© F.Schindler, AG Wanker, MDC
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
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
> Previous members <
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):
