Bruce Mckay

Biography

Bruce McKay Associate Professor Degrees: B.Sc. (Toronto), M.Sc. (Brock), Ph.D. (McMaster)

Research Interest

My primary research interests lie in the area of genomic instability in cancer and cancer therapy.  Cancer is a disease of genomic instability and many tumour suppressor proteins including the p53 tumour suppressor protein, retinoblastoma protein and breast cancer susceptibility protein play critical roles in DNA damage responses.  We use a variety of molecular biology, cell biology and functional genomics approaches to decipher these responses using predominantly cell culture models.  We also have some clinical collaborations to extent our expertise to the analysis of patient samples.  Efforts in the lab are currently directed in a variety projects. Role of transcription-coupled repair in cancer therapy Many conventional cancer therapies are DNA damaging agents.  Following initial positive responses, tumours may develop that are resistant to the initial therapy.  Resistance is multifactorial but it can involve increased DNA repair capacity.  Transcription-coupled repair is a specific DNA repair pathway that couples transcription to the repair of transcription-blocking DNA lesions, permitting transcription in the face of DNA damage.  We have found that this DNA repair pathway plays a critical role in determining the response of tumour cells to cisplatin, one of the most commonly used chemotherapeutic agents.  Ongoing efforts are directed at understanding how unrepaired lesions lead to cell death and whether strategies to target this DNA repair pathway may be of clinical benefit. Post-transcriptional and translational regulation of gene expression DNA damage leads to the activation of a variety of signaling cascades.  These can lead to widespread changes in gene expression.   Many of the most prominent changes in gene expression result from the activation of transcription factors like the p53 tumour suppressor.  We have used oligonucleotide microarrays to study the p53 response on a genome wide scale and we found remarkable complexity in the p53 response.  For example, p53 regulates the expression of RNA binding proteins and microRNAs that in turn regulate gene expression through post-transcriptional and translational mechanisms.  Understanding the contribution of these many levels of regulation to cancer and cancer therapy is an ongoing focus in the laboratory. Through collaborations with physicians at the Ottawa Hospital, we are analyzing changes in miRNA and mRNA expression in samples obtained from patients during the course of their treatments. The role of splicing in cancer therapy Recent evidence suggests that tumour cells exhibit distinct patterns of pre-mRNA splicing and that tumour cells may be sensitive to agents that target components of the spliceosome (the complex that is responsible for pre-mRNA splicing).  We are looking at the effects of a naturally occurring splicing inhibitor (isoginkgetin) on tumour cell responses at the cellular and genomic level. Exceptional students at all levels of study are encouraged to apply.