Title: Osteocytes in osteogenesis imperfecta (OI)
Roy Morello is an Associate Professor in the Department of Physiology and Cell Biology at UAMS and served as Director of the Bone Histology and Imaging Core in Phase 1. Until recently, the focus of Dr. Morello’s work has been on identifying additional genes of this type. However, over the last 5 years he has begun to examine the potential role of altered osteocyte behavior in the pathogenesis of OI. Most OI research is focused on the role of OI mutations in osteoblasts since they produce the bulk of the bone matrix. Although this project is not yet supported by extramural funding, he has nonetheless obtained evidence that the transcriptome of osteocytes is dramatically altered in murine models of OI. The overall goal of his COBRE project is to determine to what extent OI mutations directly or indirectly alter the function of osteocytes and thereby contribute to the skeletal changes in OI. To accomplish this, he has created a novel mouse model that will allow him to express a collagen 1 mutation—in osteocytes but not osteoblasts—that is responsible for a severe form of OI in humans. In a complementary set of studies, he will delete Crtap from osteocytes but not osteoblasts. In a final set of studies, Dr. Morello will use scRNA-seq to compare the osteocyte transcriptomes of mice lacking Crtap globally versus specifically in osteocytes. This latter approach should reveal whether changes in osteocytes versus changes in the osteocyte environment, namely bone matrix produced by osteoblasts, are responsible for altered gene expression in osteocytes.
Dr. Morello graduated from COBRE support when his project was funded by an NIH R01 in 2023.