|Place of birth||Heidelberg|
|Date of birth||18.01.1979|
PhD under K. F. Winklhofer, MD PhD at the Adolf-Butenandt Institute, Ludwigs-Maximilians-University, Munich.
|2003/2004||Diploma thesis in the laboratory of Prof.J. Darnell at the Rockefeller University, New York, USA (Supervisor: M. Henrikson, PhD)|
|2000-2001||Erasmus-exchange at the Université de Paris XI (France)|
|1998-2001||Undergraduate studies at the Phillipps-University Marburg
Role of Parkin in Stress Response Pathways
Parkinson’s Disease (PD) is a movement disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. The recent identification of gene mutations responsible for familial PD may advance our understanding of the molecular mecha- nisms underlying neuronal degeneration. Among the genes which are responsible for monogenic familial variants of PD, the parkin gene (PARK2) seems to play a prominent role.
The parkin gene encodes a 465 amino acid protein with an ubiquitin- like domain (UBL) at the N-terminus and two RING finger motifs close two the C-terminus, suggesting that parkin has an E3 ubiquitin ligase activity. Various putative parkin substrates have been reported, however these proteins are highly diverse and so far did not contribute to understand the physiological role of parkin.
We and others observed that parkin has the capacity to protect cells against different stress conditions, including oxidative stress, mito- chondrial and endoplasmic reticulum (ER) stress, however the underlying mechanism is still elusive. My PhD project is focussed on the mechanism of this neuroprotective activity. The goal of the study is to understand the regulation of parkin activity and to identify signaling path- ways involved in the cytoprotective action of parkin. Specifically, I want to address the question of whether parkin can mediate an inter- organelle crosstalk between mitochondria and ER.
Parkin can protect cells from both mitochondrial and ER stress and both organelles play an important role in mediating pro- and anti-apoptotic pathways in response to cellular stress. Based on the protective effect of parkin against ER stress, a possible effect of parkin on ER stress pathways (unfolded protein response, ER-associated degradation) will be addressed.
Insights into the physiological function of parkin and the identification of signaling pathways modulated by parkin may serve as a basis for the development of new therapeutic strategies, which could halt or delay the progression of PD.