• Source: Zhenyu Yue

Zhenyu Yue is a Chinese academic researcher in the field of neurology and neuroscience, who is the Alex and Shirley Aidekman Professor at the Icahn School of Medicine at Mount Sinai, New York. He is known for his discovery of genes controlling autophagy (cell self-eating), autophagy functions in central nervous system, molecular mechanism of neurodegenerative diseases, and modelling neurological diseases using genetic mouse models.




Early life and education


Zhenyu Yue earned a Bachelor of Science (B.S.) degree in Cell Biology from Wuhan University in China in 1988. He then obtained a Master of Science (M.S.) degree in Vertebrate Genetics from the Institute of Hydrobiology at the Chinese Academy of Science, also in Wuhan, China, in 1991. In pursuit of further education, Yue relocated to the United States, where he embarked on doctoral studies in Molecular Biology and Biochemistry. He conducted his Ph.D. research under the mentorship of Aaron J Shatkin, a member of the National Academy of Sciences, at UMDNJ-Rutgers, Robert Wood Johnson Medical School in New Jersey. His doctoral studies, which spanned from 1992 to 1997, focused on virus biology and mRNA modifications. The highlight of this Ph.D. thesis is the identification of human mRNA capping enzyme, which is a significant contribution to the understanding of mRNA biology, and has yielded the patent “mRNA Capping and Use thereof”.
Yue engaged in postdoctoral research at the Howard Hughes Medical Institute/The Rockefeller University in New York. From 1998 to 2002, he worked under the guidance of Nathaniel Heintz, specializing in molecular biology and neuroscience. He reported the first autophagy gene disruption mouse models, which revealed a link of autophagy to tumorigenesis. Yue pioneered autophagy research in neurodegeneration using Lurcher mice.




Research and career


Zhenyu Yue's research has primarily concentrated on the molecular and cellular mechanisms underlying neurodegenerative diseases, with a particular focus on Parkinson’s disease and Alzheimer’s disease.
One of the notable areas of Yue's research involves the study of autophagy, a cellular process that degrades and recycles cellular components. His work has led to the identification of novel autophagy regulators, such as the components in Beclin 1-hVPS34 complex (class 3 PI3K), Atg14L, Rubicon, and NRBF2, which play crucial roles in the autophagy pathway. This research is significant for understanding how disruptions in cellular cleaning mechanisms can contribute to the development of neurodegenerative diseases.
Yue's research has contributed to identifying and characterizing autophagy receptors, which are implicated in neurodegenerative diseases and psychiatric disorders. For instance, SQSTM1/p62, often found in Lewy bodies, tau tangles, and huntingtin aggregates, is the prototype of autophagy receptor that regulates the clearance of polyubiquitinated protein complex and aggregate through autophagy. AKAP11, a significant risk gene for bipolar and schizophrenia, is an autophagy receptor that control PKA-RI complex degradation through autophagy.
Yue's research has extended to identifying and characterizing therapeutic targets for Parkinson’s disease (PD). For instance, he has explored the role of LRRK2 and synaptojanin 1 signalling pathway in neurodegeneration. Yue’s investigation demonstrated that vitamin B12 modulates LRRK2 kinase activity through allosteric regulation and confers neuroprotection. Furthermore, Yue’s group has performed molecular profiling of substant nigra from the PD post-mortem brains using single nucleus RNA sequencing, and identified diverse dopamine neuron subpopulations and a novel vulnerable neuron type. His studies provided valuable resource and insight into therapeutic targets of PD.
After concluding his postdoctoral tenure at The Rockefeller University in New York, Yue joined the Mount Sinai School of Medicine in New York in August 2004 as an assistant professor in the Department of Neurology & Neuroscience. He was promoted to associate professor with tenure in August 2008, and then full Professor of Neurology and Neuroscience in July 2013.
Yue has been the Director of Basic and Translational Research in Movement Disorders since December 2012 and Director of the Center for Parkinson’s Disease Neurobiology since July 2022.




Awards



In 2008, Yue was honored with the Faculty Council Award for Academic Excellence by Mount Sinai.
Yue holds the Alex and Shirley Aidekman Family Neurological Research Professorship at Mount Sinai.
Yue has been a recipient of the Sundaram Research Scholar Award from the Mount Sinai Medical Center in 2017, 2018, and 2019.
Yue has been a member of Sigma Xi, The Scientific Research Honor Society, since March 2024.
In addition to his institutional honors, Yue has been actively involved with the Chinese Biological Investigator Society (CBIS), serving as a board member since 2016.




Selected publications


Yue, Z.; Maldonado, E.; Pillutla, R.; Cho, H.; Reinberg, D.; Shatkin, A. J. (1997-11-25). "Mammalian capping enzyme complements mutant Saccharomyces cerevisiae lacking mRNA guanylyltransferase and selectively binds the elongating form of RNA polymerase II". Proceedings of the National Academy of Sciences of the United States of America. 94 (24): 12898–12903. Bibcode:1997PNAS...9412898Y. doi:10.1073/pnas.94.24.12898. ISSN 0027-8424. PMC 24235. PMID 9371772.
Yue, Zhenyu; Horton, Antony; Bravin, Monica; DeJager, Philip L.; Selimi, Fekrije; Heintz, Nathaniel (2002-08-29). "A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice". Neuron. 35 (5): 921–933. doi:10.1016/s0896-6273(02)00861-9. ISSN 0896-6273. PMID 12372286.
Yue, Zhenyu; Jin, Shengkan; Yang, Chingwen; Levine, Arnold J.; Heintz, Nathaniel (2003-12-09). "Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor". Proceedings of the National Academy of Sciences of the United States of America. 100 (25): 15077–15082. Bibcode:2003PNAS..10015077Y. doi:10.1073/pnas.2436255100. ISSN 0027-8424. PMC 299911. PMID 14657337.
Komatsu, Masaaki; Waguri, Satoshi; Koike, Masato; Sou, Yu-Shin; Ueno, Takashi; Hara, Taichi; Mizushima, Noboru; Iwata, Jun-Ichi; Ezaki, Junji; Murata, Shigeo; Hamazaki, Jun; Nishito, Yasumasa; Iemura, Shun-Ichiro; Natsume, Tohru; Yanagawa, Toru (2007-12-14). "Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice". Cell. 131 (6): 1149–1163. doi:10.1016/j.cell.2007.10.035. ISSN 0092-8674. PMID 18083104.
Zhong, Yun; Wang, Qing Jun; Li, Xianting; Yan, Ying; Backer, Jonathan M.; Chait, Brian T.; Heintz, Nathaniel; Yue, Zhenyu (April 2009). "Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex". Nature Cell Biology. 11 (4): 468–476. doi:10.1038/ncb1854. ISSN 1476-4679. PMC 2664389. PMID 19270693.
Li, Xianting; Patel, Jyoti C.; Wang, Jing; Avshalumov, Marat V.; Nicholson, Charles; Buxbaum, Joseph D.; Elder, Gregory A.; Rice, Margaret E.; Yue, Zhenyu (2010-02-03). "Enhanced Striatal Dopamine Transmission and Motor Performance with LRRK2 Overexpression in Mice Is Eliminated by Familial Parkinson's Disease Mutation G2019S". The Journal of Neuroscience. 30 (5): 1788–1797. doi:10.1523/JNEUROSCI.5604-09.2010. ISSN 0270-6474. PMC 2858426. PMID 20130188.
Lu, Jiahong; He, Liqiang; Behrends, Christian; Araki, Masatake; Araki, Kimi; Jun Wang, Qing; Catanzaro, Joseph M.; Friedman, Scott L.; Zong, Wei-Xing; Fiel, M. Isabel; Li, Min; Yue, Zhenyu (2014-05-22). "NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity". Nature Communications. 5: 3920. Bibcode:2014NatCo...5.3920L. doi:10.1038/ncomms4920. ISSN 2041-1723. PMC 4376476. PMID 24849286.
Grapin, C. (1989). "[Treatment of anomalies associated with ectopies]". Chirurgie Pédiatrique. 30 (3): 164. ISSN 0180-5738. PMID 2572348.
Wold, Mitchell S.; Lim, Junghyun; Lachance, Véronik; Deng, Zhiqiang; Yue, Zhenyu (2016-12-09). "ULK1-mediated phosphorylation of ATG14 promotes autophagy and is impaired in Huntington's disease models". Molecular Neurodegeneration. 11 (1): 76. doi:10.1186/s13024-016-0141-0. ISSN 1750-1326. PMC 5148922. PMID 27938392.
Pan, Ping-Yue; Li, Xianting; Wang, Jing; Powell, James; Wang, Qian; Zhang, Yuanxi; Chen, Zhaoyu; Wicinski, Bridget; Hof, Patrick; Ryan, Timothy A.; Yue, Zhenyu (2017-11-22). "Parkinson's Disease-Associated LRRK2 Hyperactive Kinase Mutant Disrupts Synaptic Vesicle Trafficking in Ventral Midbrain Neurons". The Journal of Neuroscience. 37 (47): 11366–11376. doi:10.1523/JNEUROSCI.0964-17.2017. ISSN 1529-2401. PMC 5700420. PMID 29054882.
Schaffner, Adam; Li, Xianting; Gomez-Llorente, Yacob; Leandrou, Emmanouela; Memou, Anna; Clemente, Nicolina; Yao, Chen; Afsari, Farinaz; Zhi, Lianteng; Pan, Nina; Morohashi, Keita; Hua, Xiaoluan; Zhou, Ming-Ming; Wang, Chunyu; Zhang, Hui (April 2019). "Vitamin B12 modulates Parkinson's disease LRRK2 kinase activity through allosteric regulation and confers neuroprotection". Cell Research. 29 (4): 313–329. doi:10.1038/s41422-019-0153-8. ISSN 1748-7838. PMC 6462009. PMID 30858560.
Deng, Zhiqiang; Lim, Junghyun; Wang, Qian; Purtell, Kerry; Wu, Shuai; Palomo, Gloria M.; Tan, Haiyan; Manfredi, Giovanni; Zhao, Yanxiang; Peng, Junmin; Hu, Bo; Chen, Shi; Yue, Zhenyu (May 2020). "ALS-FTLD-linked mutations of SQSTM1/p62 disrupt selective autophagy and NFE2L2/NRF2 anti-oxidative stress pathway". Autophagy. 16 (5): 917–931. doi:10.1080/15548627.2019.1644076. ISSN 1554-8635. PMC 7144840. PMID 31362587.
Deng, Zhiqiang; Li, Xianting; Blanca Ramirez, Marian; Purtell, Kerry; Choi, Insup; Lu, Jia-Hong; Yu, Qin; Yue, Zhenyu (2021-04-06). "Selective autophagy of AKAP11 activates cAMP/PKA to fuel mitochondrial metabolism and tumor cell growth". Proceedings of the National Academy of Sciences of the United States of America. 118 (14): e2020215118. Bibcode:2021PNAS..11820215D. doi:10.1073/pnas.2020215118. ISSN 1091-6490. PMC 8040602. PMID 33785595.
Choi, Insup; Wang, Minghui; Yoo, Seungyeul; Xu, Peng; Seegobin, Steven P.; Li, Xianting; Han, Xian; Wang, Qian; Peng, Junmin; Zhang, Bin; Yue, Zhenyu (July 2023). "Autophagy enables microglia to engage amyloid plaques and prevents microglial senescence". Nature Cell Biology. 25 (7): 963–974. doi:10.1038/s41556-023-01158-0. ISSN 1476-4679. PMC 10950302. PMID 37231161.
Rolak, L. A. (October 1987). "Copolymer-I therapy for multiple sclerosis". Clinical Neuropharmacology. 10 (5): 389–396. doi:10.1097/00002826-198710000-00001. ISSN 0362-5664. PMID 2972360.
Zhou, Xiaoting; Lee, You-Kyung; Li, Xianting; Kim, Henry; Sanchez-Priego, Carlos; Han, Xian; Tan, Haiyan; Zhou, Suiping; Fu, Yingxue (2022-12-04), Integrated proteomics reveals the landscape of autophagy degradation in human neurons and autophagy receptors regulating neuronal activity, doi:10.1101/2022.12.04.519029, retrieved 2024-04-28




Personal life


Yue has been married to Yuko Kawai. They have two children.




References






External links


Yue Laboratory's website
Google Scholar profile for Zhenyu Yue

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