Research overview

Our work focuses on secreted molecules designated neurotrophins. These molecules play critical roles in the development of the vertebrate nervous system and the maintenance of its function in the adult (for a recent review of some of their properties, see Dekkers et al. 2013).  The dominant neurotrophin in the CNS is brain-derived neurotrophic factor (BDNF). It is encoded by a gene regulated by neuronal activity and both human genetics and animal models illustrate its relevance in, for example, memory consolidation and neuroprotection. We now explore the possibility that BDNF may regulate not only the function, but also the growth and function of neurons in the adult brain, either from within the brain or from sources outside the brain. Indeed, our laboratory recently identified megakaryocytes as a major source of BDNF in humans, in collaboration with the group of Cedric Ghevaert at the University of Cambridge (see Chacon-Fernandez et al. 2016). We are also interested in using small molecules diffusing into the brain with the goal of increasing BDNF levels so as to help preventing neuronal dysfunction (see Deogracias et al. 2012). Our laboratory extensively uses both mouse and human embryonic stem cells to generate neurons. This represents a powerful tool that based on the use of differentiated mouse embryonic stem cells allowed us to uncover new roles for the transcription factor Pax6 (Nikoletopoulou et al., 2007), the amyloid precursor protein APP (Schrenk-Siemens et al. 2008), the neurotrophin receptors p75 (Plachta et al. 2007; Bischoff et al. 2012), TrkA and TrkC (Nikoletopoulou et al. 2010) and MeCP2, the gene most frequently mutated in Rett syndrome (Yazdani et al. 2012).

Collaborators

• Dr Hayley Dingsdale, Post-doctoral fellow
• Dr Xinsheng Nan, Post-doctoral fellow
• Dr Kate Binley, Post-doctoral fellow
• Spyros Merkouris (PhD student)
• Katharina Saueberli (PhD student)
• Laura Cassels (PhD student)