PD Dr. Michael Schwake

CV/Research Experience

Since 02/2013  Group leader at the Department of Chemistry, Biochemistry III in Bielefeld with Prof. G. Fischer von Mollard

2016 - 2020     Visiting Professor at the Department of Neurology, Northwestern University Feinberg School of Medicine

2007 – 2013    Group leader at the Department of Biochemistry in Kiel

2007                Habilitation in Biochemistry (Christian-Albrechts-University of Kiel)

2002 - 2007     Scientific Assistant at the Department of Biochemistry in Kiel with Prof. P. Saftig

2002                Research Associate with Prof. S. Pfeffer, Stanford University, USA

2001                Ph.D. (Free University of Berlin)

1997 - 2001     Dissertation with Prof. T. Jentsch at the Centre for Molecular Neurobiology, Hamburg

1997                Diploma (Biochemistry, Free University of Berlin)

Research

We are interested in studying causative genes for inherited neurological and muscular diseases and to understand their molecular pathology, which is in many cases also relevant for related sporadic diseases.

 

Channelopathies

We are focusing on channelopathies, which are a heterogeneous group of disorders resulting from mutations in genes encoding ion channels. For example, mutations in the genes encoding the voltage-gated potassium channels KCNQ2 and KCNQ3 have been identified in benign neonatal familial convulsions, an autosomal dominant epilepsy of infancy. These channels contribute to the native muscarinic-sensitive potassium current that regulates excitability of numerous types of neurons. We were able to characterize the molecular mode of action for the novel anticonvulsant drug retigabine, which is in clinical use for the treatment of a broad spectrum of epilepsies. More recently, we have been involved in the identification and functional characterization of mutations in an NMDA receptor subunit as a major genetic risk factor for idiopathic focal epilepsy.

DFG-funded projects:

https://gepris.dfg.de/gepris/projekt/5412410?context=projekt&task=showDetail&id=5412410&

https://gepris.dfg.de/gepris/projekt/59533247

https://gepris.dfg.de/gepris/projekt/181163549

 

SNAREopathies

Given our strong interest in epilepsies, we initiated various projects on progressive myoclonus epilepsies (PME), which present with action myoclonus, tonic-clonic seizures and progressive neurological decline. PMEs are predominantly autosomal recessive inherited and have very similar clinical manifestations but are genetically heterogeneous. For example, we have recently identified loss of function mutations in GOSR2 and BET1, SNARE [soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor] proteins that are involved in ER to Golgi transport. Interestingly, recessive mutations in both genes can also cause congenital muscular dystrophy. How mutant GOSR2 and BET1 contribute to disease pathogenesis is unclear and we are currently studying the neurophysiological and muscular role of GOSR2 and BET1 by analyzing mouse models and patient-derived cells.

DFG-funded projects:

https://gepris.dfg.de/gepris/projekt/262447144

 

Lysosomal storage disorders

Another example and our main current research interest is the lysosomal integral membrane protein type 2 (LIMP-2) also named SCARB2 that belongs to the Scavenger receptor family. Null-mutations in SCARB-2, the gene encoding LIMP-2 were found to be responsible for Action Myoclonus-Renal Failure Syndrome (AMRF), a rare disorder characterized by presence of PME in combination with focal glomerulosclerosis. The role of LIMP-2 in the development of AMRF and PME, respectively is so far unkown and topic of our ongoing research. We could also demonstrate that LIMP-2 acts as a lysosomal transport receptor for glucocerebrosidase (GCase), the enzyme defective in Gaucher disease (GD), the most common lysosomal storage disorder. This pathways is exceptional in lysosomal trafficking of lysosomal enzymes that mostly take another route to lysosomes. By solving the crystal structure of the ectodomain of LIMP-2, combined with structural and functional analyses, we identified helical motifs within LIMP-2 and GCase that mediate the specific interaction of both proteins.

DFG-funded projects:

https://gepris.dfg.de/gepris/projekt/468736715

https://gepris.dfg.de/gepris/projekt/277013906

https://gepris.dfg.de/gepris/projekt/43168683

 

Motivated and dedicated students at all levels are always welcome to join our research efforts!

 

We are very grateful for the generous support of our research by the German Research Foundation (Deutsche Forschungsgemeinschaft)

Teaching

Link zum eKVV

 

205007 Molekulare Grundlagen der Biomedizin

210231 Biochemie I Vorlesung & Übungen

210251 Gentechnologie/Mikrobiologie

210252 Gentechnologie/Mikrobiologie

210253 Gentechnologie/Mikrobiologie

 

210243 Biochemie II - Praxis

211121 Zellbiochemie - Praxis

210252 Gentechnologie / Mikrobiologie - Praxis

 

212270 Joint Seminar: Biochemie

 

Publications

 

ORCID:

https://orcid.org/0000-0002-4173-2166

 

Pia Ferle (PhD student)

Kerstin Glüsenkamp (Research technician)

Meike Grosse Venhaus (PhD student)

Robin Genz (Research technician trainee)

Katharina Hirn (Master student)

Luisa Schmidt (Master student)

Charlotte Pleuger (Master student)

Leonie Schröder (PhD student in cooperation with D. Krainc, Chicago)

PostDocs

Judith Koliwer (Principal consultant, Körber Pharma)

Ming Lin (PostDoc, Ohio State University)