Person:
Li, Zhaodong

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Li

First Name

Zhaodong

Name

Li, Zhaodong

Filters

2015 - 20172

Settings

Author's Publications: search.filters.isAuthorOfPublication.e8e108a6-ab50-4775-aeba-6c5f9df93392

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    FTD/ALS-associated poly(GR) protein impairs the Notch pathway and is recruited by poly(GA) into cytoplasmic inclusions
    (Springer Berlin Heidelberg, 2015) Yang, Dejun; Abdallah, Abbas; Li, Zhaodong; Lu, Yubing; Almeida, Sandra; Gao, Fen-Biao
    C9ORF72 repeat expansion is the most common genetic mutation in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Abnormal dipeptide repeat proteins (DPRs) generated from repeat-associated non-AUG (RAN) translation of repeat-containing RNAs are thought to be pathogenic; however, the mechanisms are unknown. Here we report that (GR)80 and (PR)80 are toxic in neuronal and non-neuronal cells in Drosophila. In contrast to reported shorter poly(GR) forms, (GR)80 is mostly localized throughout the cytosol without detectable accumulation in the nucleolus, accompanied by suppression of Notch signaling and cell loss in the wing. Some Notch target genes are also downregulated in brains and iPSC-derived cortical neurons of C9ORF72 patients. Increased Notch expression largely suppressed (GR)80-induced cell loss in the wing. When co-expressed in Drosophila, HeLa cells, or human neurons, (GA)80 recruited (GR)80 into cytoplasmic inclusions, partially decreasing the toxicity of (GR)80 and restoring Notch signaling in Drosophila. Thus, different DPRs have opposing roles in cell loss and we identify the Notch pathway as one of the receptor signaling pathways that might be compromised in C9ORF72 FTD/ALS. Electronic supplementary material The online version of this article (doi:10.1007/s00401-015-1448-6) contains supplementary material, which is available to authorized users.
  • Thumbnail Image
    Publication
    Small genomic insertions form enhancers that misregulate oncogenes
    (Nature Publishing Group, 2017) Abraham, Brian J.; Hnisz, Denes; Weintraub, Abraham S.; Kwiatkowski, Nicholas; Li, Charles H.; Li, Zhaodong; Weichert-Leahey, Nina; Rahman, Sunniyat; Liu, Yu; Etchin, Julia; Li, Benshang; Shen, Shuhong; Lee, Tong Ihn; Zhang, Jinghui; Look, A.; Mansour, Marc R.; Young, Richard A.
    The non-coding regions of tumour cell genomes harbour a considerable fraction of total DNA sequence variation, but the functional contribution of these variants to tumorigenesis is ill-defined. Among these non-coding variants, somatic insertions are among the least well characterized due to challenges with interpreting short-read DNA sequences. Here, using a combination of Chip-seq to enrich enhancer DNA and a computational approach with multiple DNA alignment procedures, we identify enhancer-associated small insertion variants. Among the 102 tumour cell genomes we analyse, small insertions are frequently observed in enhancer DNA sequences near known oncogenes. Further study of one insertion, somatically acquired in primary leukaemia tumour genomes, reveals that it nucleates formation of an active enhancer that drives expression of the LMO2 oncogene. The approach described here to identify enhancer-associated small insertion variants provides a foundation for further study of these abnormalities across human cancers.