René St-Arnaud, Ph.D.

Faculty Profiles

 RStA

Contact Information:

Genetics Unit
Shriners Hospital for Children
1529 Cedar Avenue
Montreal (Quebec) H3G 1A6
Tel: 514-282-7155
Fax: 514-842-5964
E-mail: rst-arnaud@shriners.mcgill.ca

 

 

Biosketch:

Dr. St-Arnaud is a Senior Investigator at the Canadian Shriners Hospital for Children, and a Professor of Medicine, Surgery, and Human Genetics at McGill University. His research interests include the control of gene expression in bone cells, and vitamin D metabolism. He has made major contributions to these fields, including the cloning of key vitamin D metabolic enzymes, the cloning and characterization of novel transcriptional regulators controlling bone mass accrual, and the engineering of useful animal models of metabolic bone disease. He was awarded the Fuller Albright Award of the American Society for Bone and Mineral Research (ASBMR), the Outstanding Investigator in the Bone Field Award from the International Bone and Calcium Institute, and the Excellence Prize of the Foundation for Research into Pediatric Diseases. He chaired the 2005 Gordon Research Conference on Bones & Teeth and was elected to the Board of Directors of the Advances in Mineral Metabolism meeting. He is a current Council member for the ASBMR.

 

Summary of current research:

a) Vitamin D synthesis in bone: molecular genetic analysis

The enzyme 25-hydroxyvitamin D-1α-hydroxylase (1α-OHase) converts 25(OH)D to 1,25(OH)2D, the active form of vitamin D. We have engineered mutant strains of mice that do not express the 1α-OHase gene in chondrocytes. In parallel, we plan to engineer strains of mice overexpressing a 1α-OHase transgene in chondrocytes. Contrasting the phenotype of the transgenic animals to that of the knock-out animals should help elucidate the role of local production of the hormonal form of vitamin D during cartilage formation, maturation, and growth. The 25-hydroxyvitamin D-24-hydroxylase enzyme (24-OHase) converts 25(OH)D to 24,25(OH)2D, a metabolite that may be important during fracture repair. We have engineered a strain of mice deficient for the 24-OHase enzyme. Fracture repair will be analyzed in the 24-OHase-deficient mice using the distraction osteogenesis mouse model. These studies will address key aspects of vitamin D biology and lead to the development of new animal models of disease involving the vitamin D endocrine system.

b) Gene expression in bone cells

We have cloned the transcriptional coactivator, αNAC, that is expressed in bone during development. We have shown that the Integrin Linked Kinase (ILK) can efficiently phosphorylate αNAC. We have identified a novel factor interacting with αNAC that we termed FIAT, for Factor Inhibiting ATF4-mediated Transcription. Our results show that FIAT inhibits ATF4 activity and osteocalcin gene transcription. We are currently generating strains of mice deficient for αNAC, FIAT, and ILK. Our recent results show that chondrocyte-specific ablation of ILK leads to chondrodysplasia while its inactivation in osteoclasts leads to mild osteopetrosis. FIAT overexpression in osteoblasts reduces bone mass in vivo. Our research will further our knowledge of the molecular mechanisms regulating bone cell-specific gene expression and allow to develop animal models of bone diseases involving the genes that we have cloned.

 

Selected key publications:

  • St-Arnaud, R., S. Messerlian, J.M. Moir, J.L. Omdahl, and F.H. Glorieux. 1997. The 25-hydroxyvitamin D 1-alpha-hydroxylase gene maps to the pseudovitamin D-deficiency rickets (PDDR) disease locus. J. Bone Miner. Res. 12: 1552-1559.
  • Dardenne, O., J. Prud’homme, A. Arabian, F.H. Glorieux, and R. St-Arnaud. 2001. Targeted inactivation of the 25-hydroxyvitamin D3-1α-hydroxylase gene (CYP27B1) creates an animal model of pseudo vitamin D deficiency rickets, Endocrinology 142: 3135-3141.
  • Terpstra, L., J. Prud’homme, A. Arabian, S. Takeda, G. Karsenty, S. Dedhar, and R. St-Arnaud. 2003. Reduced chondrocyte proliferation and chondrodysplasia in mice lacking the Integrin-Linked Kinase (ILK) in chondrocytes. J. Cell Biol. 162: 139-148.
  • Akhouayri, O., I. Quélo, and R. St-Arnaud. 2005. Sequence-specific DNA binding by the αNAC coactivator is required for potentiation of c-Jun-dependent transcription of the osteocalcin gene. Mol. Cell. Biol. 25: 3452-3460.
  • Yu, V.W.C., G. Ambartsoumian, L. Verlinden, J.M. Moir, J. Prud’homme, C. Gauthier, P.J. Roughley, and R. St-Arnaud. 2005. FIAT represses ATF4-mediated transcription to regulate bone mass in transgenic mice. J. Cell Biol. 169: 591-601.
  • Akhouayri, O., and R. St-Arnaud. 2007. Differential mechanisms of transcriptional regulation of the mouse osteocalcin gene by Jun family members. Calcif Tissue Int 80: 123-131.
  • St-Arnaud, R. and B. ElChaarani. 2007. Identification of additional dimerization partners of FIAT, the Factor Inhibiting ATF4-mediated Transcription. Ann. NY Acad. Sci., in press.

 

Student supervision:

Number of M.Sc. students currently in the lab: 5

Number of Ph.D. students currently in the lab: 1

Number of Post-doctoral trainees currently in the lab: 3

 

New students opportunities:

Always looking for motivated, talented students interested in molecular genetics

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