Dr. Sheila Nielsen-Preiss

Associate Research Professor

Osteoblastic mineralization
Effects of microgravity on cellular function

The primary research emphasis of the lab is to understand how osteoblasts control the process of mineralization by elucidating the role of membrane microdomains in signaling and protein sequestration.

In our lifetime, many will suffer from diseases that are commonly associated with defective cellular mineralization. These diseases range from osteoporosis, with a reduction in bone and mineral content, to those with an inappropriate increase in mineralization, such as arthritis and atherosclerosis. These diseases certainly involve inappropriate maintenance and maturation of progenitor cells, but may also involve defects in the ultimate function of the cell. Mineralization is a complex process that requires temporal and spatial regulation of specific proteins. The mechanisms by which osteoblastic cells regulate mineralization, the ultimate step in differentiation, are being investigated. Annexin 2 has been identified as an important protein in the regulation of osteoblastic mineralization. Annexin 2 enhances the mineralization capacity of matrix vesicles by increasing, at least in part, the activity of alkaline phosphatase. Annexin 2 has been localized to specialized membrane domains referred to as lipid rafts, where it co-localizes with, and increases the activity of, alkaline phosphatase. Lipid rafts serve as docking platforms for functional units of proteins and when lipid raft integrity is disrupted, mineralization potential is compromised. We propose that lipid rafts serve as platforms for signaling involved in regulating the cellular content and for sequestering proteins required for subsequent osteoblastic mineralization. The intracellular mechanisms by which mineralization is controlled are likely conserved, therefore characterization in osteoblasts may provide insight into osteoblast-related diseases such as osteoporosis, but may also contribute to the understanding of inappropriate mineralization in other cell types during disease.

A very specialized bone deficiency occurs in astronauts, where they lose 1-2% of their bone mineral density every month they are in space. We hypothesize that part of the osteoblastic failure is due to alterations in cellular polarity and mineralization that occurs in a polarized fashion. In addition to evaluating the effects of simulated microgravity directly on human osteoblastic cells, we are using microgravity-induced changes observed in yeast cell polarity as a model system to better understand and interrogate the mammalian system.

Selected Publications

Gillette, J.M., R.U. Ayers, S.M. Nielsen-Preiss. 2007. Annexin 2 enhanced osteoblastic mineralization mediated by matrix vesicles. In review.

Gillette, J.M., C.P. Gibbs, S.M. Nielsen-Preiss. 2007. Establishment and characterization of OS 99-1, a cell line derived from a highly aggressive primary human osteosarcoma. In review.

Altenburg, S.D., S.M. Nielsen-Preiss, L.E. Hyman. 2007. Increased filamentous growth of Candida albicans in simulated microgravity. Genomic. Proteom. Bioinformatic. In Press.

Nielsen-Preiss, SM, Allen, M.P., M. Xu, D.A. Linseman, J.E. Pawlowski, R. Bouchard, B.C. Varnum, K.A. Heidenrich, M.E. Wierman. 2007. Adhesion related kinase (Ark) induction of migration requires PI3-kinase and Ras stimulation of Rac activity in immortalized GnRH neuronal cells. Endocrin. 148: 2806-2814.

Shorts-Cary, L., M. Xu, J. Ertel, B.K. Kleinschmidt-Demasters, K. Lillehie, I, Matsuoka, S. Nielsen-Preiss, M.E. Wierman. 2007. Bone morphogenetic protein and retinoic acid-inducible neural specific protein-3 is expressed in gonadotrope cell pituitary adenomas and induces proliferation, migration, and invasion. Endocin. 148: 967- 975.

Ayers,R., S.M. Nielsen-Preiss, V. Ferguson, G. Gotolli, J. J. Moore, H-J Kleebe. 2006. Osteoblast-like cell mineralization induced by multiphasic calcium phosphate ceramic. Material Sci & Engineer. C26:1333-1337.

Gillette, J.M. and S.M. Nielsen-Preiss 2004. Downregulation of Annexin 2 in Human Osteosarcoma Metastasis. J Cell Biochem 92:820-832.

Wierman M.E., J.E. Pawlowski M.P., Allen, D.A. Linseman, M. Xu, and S. Nielsen- Preiss. 2004. Molecular mechanisms of gonadotropin-releasing hormone neuronal migration. Trends Endocrin Metab. 15:96-102.

Gillette, J.M. and S.M.Nielsen-Preiss. 2004. The role of annexin 2 in osteoblastic Mineralization. J Cell Sci 117:441- 449.

Nielsen-Preiss, S.M., S.R. Silva and J.M. Gillette. 2003. Role of PTEN and Akt in the regulation of growth and apoptosis in human osteoblastic cells. J Cell Biochem 90 (5) 964-975. (cover article).

Nielsen-Preiss, S.M., J. P. Quigley, J. E. Testa. 1999. Co-inoculation of human and murine carcinoma cells induces reciprocal suppression of metastasis by both cell lines. Clin. Exp. Metastasis 17 (6) 489-49.

Nielsen-Preiss, S. M., J.P. Quigley. 1993. Detection of low abundant cellular proteins that specifically increase upon loss of the metastatic phenotype. J. Cellular Biochem. 52:219-235.

Education

Affiliations

Former lab members

Jennifer Gillette, PhD from University of Colorado HSC in 2004; currently a postdoctoral fellow at the NIH.

Selina Silva, MD from University of Colorado HSC in 2005; currently an orthopaedic resident at the University of New Mexico.

Shapir Rosenberg, Math and Science teacher at Maimonides, Brookline, MA and in Jerusalem, Israel.

Sarah Stroh, BS from University of Colorado at Boulder 2004; currently a research assistant at the University of Colorado HSC.

Chris Ruzas, currently a medical student at the University of Colorado HSC.

Srinivas Iyengar, MD from University of Colorado HSC 2005; currently an Ophthamalogy resident at the University of Colorado HSC.

Return to regular view	Text-only	Updated: 9/27/2007