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PD Dr. Michael Willem

Head of the Research Group Alpha- and Beta-Secretase

Affiliation

Ludwig-Maximilians University Munich &
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V., Metabolic Biochemistry

Contact

Ludwig-Maximilians University Munich &
Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) e.V.
Feodor-Lynen Strasse 17
D- 81377 München

Phone: +49 (89) 4400 - 46533
Fax: +49 (89) 4400 - 46546

Website: http://www.biochemie.abi.med.uni-muenchen.de/about/staff/senior_scientists/willem/index.html
Website: http://www.biochemie.abi.med.uni-muenchen.de/haass/alpha-beta-secretase/index.html

Research Focus

The Laboratory for Neurodegenerative Disease Research focuses on the generation of Amyloid ß-peptide (Aß) as the major constituent of neurotoxic amyloid plaques in Alzheimer's Disease (AD). Proteolytic processing of an amyloid precursor protein (βAPP) by β- and γ-secretases leads to Aß, whereas βAPP cleavage by α-secretases prevents Aß formation. In order to identify cellular mechanisms involved in the physiological and pathophysiological regulation of AD secretases, the group of Dr. Willem studies the function, expression, subcellular localization and the influence of trafficking and sorting of β- secretase (BACE1) by using transgenic mouse models. Some key topics addressed in the lab regarding the understanding of BACE1 function in physiological and pathophysiological conditions, especially in AD, are:

- Biochemical identification of new proteolytic substrates of the beta-Secretase BACE1

- Immunohistological subcellular localization of compartments in which BACE1 cleaves the substrates

- Analysis of expression and functions of BACE1 substrates in control mice and BACE1 KO mice

- Transcriptional and translational regulation of BACE1 in cultured cells (e.g. HEK293 and primary neurons) and in the CNS

Primary Technique(s): subcellular localization of beta-amyloid precursor proteins, enzyme activity manipulation

Model Organism(s): transgenic mice