Föreläsningar och seminarier Pediatric Oncology seminar

Title: Understanding skeletal late-effects caused by radiotherapy
 

Summary: Children receiving radiotherapy during cancer treatment are highly susceptible to radiotherapy’s side-effects. Because they are still growing radiation can cause skeletal disorders including short stature, irregular body proportions and spinal curvature (Mäkipernaa, A. et al., Eur. J. Pediatr. 152, 197–200 (1993)). One reason why radiotherapy can cause skeletal malformations is that radiation directly damages the cells that allow bone growth: growth plate chondrocytes. Interestingly, bone growth may continue in an impaired fashion, but the underlying mechanisms of this recovery are poorly understood. Efforts to understand and prevent radiation-induced skeletal disorders are currently hampered by the lack of suitable laboratory models. 

In my project, I have firstly established the minimal dose required to cause growth retardation in mice. In order to explore the process by which radiation impairs growth, I have been monitoring the behavior of individual chondrocytes using the Confetti model of clonal genetic tracing (Snippert et al. Cell. 1;143(1):134-44 (2010). This model has allowed me to show that radiation causes impaired growth by preventing growth plate chondrocytes from forming growth columns, something essential for bone elongation. Most interestingly, I have found that some growth plate chondrocytes are able to compensate for the damaged cells and produce a significantly elevated number of columns when given time to recover. With my ongoing experiments, I aim to determine the underlying molecular mechanisms regulating this healing process.

Moderator: Shanie Saghafian-Hedengren