Priority Research Areas: Genomics

Many human maladies have an underlying genetic basis. The Genomics groups, led by Dr. Robert Hancock, will utilize advanced functional genomics and bioinformatics to investigate the relationship between the phenotype of the disease and the underlying genetic mutations. Our focus is on diseases that dysregulate inflammation, with or without the involvement of chronic infections, including Cystic Fibrosis, Chronic Granulomatous Disease, and a variety of genetic mutations in key genes involved in immune signaling, including IRAK4 deficiency.

The objective is to utilize Systems Biology methods to determine key regulatory steps that explain dysfunctional inflammation/innate immunity and to use this knowledge to devise novel treatments and markers of disease. The group is also interested in polygenic diseases that impact on susceptibility to infection and/or dysregulate inflammation, including sepsis, inflammatory bowel disease and tuberculosis.

References
Davidson, D.J., A.J. Currie, DM.E. Bowdish, K.L. Brown, C.M. Rosenberger, RC. Ma, J. Bylund, P.A. Campsall, A. Puel, C. Picard, J.-L. Casanova, S.E. Turvey, R.E.W. Hancock, R.S. Devon, and D.P. Speert. 2006. IRAK-4 mutation (Q293X): rapid detection, and characterisation of defective posttranscriptional TLR/IL-1R responses in human myeloid and non-myeloid cells. J. Immunol. 177:8202-11.

Bylund, J., K.L. MacDonald, K.L. Brown, P. Mydel, L.V. Collins, R.E.W. Hancock and D.P. Speert. 2007. Enhanced inflammatory responses of chronic granulomatous disease leukocytes involve reactive oxygen species-independent activation of NF-kB. Europ. J. Immunol. 37:1087-1096.

Brown, K.L., J. Bylund, K.L. MacDonald, G.X. Song-Zhao, M.R. Elliott, R. Falsafi, R.E.W. Hancock and D.P. Speert. 2008. ROS-deficient monocytes have aberrant gene expression that correlate with inflammatory disorders of chronic granulomatous disease. Clin Immunol. 129:90-102.

Lynn, D.J., G.L. Winsor, C. Chan, N. Richard, M.R. Laird, A. Barsky, J.L. Gardy, F.M. Roche, T.H.W. Chan, N. Shah, R. Lo, M. Naseer, J. Que, M. Yau, M. Acab, D. Tulpan, M. Whiteside, A. Chikatamarla, B. Mah, T.M. Munzner, K. Hokamp, R.E.W. Hancock, and F.S.L. Brinkman. 2008. Facilitating systems level analyses of the mammalian innate immune response. Molec. Systems Biol. 4:218. Epub.

Blohmke, C.J., A.F. Hirschfeld, I. Elias, R.E. Victor, D.G. Hancock, A.G.F. Davidson, P.G. Wilcox, K.D. Smith, J. Overhage, R.E.W. Hancock, and S.E. Turvey. 2008. Innate immunity mediated by TLR5 as a novel anti-inflammatory target for cystic fibrosis lung disease. J. Immunol. 180:7764-7773.

Hamill, P., K. Brown, H. Jenssen and R.E.W. Hancock. 2009. Novel anti-infectives: is host defence the answer? Curr. Opin. Biotechnol. 19:628-636.