个人简介

B.Sc. University of Guelph Ph.D. University of Guelph Postdoc University of Ottawa

研究领域

Non-coding RNA, cellular stress and amyloid aggregation

Noncoding RNAs (ncRNAs) have recently emerged as important regulators of essential cellular pathways. These molecules possess remarkable functional divergence, acting as transcription/translation factors, epigenetic regulators and architectural molecules. In general, ncRNAs are thought to “fine-tune” the basic proteomic machinery and enhance cellular adaptability in response to environmental stressors. Regardless of the stimulus (e.g. heat shock, metabolic deprivation or DNA damage), many ncRNAs facilitate a state of proliferative arrest, allowing the cell to focus its resources on pathways critical to its survival. As the list of functional RNA molecules continues to rapidly expand, it is becoming increasingly clear that the significance and functionality of this family of transcripts may someday rival that of proteins. Our research group studies a newly discovered extracellular stress-response pathway, whereby ncRNAs regulate the rapid and reversible conversion of proteins into amyloid-like structures. Remarkably, these natural amyloids possess most of the biochemical properties associated with the plaques and aggregates observed in Alzheimer’s, Parkinson’s and prion-based diseases, suggesting that dysregulation of this biological pathway could be a common cause of many neurodegenerative disorders. We are focused on identifying the environmental and cellular factors that mediate the formation and disassembly of these natural amyloid aggregates, while considering the translational significance of this work to prevent and treat neurological diseases.

近期论文

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Audas TE, Audas DE, Jacob MD, Ho JJ, Khacho M, Wang M, Perera JK, Gardiner C, Bennett CA, Head T, Kryvenko ON, Jorda M, Daunert S, Malhotra A, Trinkle-Mulcahy L, Gonzalgo ML, Lee S. Adaptation to Stressors by Systemic Protein Amyloidogenesis. Dev Cell. 2016 Oct 24;39(2):155-168. doi: 10.1016/j.devcel.2016.09.002. Audas TE, Lee S. Stressing out over long noncoding RNA. Biochim Biophys Acta. 2016 Jan;1859(1):184-91. doi: 10.1016/j.bbagrm.2015.06.010. Epub 2015 Jul 2. Review. Jacob MD, Audas TE, Uniacke J, Trinkle-Mulcahy L, Lee S. Environmental cues induce a long noncoding RNA-dependent remodeling of the nucleolus. Mol Biol Cell. 2013 Sep;24(18):2943-53. doi: 10.1091/mbc.E13-04-0223. Epub 2013 Jul 31. Audas TE, Jacob MD, Lee S. Immobilization of proteins in the nucleolus by ribosomal intergenic spacer noncoding RNA. Mol Cell. 2012 Jan 27;45(2):147-57. doi: 10.1016/j.molcel.2011.12.012.