Associate Professor, Director of the Institute of Biochemistry
|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 post-transcriptional and translational regulation of gene expression. The appropriate regulation of gene expression is fundamental to life. Conversely, abnormal gene expression is associated with a variety of human diseases including cancers, developmental disorders and neurodegenerative diseases. We use a variety of molecular biology, cell biology, genetic and functional genomics approaches to decipher these responses using predominantly cell culture models.
- Post-transcriptional control of gene expression
A variety of physical and chemical agents lead to the activation of the p53 protein. The p53 protein is a transcription factor that regulates a large number of stress responsive mRNAs. We use p53 as a model transcriptional program to ask fundamental questions regarding post-transcriptional regulatory mechanisms. We have used oligonucleotide microarrays to study the p53 response on a genome wide scale and we found remarkable complexity. For example, the p53 protein regulates the expression RNA binding proteins and microRNAs that in turn affect the p53 response itself creating regulatory loops. Understanding how these mechanisms fine tune gene expression is an ongoing focus in the laboratory.
- Spliceosome inhibition as a post-transcriptional stress
Pre-mRNA splicing is required for mRNA synthesis to remove introns from primary transcripts. A massive RNA-protein complex, the spliceosome, catalyzes pre-mRNA splicing. A variety of small molecule inhibitors of the spliceosome have been identified that serve as important experimental tools, as they target spliceosome assembly at distinct stages and affect pre-mRNA splicing in different ways. We are interested in understanding how disruption of normal mRNA processing affects cell biology.
- Role of transcription-coupled repair in DNA damage responses
Many DNA damaging agents are cell lethal at high doses or concentrations. Sensitivity to these agents is multifactorial but may involve decreased DNA repair capacity and the activation of specific cell signaling pathways. 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. Conversely, disruption of the repair process impedes RNA synthesis and the production of mature mRNAs. We have found that this DNA repair pathway plays a critical role in determining the response of human cells to a variety of agents including ultraviolet light and cisplatin. Ongoing efforts are directed at understanding how unrepaired DNA lesions cause transcriptional stress and lead to cell death.
Exceptional students at all levels of study are encouraged to apply.
* Trainees in my laboratory
*Vanzyl, E.J., *Rick, K.R.C., *Blackmore, A.B., *MacFarlane, E.M. and McKay, B.C., 2018, Flow cytometric analysis of isoginkgetin treated cells identifies changes in S and M phases as novel cellular responses to spliceosome inhibition, PLoSONE, 13(1):e0191178
*Chmara, J., *Browning, J.W.L., Atkins, H. Sabloff, M. and McKay, B.C., 2018, Rapid decrease in KRT14 and TP53 mRNA expression in the buccal mucosa of patients receiving total body radiation for allogeneic stem cell transplantation, Radiat. Res., 189, 213-218.
Hassan, E.M., Willmore, W.G., McKay, B.C. and DeRosa, M.C., 2017, In vitro selections of mammaglobin A and mammaglobin B aptamers for the recognition of circulating breast tumor cells, Scientific Reports, 7, 14487, doi:10.1038/s41598-017-13751-z
*Cabrita M.A., *Bose, R., *Vanzyl, E.J., *Pastic, A., Hamill, J.D. *Pan, E., *Marcellus, K.A., and McKay, B.C., 2017, The p53 protein induces stable miRNAs that have the potential to modify subsequent p53 responses, Gene 608, 86-94
*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