• 1987, National Arthritis Foundation Postdoctoral Fellowship
  
• 1987-1990, National Research Service Award, NIAMS, NIH
  
• 1991-1994, National Arthritis Foundation Investigator Award
  
• 1993, AIMM (Advances in Mineral Metabolism) Young Investigator Award
  
• 1994-1999, MRC (Medical Research Council of Canada) Scholar Award
  
• 1995, University Research Award (University of Calgary)
  
• 1996, Research Excellence Envelope Award (Province of Alberta)
  
• 1999-2004, AHFMR (Alberta Heritage Foundation for Medical Research) Senior Scholar Award
  

Normal skeletal growth requires exquisite control of endochondral growth plate development and progression in order to achieve proper bone and marrow formation. Disruptions in several genes such as those for the PTHrP receptor, FGFR3 receptor, TGF-beta receptor type II, vitamin D receptor, and thyroid hormone receptor result in disorganization of the growth plate and abnormal endochondral ossification (i.e. the transition from cartilage to bone) in mice. Multiple human genetic skeletal disorders result from the perturbation of the balance between proliferation and maturation of chondrocytes within the growth plate. These include chondrodysplasias, overgrowth diseases such as Beckwith-Wiedemann syndrome, dwarfisms, and neoplasms affecting cartilage and bone. Environmental interferences, for example fetal exposure to smoking resulting in diminished and disproportionate skeletal growth, or trauma to bones prior to growth plate closure, also affect the integrity of mature bone. Our laboratory uses several knock-out and transgenic lines of mice to study the mechanisms that result in balanced proliferation and maturation of growth plate chondrocytes.

My research focuses on the goals of understanding the mechanisms We are using mice deficient in the transcription factor ATF-2 as a model to study growth plate chondrocyte proliferation control. This mouse is dwarfed (approximately half the size of a normal mouse) and displays significant reductions in growth plate size.We have hypothesized that ATF-2, a transcription factor, is a major player in the control of growth plate chondrocyte proliferation, and have determined that it directly targets and activates several genes that control cell cycle progression. These genes include those for cyclin D1, cyclin A, the retinoblastoma protein (pRb), and related pocket proteins p107 and p130. c-Fos and Bcl-2 also require ATF-2 for expression. We are currently determining the signaling pathways that stimulate ATF-2, and the mechanisms by which the target proteins control proliferation.

Cell cycle exit is the initial stage of chondrocyte maturation in growth plate chondrocytes. We have shown that the MAP Kinase pathway stimulates p21^CIP/WAF1 expression (a marker for cell cycle exit) in chondrocytes. FGFR3 and its ligands FGF9 and FGF18 are involved in the signaling pathways that promote maturation. We are using the FGFR3 knock-out mouse, which has an overgrowth phenotype, and the Achondroplasia mouse, which contains the same mutation in amino acid 380 that causes the human Achondroplasia dwarfism, to examine the cellular and biochemical machinery that controls both normal and premature cell cycle exit, resulting in reduction in skeletal growth.

• Control of skeletal growth by ATF-2
  
• Mediation of chondrocyte maturation by the Raf signaling pathway
  
• Effects of hypoxia fetal skeletal development and growth
  

1. F. Beier, R. J. Lee, A. C. Taylor, R. G. Pestell, and P. LuValle, 1999. Identification of the cyclin D1 gene as a target of ATF-2 in chondrocytes, Proc. Natl. Acad. Sci. 96: 1433-1438.
   
2. F. Beier, A. Taylor, and P. LuValle, 1999. The Raf-1/MEK/ERK pathway regulates the expression of the p21Cip/Waf1 gene in chondrocytes. J. Biol. Chem: 274: 30273-30279.
   
3. Z. Ali, F. Beier, T. Leask, and P. LuValle, 1999, Skeletal development and regeneration, Current Opin. Orthopedics 10 (6): 466-471.
   
4. F. Beier, A. Taylor, P. LuValle, 2000. Activating transcription factor 2 is necessary for maximum activity and serum induction of the cyclin A promoter in chondrocytes, J. Biol. Chem. 275:12948-12953.
   
5. P. LuValle and F. Beier, 2000. Cell cycle control in growth plate chondrocytes, Frontiers in Biosciences 5: d493-503.
   
6. F. Beier, Z. Ali, D. Mok, A. C. Taylor, T. Leask, C. Albanese, R. G. Pestell, and P. LuValle, 2001. TGFb and PTHrP control chondrocyte proliferation by activating cyclin D1 expression, Molec. Biol. of the Cell 12: 3852-3863.
   
7. F. Beier and P. LuValle, 2002. The cyclin D1 and cyclin A genes are targets of activated PTH/PTHrP receptors in Jansen’s metaphyseal chondrodysplasia, Mol. Endocrinol. 22:565-572.
   
8. P. LuValle, Q. Ma, and F. Beier, 2003. The role of ATF-2 in skeletal growth control, Journal of Bone and Joint Surgery 85-Asuppl 2:133-6.