Header Wanker Lab

E. Wanker Lab

Proteomics and Molecular Mechanisms of Neurodegenerative Diseases

Profile

Huntington's disease is a severe neurodegenerative illness. It is at the heart of my lab's activities. Our second major research focus is interactomics - the investigation of proteins interacting with other proteins. Most of the time we connect the two topics: trying to understand Huntington's disease by studying the interactions of the huntingtin protein. Or: mapping the interactome of many proteins to extract insight into the biological networks relevant to neurodegenerative disease.

The vinegar fly - Drosophila melanogaster by its zoological name - is a model organism that helps us understand how the disease affects nerve cells in the brain. 

Confocal microscopy image of a Drosophila brain in which expression of huntingtin with an elongated polyglutamine sequence was turned on for 6 days and turned off for the 18 days that followed. Red: synapses present in all neuronal cells. Green: huntingtin aggregates that form and deposit in the brain.

We have established HD fly models that enable the in vivo investigation of the huntingtin protein, its aggregation and seeding specifically in neurons. See: Anne Ast et al. “mHTT Seeding Activity: A Marker of Disease Progression and Neurotoxicity in Models of Huntington's Disease”. Molecular Cell. 2018 Sep 6;71(5):675-688.e6. https://doi.org/10.1016/j.molcel.2018.07.032.

 

More about our research:

Millions of people worldwide suffer from neurodegenerative disorders, like Alzheimer’s, Parkinson’s or Huntington’s disease. Most of these illnesses break out later in life. Correlated to the current demographic shift towards aging societies in many countries, the number of people affected with neurodegenerative diseases is growing.

Still, we do not understand exactly how neurodegenerative diseases develop. One of the characteristic features many neurodegenerative diseases share is the deposition of abnormally folded proteins in patient brains.

My group's research focusses on ‘Neuroproteomics’, the protein-based investigation of neurodegenerative diseases. We aim to elucidate the molecular principles by which proteins, sometimes abnormally folded, alone or in interaction, lead to cellular toxicity and neuronal dysfunction, causing neurodegeneration.

We pursue two main lines of investigation: Hypothesis-driven molecular studies of protein misfolding, aggregation and spreading, on the one hand, unbiased protein-protein interaction or ‘interactomics’ studies on the other. Click "Research" above to read about our current projects and fields of interest.

 

Team

Prof. Erich Wanker, PhD, DI

Principal Investigator

+49/30/9406-2157
ewanker@mdc-berlin.de

 

Orchid Wael Mostapha Ammar, MSc

Graduate student

+49/30/9489-2147
orchid.ammar@mdc-berlin.de

 

Stephanie Beetz, MSc

Technician

+49/30/9489-2138
stephanie.beetz@mdc-berlin.de

 

Annett Böddrich, PhD, Dipl. Biol.

Senior scientist, project manager

+49/30/9406-2357
a.boeddrich@mdc-berlin.de

 

Megan Bonsor, MSc

Graduate student

+49/30/9406-3421
megan.bonsor@mdc-berlin.de

 

Lydia Brusendorf, DI

Technician

+49/30/9406-2636
lydia.brusendorf@mdc-berlin.de

 

Annika Deckert, PhD, MSc

Postdoc, Alzheimer's Association Research Fellow

+49/30/9489-2147
annika.deckert@mdc-berlin.de

 

Bastien Farcy

Graduate student

+49/30/9406-2360
bastien.farcy@mdc-berlin.de

 

Christian Hänig, DI

Computational scientist, IT, automation

+49/30/9406-2437
c.haenig@mdc-berlin.de

 

Nancy Neuendorf, BTA

Senior technician

+49/30/9406-2805
nancy.neuendorf@mdc-berlin.de

 

Roxane Maria Papawassiliou, MSc

Graduate student

+49/30/9406-2805
roxanemaria.papawassiliou@mdc-berlin.de

 

Eduardo Silva Ramos, PhD, MSc

Postdoc

+49/30/9489-2138
eduardo.silvaramos@mdc-berlin.de

 

Leonard Roth

Graduate student

+49/30/9406-2360
leonard.roth@mdc-berlin.de

 

Sarina Rudolf, DSc

Postdoc

+49/30/9406-2433

sarina.rudolf@mdc-berlin.de

 

Annabell Salzmann

Graduate student

+49/30/9406-2360

annabell.salzmann@mdc-berlin.de

 

Nadine Scharek

Technician

+49/30/9406-2433
nadine.scharek@mdc-berlin.de

 

Sigrid Schnögl, MPhil, MBA

Coordinator

+49/30/9406-2357
sigrid.schnoegl@mdc-berlin.de

 

Frederick Wieshmann

Graduate student

+49/30/9406-2360
frederick.wieshmann@mdc-berlin.de

 

Martina Zenkner, DI

Senior technician, lab manager

+49/30/9406-2357
zenkner@mdc-berlin.de

 

Claudia Abraham

Mohammed Ahmed

Anna-Clara Amler

Kathrin Andrich, PhD

Iris Apostel-Krause

Anup Arumughan, PhD

Vinayagam Arunachalam, PhD

Anne Ast, PhD, MSc

Jennifer Doreen Augsten

Katrin Bagola

Bianca Bauer

Irem Bayraktaroglu

Lynn van der Beek

Simon Berberich

Annaporna Bhat

Jan Bieschke, PhD

Malla Bimalla

Nicole Bock

Svenja Bolz

Anne Borowski

Marta Botelho

Lamia Bouguerne

Nisrin Nora Boukantar

Yacine Bounab, PhD

Anja Briese

Raul Bukowiecki

Alexander Buntru, PhD

Anne Busch, PhD

Branca Cajavec

Morena Cauglia

Irene Carod

Laura Benitez Casanova

Gautam Chaurasia, PhD

Ummi Hadiba Ciptasari

Louica Delius

Monishita Dey

Ina Dieckmann

Nea Dierolf

Lisa Diez, PhD

Franziska Dinter

Christin Donner

Ulrike Drewes

Anja Dröge, PhD

Juliane Edel, Master

Dagmar Ehrnhöfer, PhD

Thomas Ehrnhöfer

Sabine Engemann, PhD

Figen Ertas

Claudia Eulenberg

Maik Faltysek

Claudia Felsch

Christian Fink, PhD

Carina Fischer, MSc

Leonhard Fister

Alexandra-Iona Forrai

Raphaele Foulle

Ralf Friedrich, PhD

Clemens Franke

Anja Fritzsche

Joris Geigenmüller, BSc

Klaus Genser, PhD

Heike Göhler, PhD

Sabrina Golusik, BTA

Gerlinde Grelle

Saskia Gressel

Nicole Groenke

Mirjam Groh

Anja Guhra

Stephanie Haase

Ulrike Hagen

Anne Hahmann

Tobias Hahn, MSc

Mohamed Haji, MSc

Lilli Hammermüller

Anna Happe-Kramer

Renate Hasenbank

Regine Hasenkopf

Antje Haug

Denise Heidler

Michael Henriksen

Markus Hensel, BTA

Martin Herbst, PhD

Christin Hesse

Sarina Hilke, Technician

Yen Trang Hoang

Sheila Hoffmann

Sabine Horn

Inna Hoyer

Ulrike Hübner

Melanie Humpenöder

Ismail Ishola, PhD

Manuela Jacob

Philipp Jäger, PhD

Marina Jahns

Isabelle Jansen

Sha Jin, PhD

Carmen Judis

Ronny Kalis

Sedef Karayel

Stefanie Kasper

Tina Kausel

Irem Kaymak, Trainee

Birgit Kersten, PhD

Christopher Kessler

Daria Kiesel

Sylvia Kietzmann

Loni Klaus

Daniela Kleckers

Konrad Klockmeier, MSc

Maria Knoblich

Young-In Ko, PhD

Matthias Könn, PhD

Susanne Köppen

Marja Kornhuber

Susanne Kostka

Simona Kostova, PhD, MSc

Manuel Krispin

Jeffrey Kroetsch, PhD

Sabrina Kruse

Christin Kuschke

Evangelos Kyriazidis, Trainee

Maciej Lalowski, PhD

Hans Lehrach jr.

Iva Lelios

Megan Leong

Anna Lewandowski

Rahel Lewin

Mara Liebich, TA

Carmen Lorenz-Brunne, PhD

Elena Lucas

Barbara Lucke

Marie Lütke-Eversloh

Melanie Manzke

Phoebe Markovic, PhD

Stefan Maul

Sonia Mazzitelli

Benjamin McMahon

Sascha Mintzlaff

Angeli Möller, PhD

Annekathrin Möller, PhD

Katja Mühlenberg, PhD

Eva-Christina Müller, PhD

Stanley Myers O’Mulloy

Sandra Neuendorf

Cecilia Nicoletti

Hannah Niederlechner, MSc

Julia Niepelt

Anna Norton

Yetunde Odunsi

Leon Olivier

Albrecht Otto, PhD

Inken Padberg

Mary Paniscus, MSc

Adrián Martí Pastor

Christine Petersen, PhD

Spyros Petrakis, PhD

Vanessa Pfiffer

Maria Lucia Pigazzini

Erika Pisch

Stephanie Plassmann, PhD

Pablo Porras Millan, PhD

Anita Pras

Ellen Ramminger, PhD

Tamas Rasko, PhD

Kirstin Rau

Susanne Rautenberg

Alexandra Redel

Sean-Patrick Riechers, PhD

Uli Rockenbauch

Susanne Rohn

Eugenia Rojas

Maxi Rothbart

Dana Rotte

Jenny Russ, PhD

Natalja Rutz

Linda Salzwedel

Maria Saßning

Kati Scharf

Franziska Schiele

Franziska Schindler, PhD, MSc

Philipp Schleumann

Sebastian Schmid

Michael Schmidt, PhD

Vera Schmiedel

Stefanie Schneider

Anke Schönherr

Eileen Schormann

Nadja Schräpel

Herwig Schüler, PhD

Margitta Schümann

Paul Schultze-Motel, PhD

Aline Schulz, PhD

Sabrina Schulz

Erik Schweitzer, PhD

Christopher Secker, Dr. med.

Derya Sen

Leticia Serra

Maliha Shah, PhD

Luke Southan

Silke Spading

Selma Staege

Uli Stelzl, PhD

Kerstin Stemmer

Kathrin Stilz

Nadine Strempel, PhD

Sarah Stricker, MD

Martin Strödicke, PhD

Jaana Suopanki-Lalowski, PhD

Bernhard Suter, PhD

Babila Tachu, PhD

Anne Tempelmeier

Pallavi Thaore

Lasse Thiem

Anke Thieme

Jan Timm

Engin Toksoez

Philipp Trepte, PhD

Sofie Trummer

Julia Ucar

Ella Ullerich

Patrick Umbach, PhD

Jose Miguel Urquiza

Tobias Vöpel, PhD

Stephanie Wälter, PhD

Anne Wagner, PhD

Lia Walcher

Emily Walker

Jacqueline Walter

Katja Welsch, PhD

Ina Wendland, undergraduate student

Carsta Werner

Franziska Wiedemann

Thomas Wiglenda, PhD

Lindsay Willmore

Sascha Wiswedel

Heike Wobst

Uwe Worm

Sargon Yigit

Oleksandr Zabiegalov

Joshua Zelwis

Jana Zielinski

Research

My group's research focusses on ‘Neuroproteomics’, the protein-based investigation of neurodegenerative diseases. In detailed, hypothesis-driven studies we address mechanisms of protein misfolding and aggregation, with the aim of understanding the molecular mechanisms of neurodegeneration in Huntington’s, Alzheimer’s and further diseases causally related to the misfolding of proteins. Our second field of activity is interactomics, which we also mainly apply to neurodegenerative disease processes.

In particular, we aim to elucidate the molecular principles by which abnormally folded proteins, their complexes and aggregates cause cellular toxicity and neuronal dysfunction. In our efforts to promote translation of basic research into benefits for patients, we identify and characterize modulators of protein misfolding cascades in disease (Ehrnhoefer et al., Nat Struct Mol Biol, 2008; Bieschke et al., Nat Chem Biol, 2011). We have previously demonstrated that expanded polyglutamine (polyQ) sequences trigger misfolding and aggregation of N-terminal huntingtin fragments in vitro and in vivo (Scherzinger et al., Cell, 1997; Davis et al., Cell, 1997). More recently, we have started new lines of translational research establishing methods to detect disease-relevant misfolded protein species in biosamples from models and patients. These investigations are directed at developing predictive disease markers that are a prerequisite for the clinical investigation of new disease-modifying therapies targeting neurodegeneration before symptoms of irreversible neuronal damage arise.

With our interactomics activities, we have developed an automated yeast two-hybrid (Y2H) system, which we used to generate a focused protein-protein interaction network for the huntingtin protein relevant to Huntington's disease (Goehler et al., Mol. Cell, 2004), as well as a large interaction map of the human proteome (Stelzl et al., Cell, 2005). More recently, we identified highly relevant interactions between the triple-A ATPase VCP/p97 and an adaptor protein that effects a fundamental structural change in VCP from a homohexamer to a heterooligomer with far-reaching functional implications (Arumughan et al. 2016). We are constantly developing more powerful methods for the identification and validation of protein-protein interactions, most recently LuTHy, a double readout luminescence-based technology for interactome mapping in mammalian cells (Trepte et al., Mol Syst Biol, 2018). A new resource for mapping the interactome of neurodegeneration has been available to researchers since 2020 (Haenig et al., Cell Rep., 2020):

https://www.mdc-berlin.de/news/news/unusual-suspects

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