Thomas Schmidt, Heike Pawlack, Christoph Max, Karen Grütz, née Freimann, Aloysius Domingo, Ana Westenberger
Thomas Schmidt, Heike Pawlack, Christoph Max, Karen Freimann, Aloysius Domingo, Ana Westenberger

Functional genetics of movement disorders

Ana Westenberger, PhD

Team: Ana Westenberger, PhD (group leader); Aloysius Domingo, MD (visiting scientist, PhD student); Karen Grütz, née Freimann, PhD (Postdoc); Heike Pawlack (research technologist); Thomas Schmidt (MD student); and Christoph Max (MD student)

The research team “Functional genetics of movement disorders” focuses on the identification and functional characterization of the structural and epigenetic DNA changes that lead to the development of various movement disorders. To achieve these goals, we combine linkage analysis with Sanger and next-generation sequencing and real-time quantitative PCR. The identification of DNA changes is followed by a series of molecular biology, cellular biology, and protein biochemistry assays. By this, we examine the consequences of the detected DNA changes on transcriptional regulation of gene expression and on protein translation levels, subcellular localization, stability, and functional interactions of the affected proteins. Finally, we aim to correlate our findings with the observed clinical phenotypes and hypothesize mechanism(s) of disease.

Our current projects investigate the genetic basis of X-linked dystonia-parkinsonism, a form of spinocerebellar ataxia and a form of early-onset Parkinson disease. In addition, we have recently discovered that mutations in the PDGFB gene cause brain calcifications in human (familial idiopathic basal ganglia calcification) and mice. Functionally, we are studying i) the complex interplay between dystonia-associated proteins, and ii) the role of the ubiquitination process in the development of Parkinson disease. 

Importantly, we value and acknowledge scientific exchange and input from our international collaborators Prof. Dr. Henry L. Paulson (University of Michigan, USA), Prof. Dr. Lillian V. Lee and Prof. Dr. Raymond Rosales (XDP study group, Philippines), and Prof. Dr. Vladimir S. Kostic (University of Belgrade, Serbia).
Our projects are funded by the Fritz-Thyssen Foundation, the Bachmann Strauss Dystonia & Parkinson’s Disease Foundation, and intramural grant support.

Figure: Time-course experiments of HEK293 cells stably expressing GFP-Parkin wild-type or one of the mutants and treated with CCCP. GAPDH served as a loading control.