- Early Stage Researcher, University of Hong Kong
- WP4: Impact of ECM and oxygen tension on the interaction of osteogenesis and angiogenesis
- Secondment to ERASMUS, September-December 2019
William Lam is a PhD student in the School of Biomedical Sciences at the University of Hong Kong under the supervision of Professor Danny Chan. His study is focusing on understanding the molecular details behind the pathologies of a rare genetic bone disease called Osteogenesis Imperfecta type V (OI-V). OI-V is caused by a point mutation at the 5’ UTR of IFITM5. The typical pathology is bone fragility and banding, with three characteristic phenotypes, formation of hyperplastic callus during fracture healing, interosseous membrane ossification, and mesh-like bone lamellae. To understand how the expression of the mutant gene is linked to the pathogenesis, he utilizes a cell line system which allows an inducible overexpression of either the wildtype or mutant ifitm5. By understanding the cellular changes during different stages of osteogenic differentiation when mutant or wildtype IFITM5 expression is induced, we may obtain some molecular insight on the function of normal IFITM5, and how the effect of the mutation changes cell physiology.
There were three objectives for the secondment. The first was to study whether the expression of mutant ifitm5 affects the formation and organization of ECM, and whether the putative changes in ECM organization play a significant role in the difference in in vitro mineralization between wildtype and OI-V primary patient osteoblasts.
The second objective was to learn how to isolate and purify extracellular vesicles (EVs) from osteoblasts. Mineral and matrix vesicles are considered to be major players in ECM mineralization, and therefore may be accountable for the difference in in vitro mineralization.
The last objective was to learn how to culture osteocytes and possibly, generate OI-V mutant osteocytes.