Alexander Bishop, D. Phil.

Associate Professor, Cell Systems and Anatomy, GCCRI

The interest of our lab is to identify and understand mechanisms of damage survival. People who inherit a deficiency in damage response are predisposed to develop cancer, usually as children or young adolescents. Further, most cancer treatments are based on damaging cancer cells, so understanding why a chemotherapy works, and for which patients, should lead to more effective and less toxic treatments that will increase the cure rate and improve quality of life for cancer survivors. 

My research focus for the last 20 years has been on DNA repair and DNA damage response. For this my lab uses a variety of model systems, including in vivo mouse models and tissue culture systems. DNA damage response and repair is central to normal development and when aberrant, developmental defects, aging phenotypes and cancer ensue. Our work reflects these various aspects of DNA damage response and DNA repair biology, often taking what might be termed a systems biology approach. In general, we apply the knowledge we gain to understand how these processes relate to cancer development and treatment. For example, we recently elucidated that the chemosensitivity observed for Ewing sarcoma is due to protein interactions of the fusion oncogene EWS-FLI1 interfering with the normal biology of EWSR1, resulting in BRCA1 being trapped in a transcription complex and unavailable to promote DNA repair. These findings are a paradigm shift in our understanding of a disease that has largely been studied to understand how the EWS-FLI1 gene expression program drives the etiology of this cancer. This work was published in Nature. We have also published papers delineating how the NRF2 pathway responds to alkylation damage to protect against unfolded protein response, again building on our systems biology approaches. I have a particular interest in the ATM/p53/BRCA1 and NRF2 damage response pathways and how they relate to control of DNA replication, homologous recombination and cancers. Towards this end, we have a tremendous set of resources to evaluate DNA repair and damage response and expertise in RNAi, CRISPR, gene expression, ChIP, protein interactions, bioinformatics, DNA combing, transcription stress and metabolomics available. 

Related diseases: Cancer, Ewing sarcoma, breast cancer, Ataxia telangiectasia, Bloom syndrome, Li-Fraumeni

Techniques: Cell biology, molecular genetics, RNAi, CRISPR, gene expression, ChIP, protein interactions, mouse genetics, cancer xenografts, bioinformatics, DNA combing, transcription assays as well as metabolic flux, oxygen flux assays and metabolomics