|Degrees:||B.Sc. (Toronto), M.Sc. (Brock), Ph.D. (McMaster)|
|Phone:||613-520-2600 x 3265|
|Office:||249 Nesbitt Building|
|Website:||Visit my lab website|
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.
* Trainees in my laboratory
Cabrita M.A., Vanzyl, E.J., Hamill, J.D. Pan, E., Marcellus, K.A.,Tolls, V.J., Alonzi, R.C., Pastic, A., Rambo, T.M.E., Sayed, H. and McKay, B.C., 2016, A Temperature Sensitive Variant of p53 Drives p53-Dependent MicroRNA Expression without Evidence of Widespread Post-Transcriptional Gene Silencing, PLOS ONE, 11(2):e0148529.
Sriram, R., Lo, V., Pryce, B., Antonova, L., Mears, A.J., Daneshmand, M., McKay, B., Conway, S.J., Muller, W.J. and Sabourin, L.A. 2015, Loss of Periostin/OSF-2 in ErbB2/Neu-driven tumors results in androgen receptor-positive molecular apocrine-like tumors with reduced Notch1 activity, Breast Cancer Research, 17(1):7
Ruddy, S.C., Lau, R., *Cabrita, M.A., McGregor, C., McKay, B.C., Murphy, L.C., Wright, J.S., Durst, T. and Pratt, M.A.C. 2014, Preferential estrogen receptor β ligands reduce Bcl-2 expression in hormone-resistant breast cancer cells to increase autophagy, Mol. Cancer Ther.,13(7) 1882-1893.
McKay, B.C., 2014, Post-transcriptional control of DNA damage responsive gene expression, Antioxid Redox Signal. 20(4):640-54.
*Melanson, B.D., *Cabrita, M.A., *Bose, R., Hamill, J.D., * Pan, E., *Brochu, C., *Marcellus, K.A., Zhao, T.T., Holcik, M. and McKay, B.C., 2013, A novel cis-acting element from the 3’UTR of DNA damage-binding protein 2 mRNA links transcriptional and post-transcriptional regulation of gene expression, Nuc Acids Res, 41(11): 5692-703.
McKay, B.C. and Cabrita, M.A.*, 2013, Arresting transcription and sentencing the cell: the consequences of blocked transcription, Mech. Ageing Devel, 134 (2013) 243–252.
*Brochu, C., *Cabrita, M.A., *Melanson, B.D., Hamill, J.D., Huber, L., Pratt, C. and McKay, B.C., 2013, NF-κB-dependent role for cold-inducible RNA binding protein in regulating interleukin 1β, PLoS One, 8(2):e57426.
*Melanson, B.D., *Bose, R., Hamill, J.D., *Marcellus, K., *Pan E.F. and McKay, B.C., 2011, The role of mRNA decay in p53-induced gene expression, RNA, 17, 2222-2234.
*Stubbert, L.J., *Smith, J.M. and McKay, B.C., 2010, Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin, BMC Cancer, 10, 207
McKay, B.C., *Stubbert, L.J. *Fowler, C.C. *Smith, J.M., *Cardamore, R.A. and *Spronck, J.C., 2004, Regulation of ultraviolet light-induced gene expression by gene size, Proc Natl Acad Sci USA, 101, 17, 6582-6586.
For a more complete list see: McKay, BC