Amyotrophic lateral sclerosis; protein quality control; RNA metabolism
Experiences & Accomplishments
University of Science and Technology of China
Amyotrophic lateral sclerosis (ALS) is characterized by the degeneration of both upper and lower motor neurons, which leads to muscle weakness and eventually paralysis. Mutations in genes causing ALS include SOD1, FUS/TLS, TDP-43, OPTN, VAPB, VCP, UBQLN2, PFN1, MATR3, SQSTM1 and C9ORF72. Among ALS associated proteins, TDP-43 and FUS are RNA-binding proteins that form aggregates in ALS and FTLD, and when mutated can drive the pathogenesis of these disorders. Protein and RNA homeostasis are two major themes in the studies of neurodegenerative diseases including ALS/FTLD. Protein quality control has an important regulatory role in cellular function. RNA metabolism incudes a series of distinct processes including RNA splicing, transport and stability, as well as the biogenesis of non-coding small RNAs. My work is focusing on the interplay between the protein- and RNA-based mechanisms driving the dysregulated cellular processes in ALS/FTLD, which provides new perspectives on pathogenesis and intervention.
Honors & Awards
2020 Cozzarelli Prize (Journal of PNAS) 2019 Lawrence Grossman Achievement Award, Johns Hopkins University, USA 2012 Janssen Fellowship Award, Johns Hopkins University, USA
- Zhang T*, Periz G*, Lu Y, Wang J. (2020) USP7 regulates ALS-associated proteotoxicity and quality control through the NEDD4L-SMAD pathway. Proc Natl Acad Sci USA 117(45):28114-28125.
- Zhang T*, Wu Y*, Mullane P, Ji Y, Liu H, He L, Arora A, Hwang H, Alessi A, Miaki A, Periz G, Guo L, Wang H, Elkayam E, Joshua-Tor L, Myong S, Kim J, Shorter J, Ong S, Leung A, Wang J. (2018) FUS Regulates Activity of MicroRNA-mediated Gene Silencing. Molecular Cell 69:1-15.
- Zhang T, Baldie G, Periz G, Wang J. RNA-processing protein TDP-43 regulates FOXO-dependent protein quality control in stress response. PLoS Genet. 2014 Oct 16;10(10):e1004693.
- Zhang T, Hwang HY, Hao H, Talbot C Jr, Wang J. Caenorhabditis elegans RNA-processing protein TDP-1 regulates protein homeostasis and life span. J Biol Chem. 287(11): 8371-82, 2012.
- Zhang T*, Mullane PC*, Periz G, Wang J. TDP-43 neurotoxicity and protein aggregation modulated by heat shock factor and insulin/IGF-1 signaling. Hum Mol Genet. 20(10): 1952-65, 2011.