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Oregon Health & Science Univ
Molecular & Medical Genetics
Mail Code: L103
3181 SW Sam Jackson
Park Road
Portland, OR 97239
503-494-7703
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William A. Horton, M.D. - Professor
Oregon Health & Science University
3181 SW Sam Jackson Park Road
Mail Code SHC-RES
Portland, OR 97239
Office: 503-221-1537
Fax: 503-221-3451
E-Mail: wah@shcc.org
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 Most forms of dwarfism in humans result from genetic disturbances that play out in the growth plates of the developing skeleton. These disturbances adversely affect differentiating chondrocytes that normally synthesize and subsequently turnover cartilage template for bone growth. Local regulatory circuits act on different aspects of chondrocyte differentiation, such as proliferation, terminal differentiation, and apoptosis, to control bone growth. Elucidating how these circuits work and relate to one another will provide a means to understand the pathogenesis of the human disorders, such as achondroplasia, and a rational basis for developing effective new therapies. Our major focus is understanding how signals generated from FGF:FGF receptor interactions influence the cellular and molecular events of bone growth: how do they affect chondrocyte differentiation? how do they interact with signals from BMPs, PTHrP, Hedgehogs, other local growth factors? how do receptor mutations cause skeletal diseases? and how might defective signaling pathways be corrected therapeutically? A wide range of conventional cell and molecular biology and gene targeting techniques are employed as are novel strategies, such as live cell confocal microscopy, GFP lineage tracing and gene expression profiling, to analyze cell culture and mouse experimental models. |
SELECT PUBLICATIONS Hoffman LM, Garcha K, Karamboulas K, Cowan MF, Drysdale LM, Horton WA, Underhill TM (2006). BMP action in skeletogenesis involves attenuation of retinoid signaling. J Cell Biol 174:101-13 Holden P, Keene DR, Lunstrum GP, Bachinger HP, Horton WA (2005) Secretion of cartilage oligomeric matrix protein is affected by the signal peptide. J Biol Chem 280:17172-79. Cho JY, Guo C, Torello M, Lunstrum GP, Iwata T, Deng C, Horton WA (2004). Defective lysosomal targeting of activated FGFR3 in achondroplasia. Proc Natl Acad Sci 101:609-14. Horton WA (2003). Skeletal development: insights from targeting the mouse genome. Lancet 362:560-9.
For more information on publications, contact the faculty member or search PubMed.
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