Dr. Alexander Bishop's lab is aimed at understanding the
contribution of different genes to genomic instability and the role of
such instability in development, aging and carcinogenesis.
used include RNAi knockdown, transgenic over-expression and both
constitutive and conditional knock-out models in a variety of systems
including Drosophila tissue culture, mammalian tissue culture and mouse
The central question addressed in the laboratory is what is the
effect on genomic stability of modulating a gene particularly after
exposure to a carcinogenic agent. We assess genomic instability by
measuring homologous recombination (HR) or following the machinery
involved in this process.
HR repair is a significant component of the
cellular repair process in a replicating cell, and most importantly,
responds to the widest variety of DNA damages, from oxidative stress,
alkylation damage, bulky adducts on DNA as well as cross-links and
Brown AD, Sager BW, Gorthi A, Tonapi SS, Brown EJ, Bishop AJ. ATR Suppresses Endogenous DNA Damage and Allows Completion of Homologous Recombination Repair. PLoS One. 2014 Mar 27;9(3):e91222.
Lee IH, Kawai Y, Fergusson MM, Rovira II, Bishop AJ, Motoyama N, Cao L, Finkel T. Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress. Science. 2012 Apr 13;336(6078):225-8.
Brown AD, Claybon AB, Bishop AJ. A conditional mouse model for measuring the frequency of homologous recombination events in vivo in the absence of essential genes. Mol Cell Biol. 2011 Sep;31(17):3593-602.
Ravi D, Chen Y, Karia B, Brown A, Gu TT, Li J, Carey MS, Hennessy BT, Bishop AJ. 14-3-3 Ïƒ expression effects G2/M response to oxygen and correlates with ovarian cancer metastasis. PLoS One. 2011 Jan 10;6(1):e15864.
Ravi D, Wiles AM, Bhavani S, Ruan J, Leder P, Bishop AJ. A network of conserved damage survival pathways revealed by a genomic RNAi screen. PLoS Genet. 2009 Jun;5(6):e1000527.