David Picketts, PhD dpicketts@ohri.ca (613) 737-8989 (T) (613) 737-8803 (F) General Campus (see Contact page for maps)

Senior Scientist, Regenerative Medicine, Ottawa Hospital Research Institute

Associate Professor, Department of Biochemistry, Microbiology, and Immunology, Faculty of Medicine,University of Ottawa

Biographical Sketch.

Dr. Picketts completed a PhD at Queen's University (Kingston) with Dr. David Lillicrap studying the transcriptional regulation of the Factor IX gene. He then pursued postdoctoral research in Oxford, England with Dr. Douglas Higgs at the Institute of Molecular Medicine. Here he began studies with another research fellow, Dr. Richard Gibbons to identify the gene responsible for the ATR-X syndrome, a severe form of X-linked mental retardation. They identified the gene in 1995, establishing the paradigm that dysfunctional chromatin remodelling proteins can cause human disease, specifically XLMR. Dr. Picketts remains an avid ice hockey enthusiast playing or coaching several times a week and he is an Oxford Ice Hockey Team alumni.

Research Interests

• Human genetic disease arising from defects in epigenetic gene regulation.

Major Research Activities

Chromatin remodeling proteins and XLMR
Chromatin remodeling proteins play a dynamic role in the regulation of gene expression through the alteration of nucleosome structure (histone acetylation, phosphorylation and methylation) or the ATP dependent repositioning of nucleosomes (SWI/SNF complex, ISWI). Their involvement in genetic disease was established by our cloning of the ATRX gene, a novel SWI/SNF family member that is mutated in a severe X-linked mental retardation syndrome usually associated with a thalassemia. This paradigm was extended by the identification of mutations in MECP2 and CBP in Rett syndrome and Rubinstein-Taybi syndrome, respectively. We are utilizing a multifaceted approach to define the proteins that interact with ATRX and determine the mechanism(s) underlying the neural defects associated with these XLMR patients. As part of this effort we are developing mouse models.

Moreover, to extend our analysis of the role of chromatin remodeling proteins in neural development we have characterized the human and murine SNF2H and SNF2L genes (homologues of the Drosophila ISWI gene), the latter as an XLMR candidate gene within Xq25-26. We observed that SNF2H is expressed in proliferating neuronal cell populations whereas SNF2L is expressed predominantly in differentiating and/or maturing neurons. Studies are underway to characterize the role of these proteins in neural development.

Selected Publications

Bérubé, NG, Jagla M, Vanderluit, JL, Garrick, D, Gibbons, RJ, Higgs, DR, Slack, RS, and Picketts, DJ. The chromatin remodeling protein ATRX is critical for neuronal survival during corticogenesis. (2005) J. Clin. Invest. 115: 258-267. PMID: 544602

Lazzaro, MA, Pepin, D, Pescador, N, Murphy, BD, Vanderhyden, BC, and DJ Picketts. The ISWI protein SNF2L regulates steriodogenic acute regulatory protein (StAR) expression during terminal differentiation of ovarian granulose cells. (2006) Mol. Endocrinol. 20: 2406-2417. PMID: 16740656

Yip, DJ and Picketts, D.J. Increasing D4Z4 repeat copy number compromises C2C12 myoblast differentiation. (2003) FEBS Lett. 537, 133-138 PMID: 12606045