• Scientist, Molecular Medicine Program, Ottawa Health Research Institute
• Assistant Professor, University of Ottawa, Department of Medicine, Division of Hematology
• Canada Research Chair in the Regulation of Gene Expression
• Associate Member of the Ottawa Institute for Systems Biology

Training

Postdoctoral Fellow Fred Hutchinson Cancer Research Center (Seattle, USA)
PhD Institut de Genetique et de Biologie Moleculaire et Cellulaire (Strasbourg, France)

Research Interests

Understanding the regulation of gene expression during hematopoiesis, and how this process is deregulated in leukemia.

Keywords

Chromatin, Transcription, Epigenetics, Quantitative Mass Spectrometry, β-globin locus, Leukemia, Hematopoiesis

Research Activities

Hematopoietic Stem cells have the capacity to differentiate along multiple lineages potentially giving rise to all cells present in the blood. This process is controlled by cell-specific and ubiquitously expressed transcription factors and cofactors. Defects in the transcriptional regulatory network of these cells can lead to leukemia. The major goal of our lab at the Sprott Centre for Stem Cell Research is to decipher the molecular mechanism of Hematopoietic Stem Cell differentiation towards the Erythroid Lineage (i.e. giving rise to red blood cells) and to understand how deregulation of this process can cause Leukemia. Towards this goal, we are using a systems biology approach including quantitative proteomics (isotope tagged methods), genomics (expression microarray, ChIP-sequencing), bioinformatics as well as molecular and cellular biology to understand the regulation of gene expression at the level of transcription, epigenetics and chromatin structure.

Major Awards

• Career Award, Canadian Research Chair (Tier 2) in Gene Expression, 2004 - 2009
• Career Development Award, Human Frontier Science Program Organization, 2005 -2007
• Postdoctoral Fellowship, Human Frontier Science Program, 2001-2004
• Postdoctoral Fellowship, European Molecular Biology Organization, 2001

Active Research Funding

• National Cancer Institute of Canada, Operating Grant 2005 – 2008
• Human Frontier Science Program Organization, Career Development Award 2005 – 2007
• Canada Research Chair in Gene Expression, 2004 – 2009

Publications

1. C-P. Chaturvedi*, A.M. Hosey*, C. Palii, C. Perez-Iratxeta, Y. Nakatani, J.A. Ranish, F.J. Dilworth & M. Brand. Dual role for the methyltransferase G9a in the maintenance of ?-globin gene transcription in adult erythroid cells. Proceedings of the National Academy of Sciences USA, 10.1073/pnas.0906769106, 2009 * co-authors
    
2. A.M. Hosey & M. Brand. Chromatin-mediated spreading on active genes. Nature Structural and Molecular Biology 16 (1): 11-13, 2009
    
3. M. Brand, S. Rampalli, C-P. Chaturvedi, and F.J. Dilworth. Analysis of epigenetic modifications of chromatin at specific gene loci by native chromatin immunoprecipitation (N-ChIP) of nucleosomes isolated using hydroxyapatite chromatography. Nature Protocols 3 (3): 398-409, 2008
    
4. S. Rampalli, L. Li, E. Mak, K. Ge, M. Brand, S.J. Tapscott, and F.J. Dilworth. p38 MAPK signaling pathway regulates recruitment of Ash2L-containing methyltransferase complexes to specific genes during differentiation. Nature Structural and Molecular Biology 14: 1150-1156, 2007
    
5. C. Demers, C.P. Chaturvedi, J. A. Ranish, G. Juban, P. Lai, F. Morle, R. Aebersold, F. Dilworth, M. Groudine & M. Brand. Activator-mediated Recruitment of the MLL2 Methyltransferase Complex to the ?-globin Locus. Molecular Cell, 27: 573-584, 2007
    
6. J.A Ranish, M. Brand and R. Aebersold. Using stable isotope tagging and MS to characterize protein complexes and to detect changes in their composition. Methods in Molecular Biology, 359:17-35, 2007
    
7. J. Sun, M. Brand , Y. Zenke, S. Tashiro, M. Groudine and K. Igarashi. Heme regulates dynamics of Bach1 and NF-E2-related factors in the Maf transcription factor network. Proceedings of the National Academy of Sciences , 101 (6): 1461-1466, 2004
    
8. M. Brand , J. A. Ranish, N. T. Kummer, J. Hamilton, K. Igarashi, C. Francastel, T. Chi, G. R. Crabtree, R. Aebersold and M. Groudine. Dynamic changes in transcription factors complexes during erythroid differentiation revealed by quantitative proteomics. Nature Structural and Molecular Biology , 11 (1): 73-80, 2004
    
9. N. Cavusoglu , M. Brand , L. Tora and A. Van Dorsselaer. Novel subunits of the TATA Binding Protein Free TAF II -containing transcription complex identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry following one dimensional gel electrophoresis. Proteomics , 3 (2): 217-223, 2003
    
10. S. Hardy, M. Brand , G. Mittler, J. Yanagisawa, S. Kato, M. Meisterernst and L. Tora. TATA-binding protein-Free TAF-containing complex (TFTC) and p300 are both required for efficient transcriptional activation . Journal of Biological Chemistry 277: 32875-32882, 2002, S. Hardy and M. Brand are considered as equal first authors.
     
11. Y. G. Gangloff, J. C. Pointud, S. Thuault, L. Carre, C. Romier, S. Muratoglu, M. Brand , L. Tora, J. L. Couderc and I. Davidson. The TFIID components human TAF(II)140 and Drosophila BIP2 (TAF(II)155) are novel metazoan homologues of yeast TAF(II)47 containing a histone fold and a PHD finger. Molecular and Cellular Biology 21 (15): 5109-51021, 2001
     
12. M. Brand , J. G. Moggs, M. Oulad-Abdelghani, F. Lejeune, F. J. Dilworth, J. Stevenin, G. Almouzni and L. Tora. UV-damaged DNA binding protein in the TFTC complex links DNA damage recognition to nucleosome acetylation. The EMBO Journal 20 (12): 3187-3196, 2001
     
13. L. Tora, M. Brand , E. Wieczorek and D. Metzger. The role of TAF II 30-containing complexes in vertebrate gene regulation. in: Human Frontier Workshop VII on "Transcription Regulation in Eukaryotes" Eds. P. Chambon, R.D. Kornberg, T. Fukasawa and C. Coath. HFSP, Strasbourg, France. pp. 162-170, 1999
     
14. M. Brand , C. Leurent, V. Mallouh, L. Tora and P. Schultz. Three dimensional structures of the TAF II -containing complexes TFIID and TFTC. Science 286: 2151-2153, 1999 , M. Brand and C. Leurent are considered as equal first authors.
     
15. M. Brand , K. Yamamoto, A. Staub and L.Tora. Identification of TFTC subunits suggests a role in nucleosome acetylation and signal transduction. Journal of Biological Chemistry 274 (26): 18285-18289, 1999
     
16. E. Wieczorek, M. Brand , X. Jacq and L. Tora. Function of TAFII-containing complex without TBP in transcription by RNA polymerase II. Nature 393: 187-191, 1998 , E. Wieczorek and M. Brand are considered as equal first authors.

Current Lab Members

Chandra-Prakash Chaturvedi, PhD (postdoctoral fellow)
CIHR postdoctoral fellow
Alison Hosey, (postdoctoral fellow)
Canadian Cancer Society-Terry Fox Foundation postdoctoral fellow
Carmen Palii, PhD (postdoctoral fellow)
Computational Regulomics Training Program postdoctoral fellow
Cathy Zhang (graduate student)
Jianguo Wu, MSc (research technician)

Former Trainees

Zeshawn Awan (Master student 2005-2007)
Currently a scientific assessment officer at Health Canada