Wang Laboratory

Genomic stability

Our Aim

Our Interest

Our Team

Our Projects

1. The function of DNA damage response [e.g. DNA repair pathways, cell cycle checkpoint and cell death] in cell fate determination, tissue homeostasis and pathogenesis, focusing on its impact on neuro(de)generation, as well as on cancer development.
2. The homeostasis of poly(ADP-ribosyl)ation in the repair of DNA replication fork damage, cell cycle checkpoint, and in cellular and mouse models.
3. The DNA damage response and epigenetic modification in the maintenance and ageing of stem cells.

Our Favourite Genes:

PARP1, PARG, NBS1, ATM, ATR, TopBP1, CHK1, MCPH1, TRRAP

Our Tools

1. Cellular and molecular studies:
   • DNA damage response and repair assays (Western blotting, DRGFP assay, live cell imaging, immunofluorescence analysis, cell imaging, etc.)
   • Cell cycle checkpoint activation and cell cycle progression
   • DNA replication assays
   • Poly(ADP-ribosyl)ation assays
   • Protein-protein interaction and dynamics
   • Epigenetic and post-translational modifications
   • ShRNA and siRNA knockdown in various cell types
   • Chromatin immuno-precipitation (ChIP)
   • Apoptosis and necrosis assays
   • ES cell differentiation in vivo and in vitro
2. Neurogenesis analyses in vitro and in vivo:
   • In vitro neurosphere cultures
   • In vivo neuroprogenitor cell cycle assays
   • DNA damage and repair assays in vivo
   • Live cell imaging of neocortical cultures and cells
   • In utero electroporations and gene manipulations
   • Organotypic culture
3. Mouse genetics and modelling:
   • Conventional and conditional (or inducible) gene targeting in ES cells and other cell types
   • Generation and characterisation of knock-out, knock-in and transgenic mouse models
   • Oocyte injection, blastocyst injection, morula aggregation
   • Bone marrow transplantation
   • Histopathological analysis of animal models

Selected publications

• Zhou Z, Bruhn C, Wang ZQ (2012) Differential function of NBS1 and ATR in neurogenesis. DNA Repair (Amst), 11, 210-221. [PubMed]
• Li R, Yang YG, Gao Y, Wang ZQ, Tong WM (2012) A distinct response to endogenous DNA damage in the development of Nbs1-deficient cortical neurons. Cell Res, epub ahead of print. [PubMed]
• Gruber R, Zhou Z, Sukchev M, Joerss T, Frappart PO, Wang ZQ (2011) MCPH1 regulates the neuroprogenitor division mode by coupling the centrosomal cycle with mitotic entry through the Chk1-Cdc25 pathway. Nat Cell Biol, 13, 1325-1334. [PubMed]
• Gatz SA, Ju L, Gruber R, Hoffmann E, Carr AM, Wang ZQ, Liu C, Jeggo PA (2011) Requirement for DNA ligase IV during embryonic neuronal development. J Neurosci, 31, 10088-10100. [PubMed]
• Saidi A, Li T, Weih F, Concannon P, Wang ZQ (2010) Dual functions of Nbs1 in the repair of DNA breaks and proliferation ensure proper V(D)J recombination and T-cell development. Mol Cell Biol, 30, 5572-5581. [PubMed]
• Min W, Cortes U, Herceg Z, Tong WM, Wang ZQ (2010) Deletion of the nuclear isoform of poly(ADP-ribose) glycohydrolase (PARG) reveals its function in DNA repair, genomic stability and tumorigenesis. Carcinogenesis, 31, 2058-2065. [PubMed]
• Min W, Wang ZQ (2009) Poly(ADP-ribose) glycohydrolase (PARG) and its therapeutic potential. Front Biosci, 14, 1619-1626. [PubMed]
• Murr R, Loizou JI, Yang YG, Cuenin C, Li H, Wang ZQ, Herceg Z (2006) Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks. Nat Cell Biol, 8, 91-99. [PubMed]
• Yang YG, Saidi A, Frappart PO, Min W, Barrucand C, Dumon-Jones V, Michelon J, Herceg Z, Wang ZQ (2006) Conditional deletion of Nbs1 in murine cells reveals its role in branching repair pathways of DNA double-strand breaks. EMBO J, 25, 5527-5538. [PubMed]
• Frappart PO, Tong WM, Demuth I, Radovanovic I, Herceg Z, Aguzzi A, Digweed M, Wang ZQ (2005) An essential function for NBS1 in the prevention of ataxia and cerebellar defects. Nat Med, 11, 538-544. [PubMed]
• Nakanishi K, Yang YG, Pierce AJ, Taniguchi T, Digweed M, D'Andrea AD, Wang ZQ, Jasin M (2005) Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair. Proc Natl Acad Sci USA, 102, 1110-1115. [PubMed]
• Dumon-Jones V, Frappart PO, Tong WM, Sajithlal G, Hulla W, Schmid G, Herceg Z, Digweed M, Wang ZQ. (2003) Nbn heterozygosity renders mice susceptible to tumor formation and ionizing radiation-induced tumorigenesis. Cancer Res, 63, 7263-7269. [PubMed]
• Herceg Z, Hulla W, Gell D, Cuenin C, Lleonart M, Jackson S, Wang ZQ. (2001) Disruption of Trrap causes early embryonic lethality and defects in cell cycle progression. Nat Genet, 29, 206-211. [PubMed]