Understanding Bone Biology Through the Discovery of Osteogenic Proteins Derived From the Study of Craniosynostosis
Craniosynostosis, the premature fusion of the skull bones, is a significant medical and dental health issue. The Cunningham Lab is investigating the molecular and developmental causes of isolated and hereditary craniosynostosis syndromes, with the goal of understanding what drives premature bone fusion. Using RNA sequence data from cell lines derived from surgical bone samples from craniosynostosis patients and controls, Dr. Michael L. Cunningham is evaluating the role of differential gene expression and the contribution of genetic variants to the disease.
Dr. Michael L. Cunningham
In addition to identifying causal mutations in craniosynostosis, this work is aimed at gaining an understanding of the biology of bone growth and how disease disrupts the maintenance of normal bone development. Using differential gene expression data and studies on the mechanobiology of osteoblasts, Cunningham is focused on identifying factors that affect bone growth. Recently, the Cunningham Lab and collaborators have identified a relationship between insulin growth factor 1 (IGF1) activation and changes in cellular contractility and migration in osteoblasts derived from craniosynostosis patients.
The discovery of osteogenic proteins may have important therapeutic implications for the treatment of fractures, osteoporosis, bony overgrowth and in the management of surgical wounds. Ultimately, it may be possible to develop therapeutics to treat bone disorders and congenital abnormalities or for use as adjuvants in surgical procedures involving the need to regrow bone or modulate the rate of bone growth. Cunningham is interested in potential industry collaborations where his expertise in bone biology would contribute to the identification of proteins involved in bone formation and the regulation of bone growth, as well as in proteins with potential clinical utility in the treatment and management of bone disorders and malformations.
Stage of Development
- Pre-clinical in vitro
- Pre-clinical in vivo
- Collaborative research opportunity
- Sponsored research agreement
- Tissue sample access
- Consultation agreement
- Park SS, Beyer RP, Smyth MD, Clarke CM, Timms AE, Bammler TK, Stamper BD, Mecham BH, Gustafson JA, Cunningham ML. Osteoblast differentiation profiles define sex specific gene expression patterns in craniosynostosis. Bone. 2015; 76:169-176.
- Stamper BD, Mecham B, Park SS, Wilkerson HW, Farin FM, Beyer RP, Bammler TK, Mangravite LM, Cunningham ML. Transcriptome correlation analysis identifies two unique craniosynostosis subtypes associated with IRS1 activation. Physiol Genomics. 2012; 44(23):1154-1163.
- Stamper BD, Park SS, Beyer RP, Bammler TK, Farin FM, Mecham B, Cunningham ML. Differential expression of extracellular matrix-mediated pathways in single-suture craniosynostosis. PLoS One. 2011; 6(10):e26557. PMCID: PMC3197523.
To learn more about partnering with Seattle Children’s Research Institute on this or other projects, please contact:
Dr. Elizabeth Aylward
Director, Office of Science-Industry Partnerships