Associate Research Scientist, Hospital for Special Surgery
Director, Osteolysis Research Laboratory, Hospital for Special Surgery
Purdue, P.E. and P.B. Lazarow. Peroxisome Biogenesis. Annual Review of Cell and Developmental Biology 17: 701-752 (2001).
Purdue, P.E. And P.B. Lazarow. Pex18p is constitutively degraded during peroxisome biogenesis. J. Biol. Chem. 276: 47684-47689 (2001).
Purdue, P.E., J. Zhang, M. Skoneczny and P.B. Lazarow. Rhizomelic chondrodysplasia punctata is caused by deficiency of human Pex7p, a homologue of the yeast PTS2 receptor. Nature Genetics, 15: 381-384 (1997).
Danpure, C.J. and P.E. Purdue. Primary hyperoxaluria. In “The Metabolic and Molecular Bases of Inherited Disease” (7th Edition), McGraw-Hill, Eds. Scriver, C.R., Beaudet, A.L., Sly, W.S. and Valle, D., pp 2385-2424 (1995)
DS Rakshit, K Ly, TK Sengupta, BJ Nestor, TP Sculco, LB Ivashkiv and E Purdue. (2005) Wear debris inhibition of anti-osteoclastogenic signaling by IL6 and IFN-gamma; mechanistic insights and implications for periprosthetic osteolysis. Submitted to The Journal of Bone and Joint Surgery.
Nair DM, Purdue PE, Lazarow PB. (2004) Pex7p translocates in and out of peroxisomes in Saccharomyces cerevisiae. J. Cell Biol. 167:599-604.For more publications, please see the PubMed listing.
Of the more than 168,000 patients who undergo hip replacement surgery every year in the U.S., as many as 20% require subsequent revision surgery due to aseptic loosening and periprosthetic osteolysis. The goal of the Osteolysis Research Laboratory is to develop, at the cellular and molecular levels, a better understanding of the events which lead to periprosthetic osteolysis. We are approaching this in four ways:
1. Firstly, we will be focusing on the roles of wear debris particles derived from the prostheses or bone cement in perturbing the complex intracellular signaling pathways within the cells around the prosthesis. It is known that macrophages within the periprosthetic membrane phagocytose these particles, and results from our laboratory have shown that this interaction between macrophage cells and particles can initiate pro-inflammatory cytokine signaling pathways, whilst concurrently inhibiting anti-inflammatory pathways.
2. In a second, related, project we are addressing the initial interaction of wear debris particles with receptors on the external surface of macrophages and other cells within the periprosthetic space. Our preliminary evidence is that different wear debris particles are recognized by different phagocytosis receptors on macrophages. Furthermore, opsonization patterns vary between particles of different compositions, and this will influence cell surface interactions.
3. We will complement our cell culture studies by directly examining revision tissues obtained from patients. Systematic analysis of these tissues by immunohistochemistry and in-situ hybridization is expected to provide important indicators of the mechanism of pathogenesis.
4. Finally, we are developing a mouse model for periprosthetic osteolysis. Currently used mouse models of osteolysis do not involve prostheses and do not target the effective joint space. The model under development at HSS involves introduction of bone cement particles around a titanium pin inserted into the tibia and, as such, is more closely analogous than other models to the human disease. Once optimized, we will use this model to test the involvement of key cytokines and other signaling molecules in wear debris induced osteolysis