The long-term objectives of these studies continue to be understanding the molecular basis of assembly of specific tissue and organ structures, i.e. morphogenesis. Work of the previous period of funding has demonstrated that tissue-dependent expression of transcript and protein variants of non-fibrilar collagens (types IX, XII, XIV, and XVIII) determines the microarchitecture of extracellular matrix in different tissues. For the next project period a combination of DNA cloning, immunohistochemistry, protein chemistry and crystallography, cell culture studies, and transgenic mice technology will be used to analyze the interaction properties, processing and function(s) of the nonfibrillar collagen XVIII, and the basis for the inhibitory effects on endothelial cell proliferation and tumor growth in mice associated with a proteolytic fragment, endostatin. Linkage mapping, candidate gene cloning, mutation detection and analyses of transgenic mice will provide the basis to further examine the role of a receptor tyrosine kinase signal transduction pathway in regulating the interaction between endothelial cells and their underlying extracellular matrix. These studies will contribute significantly to the understanding of normal tissue and organ morphogenesis and provide a basis for improved therapeutic strategies in disease processes of tissue repair, cancer and genetic abnormalities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
2R01AR036820-14
Application #
2696886
Study Section
Pathobiochemistry Study Section (PBC)
Project Start
1985-07-01
Project End
2003-06-30
Budget Start
1998-07-20
Budget End
1999-06-30
Support Year
14
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Harvard University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Hu, Kai; Olsen, Bjorn R (2017) Vascular endothelial growth factor control mechanisms in skeletal growth and repair. Dev Dyn 246:227-234
Olsen, Bjorn R; Berendsen, Agnes D; Besschetnova, Tatiana Y et al. (2016) Fell-Muir Lecture: Regulatory mechanisms of skeletal and connective tissue development and homeostasis - lessons from studies of human disorders. Int J Exp Pathol 97:296-302
Agarwal, Shailesh; Loder, Shawn; Brownley, Cameron et al. (2016) Inhibition of Hif1? prevents both trauma-induced and genetic heterotopic ossification. Proc Natl Acad Sci U S A 113:E338-47
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Duncan, Michael B; Yang, Changqing; Tanjore, Harikrishna et al. (2013) Type XVIII collagen is essential for survival during acute liver injury in mice. Dis Model Mech 6:942-51
Adams, Allysa; McBratney-Owen, Brandeis; Newby, Brittany et al. (2013) Presphenoidal synchondrosis fusion in DBA/2J mice. Mamm Genome 24:54-62

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