Rosa Rademakers Lab

Research focus

Research in our group is focused on the discovery and functional characterization of novel disease genes implicated in frontotemporal lobar degeneration (FTLD) and related disorders. FTLD represents 10-20% of all dementias and is clinically important because of its early onset and its dramatic impact on core human qualities, including personality, insight and verbal communication. While significant progress has been made in recent years to improve our understanding of the genetics of FTLD and the pathologies underlying this collection of neurodegenerative diseases, the etiology of the disease remains unknown in more than half of the patients. 

Our group leads world-wide
consortia to identify causal genes and genetic risk factors for two important pathological subtypes of FTLD: FTLD with TDP-43 pathology (FTLD-TDP) and FTLD with FUS pathology (FTLD-FUS). We combine genomic, transcriptomic, epigenomic and proteomic analyses on unique collections of FTLD-TDP and FTLD-FUS brain tissues to identify genes and pathways implicated in disease. We also lead consortia focused on genetic disease modifiers in FTLD patients which are known to carry mutations in GRN and C9orf72 with the goal to identify factors that could explain the large variability in symptom onset, clinical phenotype and disease penetrance in patients with these mutations. Additional studies are focused on collaborative efforts to combine rich collections of human data to study the similarities and differences among neurodegenerative diseases.

Our group also leverages our genetic findings to further the understanding of FTLD and related disorders through the generation of cell and mouse models. Most recently, we are focusing on TMEM106B, a lysosomal protein with relatively unknown function which we found to be the major modifier of disease in patients with GRN mutations. We have generated several Tmem106b mouse models, including Tmem106b CRISPR/Cas9 knock-in mice with possible protective and risk variants. Careful assessments of these mice on wild-type and Grn knock-out backgrounds is ongoing to increase our understanding of TMEM10B and its potential as a therapeutic target.

Through the discovery of novel FTLD disease genes and factors that modify the expression of known disease genes such as GRN and C9orf72, our research provides important new insight into the pathomechanisms underlying FTLD. As such we contribute to a more accurate and earlier diagnosis of FTLD patients, to the development of biomarkers associated with disease phenotype and/or progression and to the identification new targets for neurodegenerative disease therapies. 

Publications

Potential genetic modifiers of disease risk and age at onset in patients with frontotemporal lobar degeneration and GRN mutations: a genome-wide association study.Pottier Cyril Zhou Xiaolai Perkerson Ralph Baker Matt Jenkins Gregory Serie Daniel Ghidoni Roberta Benussi Luisa Binetti Giuliano López de Munain Adolfo Zulaica Miren Moreno Fermin Le Ber Isabelle Pasquier Florence Hannequin Didier Sánchez-Valle Raquel Antonell Anna Lladó Albert Parsons Tammee Finch NiCole Finger Elizabeth Lippa Carol Huey Edward Neumann Manuela Heutink Peter Synofzik Matthis Wilke Carlo Rissman Robert Slawek Jaroslaw Sitek Emilia Johannsen Peter Nielsen Jørgen Ren Yingxue van Blitterswijk Marka DeJesus-Hernandez Mariely Christopher Elizabeth Murray Melissa Bieniek Kevin Evers Bret Ferrari Camilla Rollinson Sara Richardson Anna Scarpini Elio Fumagalli Giorgio Padovani Alessandro Hardy John Momeni Parastoo Ferrari Raffaele Frangipane Francesca Maletta Raffaele Anfossi Maria Gallo Maura Petrucelli Leonard Suh EunRan Lopez Oscar Wong Tsz van Rooij Jeroen G Seelaar Harro Mead Simon Caselli Richard Reiman Eric Noel Sabbagh Marwan Kjolby Mads Nykjaer Anders Karydas Anna Boxer Adam Grinberg Lea Grafman Jordan Spina Salvatore Oblak Adrian Mesulam M-Marsel Weintraub Sandra Geula Changiz Hodges John Piguet Olivier Brooks William Irwin David Trojanowski John Lee Edward Josephs Keith Parisi Joseph Ertekin-Taner Nilüfer Knopman David Nacmias Benedetta Piaceri Irene Bagnoli Silvia Sorbi Sandro Gearing Marla Glass Jonathan Beach Thomas Black Sandra Masellis Mario Rogaeva Ekaterina Vonsattel Jean-Paul Honig Lawrence Kofler Julia Bruni Amalia Snowden Julie Mann David Pickering-Brown Stuart Diehl-Schmid Janine Winkelmann Juliane Galimberti Daniela Graff Caroline Öijerstedt Linn Troakes Claire Al-Sarraj Safa Cruchaga Carlos Cairns Nigel Rohrer Jonathan Halliday Glenda Kwok John van Swieten John White Charles Ghetti Bernardino Murell Jill Mackenzie Ian R Hsiung Ging-Yuek Borroni Barbara Rossi Giacomina Tagliavini Fabrizio Wszolek Zbigniew Petersen Ronald Bigio Eileen Grossman Murray Van Deerlin Vivianna Seeley William Miller Bruce Graff-Radford Neill Boeve Bradley Dickson Dennis Biernacka Joanna Rademakers RosaLANCET NEUROLOGY, 17, 548-558, 2018
TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.Mackenzie Ian Nicholson Alexandra Sarkar Mohona Messing James Purice Maria Pottier Cyril Annu Kavya Baker Matt Perkerson Ralph Kurti Aishe Matchett Billie Mittag Tanja Temirov Jamshid Hsiung Ging-Yuek Krieger Charles Murray Melissa Kato Masato Fryer John Petrucelli Leonard Zinman Lorne Weintraub Sandra Mesulam Marsel Keith Julia Zivkovic Sasha Hirsch-Reinshagen Veronica Roos Raymond Züchner Stephan Graff-Radford Neill Petersen Ronald Caselli Richard Wszolek Zbigniew Finger Elizabeth Lippa Carol Lacomis David Stewart Heather Dickson Dennis Kim Hong Joo Rogaeva Ekaterina Bigio Eileen Boylan Kevin Taylor J Paul Rademakers RosaNEURON, 95, 808-816.e9, 2017
Prosaposin is a regulator of progranulin levels and oligomerization.Nicholson Alexandra Finch NiCole Almeida Marcio Perkerson Ralph van Blitterswijk Marka Wojtas Aleksandra Cenik Basar Rotondo Sergio Inskeep Venette Almasy Laura Dyer Thomas Peralta Juan Jun Goo Wood Andrew Frayling Timothy Fuchsberger Christian Fowler Sharon Teslovich Tanya Manning Alisa Kumar Satish Curran Joanne Lehman Donna Abecasis Goncalo Duggirala Ravindranath Pottier Cyril Zahir Haaris Crook Julia Karydas Anna Mitic Laura Sun Ying Dickson Dennis Bu Guojun Herz Joachim Yu Gang Miller Bruce Ferguson Shawn Petersen Ronald Graff-Radford Neill Blangero John Rademakers RosaNature Communications, 7, 11992, 2016
Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.Rademakers Rosa Baker Matt Nicholson Alexandra Rutherford Nicola Finch NiCole Soto-Ortolaza Alexandra Lash Jennifer Wider Christian Wojtas Aleksandra DeJesus-Hernandez Mariely Adamson Jennifer Kouri Naomi Sundal Christina Shuster Elizabeth Aasly Jan MacKenzie James Roeber Sigrun Kretzschmar Hans Boeve Bradley Knopman David Petersen Ronald Cairns Nigel Ghetti Bernardino Spina Salvatore Garbern James Tselis Alexandros Uitti Ryan Das Pritam Van Gerpen Jay Meschia James Levy Shawn Broderick Daniel Graff-Radford Neill Ross Owen Miller Bradley Swerdlow Russell Dickson Dennis Wszolek ZbigniewNATURE GENETICS, 44, 200-5, 2011
Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS.DeJesus-Hernandez Mariely Mackenzie Ian Boeve Bradley Boxer Adam Baker Matt Rutherford Nicola Nicholson Alexandra Finch NiCole Flynn Heather Adamson Jennifer Kouri Naomi Wojtas Aleksandra Sengdy Pheth Hsiung Ging-Yuek Karydas Anna Seeley William Josephs Keith Coppola Giovanni Geschwind Daniel Wszolek Zbigniew Feldman Howard Knopman David Petersen Ronald Miller Bruce Dickson Dennis Boylan Kevin Graff-Radford Neill Rademakers RosaNEURON, 72, 245-56, 2011

Job openings

News

Meet Rosa Rademakers: new director of the VIB-UAntwerp Center for Molecular Neurology

24/06/2019 - Since Christine Van Broeckhoven will be retiring as director of the VIB-UAntwerp Center for Molecular Neurology, we needed someone to replace her. VIB managed to attract Rosa Rademakers, an alumnus of the center and former student of Christine.

Rosa Rademakers

Rosa Rademakers

Research area(s)

Model organism(s)

Bio

PhD: University of Antwerp, Belgium, 2004
Postdoc: University of Antwerp, Belgium 2004-2005
Postdoc: Mayo Clinic, Jacksonville, Florida, USA 2005-2007
Professor and Group Leader: Mayo Clinic, Jacksonville, Florida USA 2007-2019
Professor: University of Antwerp, Belgium since 2019
Group Leader VIB since 2019
VIB science Director since 2019

Contact Info

VIB-UAntwerp Center for Molecular NeurologyGebouw VCampus Drie EikenUniversiteitsplein 1 2610 ANTWERPENRoute description