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| Research Interests |
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Dr. Jacenko's laboratory is investigating processes that control skeletal development, which proceeds predominantly by replacement of cartilage with bone and marrow. These transitions occur during embryonic and post-natal skeletal growth, and are altered in most skeletal disorders. To test the role of collagen X, a molecule expressed only in mature cartilage preceding its replacement, transgenic mice were generated expressing a defective variant of this protein. Resultant mouse skeletal defects helped identify a human disorder (dwarfism) resulting from collagen X mutations. Furthermore, intriguing and acute hematopoietic and immune abnormalities suggested a novel hypothesis that cartilage substitution by marrow establishes the prerequisite environment for blood cell development; this represents a previously unforseen link between skeletal development and hematopoiesis.
The multidisciplinary approach of the laboratory addresses mechanisms of skeletal development and blood cell differentiation through transgenesis, molecular biology, biochemistry and immunology. Our short-term goals include: 1) identification of mechanism(s) by which abnormal collagen X molecules cause skeletal deformities and marrow defects in mice and humans; 2) analysis of marrow and blood defects causing immune deficiency and lymphosarcomas in mice transgenic for collagen X; and 3) characterization of the marrow stromal environment that is prerequisite for hematopoiesis; and 4) investigating the role of cell cycle in the cartilage-to-bone/marrow transition, and in the establishment of the bone marrow. Results may elucidate mechanistic links between bone and blood development, and provide a genetic basis for certain skeletal, hematopoietic, immunologic, and/or metastatic disorders in humans. The ability to distinguish between disease mechanisms will prove invaluable for therapies. |
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| Selected Publications
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- Jacenko, O., Campbell, M.R., Roberts, D.W. Linking endochondral ossification to hematopoiesis, Bone and Mineral Research, In Press.
- Jacenko, O., Roberts, D.W., Gress, C.J., Campbell, M.R., and Tao, Z. Linking hematopoiesis to endochondral skeletogenesis through analysis of mice transgenic for collagen X, Am. J. Pathol. In Press.
- Jacenko, O., Chan, D., Franklin, A., Ito, S., Bateman, J., and Campbell, M. A dominant interference collagen X mutation disrupts hypertrophic chondrocyte pericellular matrix, and glycosaminoglycan and proteoglycan distribution in transgenic mice, Am. J. Pathol. In Press.
- Healy, C., de Crombrugghe, B., Jacenko, O., (2000), Growth plate compressions and altered hematopoiesis in collagen X null mice, J. Cell Biol., 149:983-993.
- Chan, D. and Jacenko, O. (1998), Phenotypic and biochemical consequences of collagen X mutations in mice and humans (Review). Matrix Biol., 17:169-184.
- Jacenko, O., LuValle, P., and Olsen, B.R. (1993), Spondylometaphyseal dysplasia in mice carrying a dominant negative mutation in a matrix protein specific for cartilage-to-bone transition. Nature 365:56-61.
- Jacenko, O., Ito, S. and Olsen, B.R., (1996), Skeletal and hematopoietic defects in mice transgenic for collagen X. Ann. N.Y. Acad. Sci. 785:278-280.
- Jacenko, O., (1997), Strategies in generating transgenic mammals. In: Recombinant gene expression protocols, (R.S. Tuan, ed.), Methods Molec. Biol. 62: 399-424.
- Jacenko. O., (2000), Genetic-engineered models of skeletal diseases. I. Collagen Type X. Methods Molec. Biol., 137:471-490.
- Jacenko, O., (1995), c-fos and bone loss: a regulator of osteoclast lineage determination, BioEssays 17: 277-281.
- Jacenko, O., Olsen, B.R., and Warman, M.L. (1994), Of mice and men: heritable skeletal disorders. Am. J. Hum. Genet., 54:163-168.
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