Jiou Wang, PhD
Biochemistry and Molecular Biology, Neuroscience
615 N. Wolfe Street
Baltimore , Maryland 21205
PhD , Johns Hopkins School of Medicine , 2002
Mechanisms of Neurodegeneration and Protein Quality Control
Neurodegeneration is a poorly understood biomedical phenomenon and a major public health challenge in our increasingly aging society. Our recent work on an inherited form of Amyotrophic Lateral Sclerosis (ALS), which is caused by mutations in SOD1, has shown that protein misfolding may play a central role in the degeneration of motor neurons. It has become clear that further elucidation of the mechanisms of protein misfolding and quality control in neurons is a critical step toward understanding this form of ALS as well as many other neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s. Our goal is to describe at the molecular and cellular levels how specific neurons degenerate, how protein folding and misfolding operate in the cell, and how protective systems fail at disease stages.
To dissect the complex processes of neurodegeneration, we have established novel C. elegans and mouse models of ALS, which recapitulate major features of the disease, providing a unique avenue for our research. Using the C. elegans model and forward genetic screens, we are searching for key genes and pathways of neurodegeneration that are conserved in humans.
New discoveries of disease genes in humans are accelerating our understanding of the molecular underpinnings of neurodegeneration. We use molecular and cellular, genetic, and biochemical approaches to elucidate how these genes function normally and how mutations lead to disease. The elucidation may ultimately lead to better treatments of these devastating diseases.
Haeusler AR, Donnelly C, Periz G, Simko E, Shaw P, Kim M, Maragakis N, Troncoso J, Pandey A, Sattler R, Rothstein J, and Wang J. (2014) C9orf72 Nucleotide Repeat Structures Initiate Molecular Cascade of Disease. Nature DOI:10.1038/nature13124.
Donnelly CJ, Zhang PW, Pham JT, Haeusler AR, Mistry NA, Vidensky S, Daley EL, Poth EM, Hoover B, Fines DM, Maragakis N, Tienari PJ, Petrucelli L, Traynor BJ, Wang J, Rigo F, Bennett CF, Blackshaw S, Sattler R, Rothstein JD. (2013) RNA toxicity from the ALS/FTD C9ORF72 expansion is mitigated by antisense intervention. Neuron 80: 415-428.
Zhang T, Hwang H.Y., Hao H., Talbot C., Jr., and Wang J. (2012) Caenorhabditis elegans RNA-processing Protein TDP-1 Regulates Protein Homeostasis and Lifespan. J Biol Chem. 287, 8371-8382 (Paper of the Week).
Zhang, T., Mullane, P.C., Periz, G., and Wang, J. (2011). TDP-43 neurotoxicity and protein aggregation modulated by heat shock factor and insulin/IGF-1 signaling. Hum Mol Genet 20, 1952-1965.
Wang J, Farr GW, Hall DH, Futak K, Dreier L, Horwich AL. (2009) An ALS-linked mutant SOD1 produces a locomotor defect associated with aggregation and synaptic dysfunction when expressed in neurons of C. elegans. PLoS Genetics 5(1): e1000350.