Alexandre Blais

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Alexandre Blais
Associate Professor, Department of Biochemistry, Microbiology and Immunology

Work: (613) 562-5800 ext. 8463
email: alexandre.blais@uottawa.ca

Picture of Dr. Alexandre Blais

Biography

Our lab studies gene regulatory proteins called transcription factors and the critical role that they play in the formation and healing of skeletal muscle. We are interested in understanding, at the molecular level, the mode of action of these proteins and how they might cooperate together to control this important health-related process. We address this question by combining the power of genomics with bioinformatic methods.

The Blais lab accepts students from graduate programs in Biochemistry and Human Molecular Genetics.

A microscopic image of a regenerating mouse muscle

Immunofluorescence detection of myogenic transcription factors in the regenerating tibialis anterior muscle of a mouse

Research Program

Our lab studies how certain proteins, called transcription factors, govern the fate of cells. In particular, transcription factors determine which genes are going to be expressed in a given cell but not another, so they can have a profound impact on the identity and function of all cells of the human body. Our research group aims to determine the mode of action of transcription factors involved in skeletal muscle development and regeneration and the control of cell proliferation.

In our study of myogenesis, we have found that two transcription factors called Six1 and Six4 participate in controlling the ability of muscle precursor cells to differentiate into mature muscle fibers. Using ChIP-seq technology, we have determined the identity of the genes regulated by Six1 and Six4 and have started to elucidate the mode of action of these two proteins. We have found that they often target genes that are also regulated by the MyoD transcription factor, which is important because MyoD is seen as the master regulator of skeletal muscle formation. We are now investigating how Six1, Six4 and MyoD cooperate by looking at the structure of DNA and chromatin at their common target genes.

The cell division cycle is a very fundamental process that allows cellular proliferation, tissue growth and homeostasis. Transcription factors are needed to control cell division in a very tight manner, because unbridled proliferation can lead to cancer. We are using functional genomics techniques to understand how this precise regulation of the cell cycle is made possible and what the consequences of deregulation can be.

Selected Publications

Nandi S, Blais A, Ioshikhes I. Identification of cis-regulatory modules in promoters of human genes exploiting mutual positioning of transcription factors. Nucleic Acids Res. 2013 Oct;41(19):8822-41. doi: 10.1093/nar/gkt578. Epub 2013 Aug 2.

Liu Y, Chakroun I, Yang D, Horner E, Liang J, Aziz A, Chu A, De Repentigny Y, Dilworth FJ, Kothary R, Blais A. Six1 regulates MyoD expression in adult muscle progenitor cells. PLoS One. 2013 Jun 28;8(6):e67762. doi:10.1371/journal.pone.0067762. Print 2013.

Julian LM, Vandenbosch R, Pakenham CA, Andrusiak MG, Nguyen AP, McClellan KA, Svoboda DS, Lagace DC, Park DS, Leone G, Blais A, Slack RS. Opposing regulation of Sox2 by cell-cycle effectors E2f3a and E2f3b in neural stem cells. Cell Stem Cell. 2013 Apr 4;12(4):440-52. doi: 10.1016/j.stem.2013.02.001. Epub 2013 Mar 14.

Liu Y, Nandi S, Martel A, Antoun A, Ioshikhes I, Blais A. Discovery, optimization and validation of an optimal DNA-binding sequence for the Six1 homeodomain transcription factor. Nucleic Acids Res. 2012 Sep 1;40(17):8227-39. Epub 2012 Jun 22.

Ghanem N, Andrusiak MG, Svoboda D, Al Lafi SM, Julian LM, McClellan KA, De Repentigny Y, Kothary R, Ekker M, Blais A, Park DS, Slack RS. The Rb/E2F pathway modulates neurogenesis through direct regulation of the Dlx1/Dlx2 bigene cluster. J Neurosci. 2012 Jun 13;32(24):8219-30. doi: 10.1523/JNEUROSCI.1344-12.2012.

Ryan T, Liu J, Chu A, Wang L, Blais A, Skerjanc IS. Retinoic acid enhances skeletal myogenesis in human embryonic stem cells by expanding the premyogenic progenitor population. Stem Cell Rev. 2012 Jun;8(2):482-93. doi:10.1007/s12015-011-9284-0.

Liu Y, Chu A, Chakroun I, Islam U, Blais A. Cooperation between myogenic regulatory factors and SIX family transcription factors is important for myoblast differentiation. Nucleic Acids Res. 2010 Nov;38(20):6857-71. doi:10.1093/nar/gkq585. Epub 2010 Jul 2.

Seenundun S, Rampalli S, Liu QC, Aziz A, Palii C, Hong S, Blais A, Brand M, Ge K, Dilworth FJ. UTX mediates demethylation of H3K27me3 at muscle-specific genes during myogenesis. EMBO J. 2010 Apr 21;29(8):1401-11. doi: 10.1038/emboj.2010.37. Epub 2010 Mar 18.

Niro C, Demignon J, Vincent S, Liu Y, Giordani J, Sgarioto N, Favier M, Guillet-Deniau I, Blais A, Maire P. Six1 and Six4 gene expression is necessary to activate the fast-type muscle gene program in the mouse primary myotome. Dev Biol. 2010 Feb 15;338(2):168-82. doi: 10.1016/j.ydbio.2009.11.031. Epub 2009 Dec 4.

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