, Steinwald P, Daley EL, Miller SJ, Cunningham KM, Vidensky S, Gupta S, Thomas MA, Hong I, Chiu SL, Huganir RL, Ostrow LW, Matunis MJ, Wang J, Sattler R, Lloyd TE, Rothstein JD. The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature. 2015;525(7567):56-61.

Commented/reported in:

a. Fox and Tibbetts, Nature. 2015;525: 36–7

b. Underwood, Science. 2015 Aug 28;349: 911-2

c. Blitterswijk and Rademakers, Nature Reviews Neurology. 2015;11: 670–2

d. Munteanu and Lynch, Front Neurol. 2016;7: 51

7. Liu L, Zhang K, Sandoval H, Yamamoto S, Jaiswal M, Sanz E, Li Z, Hui J, Graham BH, Quintana A, Bellen HJ. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell. 2015;160(1-2):177-90. 

8. Yamamoto S, Jaiswal M, Charng WL, Gambin T, Karaca E, Mirzaa G, Wiszniewski W, Sandoval H, Haelterman NA, Xiong B, Zhang K, Bayat V, David G, Li T, Chen K, Gala U, Harel T, Pehlivan D, Penney S, Vissers LELM, de Ligt J, Jhangiani SN, Xie Y, Tsang SH, Parman Y, Sivaci M, Battaloglu E, Muzny D, Wan YW, Liu Z, Lin-Moore AT, Clark RD, Curry CJ, Link N, Schulze KL, Boerwinkle E, Dobyns WB, Allikmets R, Gibbs RA, Chen R, Lupski JR, Wangler MF, Bellen HJ. A drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases. Cell. 2014;159(1):200-214. 

9. Zhang K, Li Z, Jaiswal M, Bayat V, Xiong B, Sandoval H, Charng WL, David G, Haueter C, Yamamoto S, Graham BH, Bellen HJ. The C8ORF38 homologue Sicily is a cytosolic chaperone for a mitochondrial complex I subunit. J Cell Biol. 2013;200(6):807-20. 

10. Yamamoto S, Charng WL, Rana NA, Kakuda S, Jaiswal M, Bayat V, Xiong B, Zhang K, Sandoval H, David G, Wang H, Haltiwanger RS, Bellen HJ. A mutation in EGF repeat-8 of Notch discriminates between Serrate/Jagged and Delta family ligands. Science. 2012;338(6111):1229-32.