GENOMIC TECHNOLOGIES AND IMMUNO-GENOMICS
Our Research
Our research group focuses on the application of the latest genomic technologies to understand human disease. A particular emphasis is put on the understanding of genetic defects that explain immune diseases, specifically in primary immunodeficiencies (PIDs) and inborn errors of immunity (IEIs).
The immuno-genomics group combines expertise in both genomics and immunology. This research group is affiliated with the Department of Human Genetics and the Department of the Internal Medicine of the RadboudUMC in Nijmegen, as well as the RIMLS.
TEAM
ALEXANDER HOISCHEN, PHD
Group leader, PI, Associate Professor
Alex studied biology in Bonn, Germany, where he also received his PhD in human genetics. Since 2007 Alex works at the Radboud University Medical Center, Nijmegen, The Netherlands; and since 2013 he leads this research group.
Alex has a passion for latest genomic technologies, that allow insights into (rare) diseases.
TUOMO MANTERE, PHD
Postdoc
Tuomo obtained his PhD in 2017 from the University of Oulu (Finland). Projects were mainly related to the identification of novel breast cancer predisposition genes with next-generation sequencing approaches. Shortly after PhD, Tuomo did a two-years post-doc in the Lab of Dr. Alexander Hoischen in Nijmegen (the Netherlands). Here he was involved in projects utilizing novel genomic technologies to unravel rare diseases, mainly focusing on proof-of-concept studies utilizing optical genome mapping. Now back in Finland since June 2020, and recently obtained funding from the Academy of Finland, I have launched new research projects where optical genome mapping is also an important tool (mainly hereditary breast cancer and also other, e.g. rare diseases and leukemia). Tuomo keeps a guest scientist position in this research group.
ROSANNE VAN DEUREN
Former PhD candidate
Rosanne studied biomedical sciences and received a MSc in Genetic Epidemiology. She worked on her PhD project entitled: Impact of common, rare and somatic variants on innate immune responses in health and disease
CAS VAN DER MADE, MD
PhD candidate
Cas studied medicine, and works on his PhD project entitled: Functional genomics of primary immunodeficiencies – towards personalized medicine in PIDs
EMIL VORSTEVELD, MSC
PhD candidate
Emil studied medical biology, and now works on his PhD project entitled: Solving the Unsolved – Integrated DNA and RNA Analysis to Unravel the Causes of Primary Immunodeficiencies.
MARLOES STEEHOUWER, BSC
Research Technician
Marloes is a member of this research group since its beginning. Marloes is an expert in latest genomic technologies, including a great variety of sequencing techniques.
SIMON VAN REIJMERSDAL, BSC
Research Technician
Simon is an expert in DNA and RNA sequencing approaches.
ANNE HEBERT
Master student
Anne studies molecular mechanisms of disease, and performs a half year internship in our group.
WOUTER STEYAERT
PhD candidate (co-supervised with C. Gilissen
Wouter does his PhD as part of the SOLVE-RD project (www.solve-rd.eu), and is co-supervised by C. Gilissen.
BART VAN DER SANDEN
PhD candidate (co-supervised with L. Vissers)
Bart performs his PhD project entitled:
Clinical genome interpretation: beyond the coding sequence.
is co-supervised by L. Vissers.
CHARLOTTE KAFFA, BSC
Bioinformatician
Charlotte is a bioinformatician in PB t'Hoen's research team.
FORMER GROUP MEMBERS
PEER ARTS, PHD
PhD candidate 2012-2017, now postdoc Adelaide
Peer has always been intrigued by implementation of novel technologies and methodologies with a goal to better understand the molecular mechanisms of human diseases. During his PhD at the department of human genetics of Radboud University Medical Center in Nijmegen (The Netherlands) he applied innovative technologies in the fields of genetics and immunology to show how genetic mutations can lead to different (immunological and developmental) disorders. In patient-focused research projects he has shown that disease gene identification is important for the diagnosis and clinical management of human (immunological) diseases.
After finishing his PhD in 2017, Peer became a post-doctoral fellow in the research team of Professor Hamish Scott at the Centre for Cancer Biology (CCB) and the University of South Australia (UniSA). Within this research group they currently apply multi-omics tools (genomics, transcriptomics) to understand the pathogenesis of different diseases (ranging from early (perinatal lethality to predisposition to haematological malignancies).
ROCÍO ACUÑA HIDALGO, MD, PHD
PhD candidate 2013-2017, now CSO Nostos Genomics
Rocío is a medical doctor who received her PhD entitled 'Timing of de novo mutations - relevance to health and disease' in our group in 2017. Rocío has carried out award-winning research in ourprestigious institutions such as the Max Planck Institute and the University of Washington, mastering new technologies including CRISPR and NGS.
She is the co-founder and CSO of Nostos Genomics.
WYBRICH CNOSSEN, MD, PHD
Former PhD student (co-supervised with Prof Dr Joost Drenth and Prof Dr Joris A Veltman)
Wybrich received her PhD in 2017.
CLARA SERRA JUHÉ; PHD
Dr Clara Serra Juhé; former PhD student and visiting scientist. University Popeu Fabra, Barcelona, Spain
As part of her PhD Clara worked in our group 2011-2012.
Our group has hosted many visiting scientists and students over the years:
Aina Marsal Olivan (visiting scientist 2022); St. Pau hospital, Barcelona
Emil Vorsteveld (master student 2020)
Laura Batlle Maso (visiting scientist 2018); Hospital Vall d'Hebron, Barcelona
Dr Gael Nicolas (visiting scientist 2016/2017); current affiliation: Department of Genetics and CNR-MAJ Normandie Univ, UNIROUEN, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine, France
- Hilal Sengül (master student 2016/2017)
Elanur Yilmaz (visiting scientist 2016)
Nehir Kurtas (master student 2015/2016)
Tan Bo (visiting scientist 2014); State Key Laboratory of Medical Genetics, Central South University
Dr Kerstin Ludwig (visiting scientist 2015); University Bonn, Institute of Human Genetics, Department of Genomics
Dr Benjamin Rodriguez-Santiagio (visiting scientist 2011/2012); St Pau Hospital, Barcelona
LATEST NEWS AND HIGHLIGHTS
TLR7 DEFICIENCY PREDISPOSES TO SEVERE COVID-19 IN MEN
In this case series of 4 young male patients with severe COVID-19, rare putative loss-of-function variants of X-chromosomal TLR7 were identified that were associated with impaired type I and II IFN responses. These preliminary findings provide insights into the pathogenesis of COVID-19.
SCREEN FOR MORE TLR7 MUTATIONS
Spanish-Dutch research has revealed two new mutations in the TLR7 gene in healthy young men who became seriously ill with severe Covid-19. It’s becoming increasingly plausible that such mutations undermine a sufficient immune response against SARS-CoV-2
IN THE NEWS
Somatic mutations:
Mosaic mutations may not be rare - The Scientist
Timing of new mutations - Radboudumc
Genomic technologies:
Optical genome mapping comment
Optical genome mapping at ESHG2019
Radboud UMC, NimaGen Partner to Develop Targeted Sequencing Kits
Long-read sequencing Nature webinar series
COVID-19 genetics:
Presence of Genetic Variants Among Young Men With Severe COVID-19
Genetic mutation reveals how coronavirus strikes - TLR7 plays essential role in disease process
TLR7 deficiency – The Atlantic
Other/popular press:
WEBINARS & PODCASTS
PRICES & AWARDS
RIMLS research highlights 2022
Hermesdorf Prijs (Radboud University)
2011 - NCMLS award for breakthrough paper of 2011
2011 - GfH (German Society of Human Genetics) poster price "Disease Gene Identification by exome sequencing"
PHD THESES
Rosanne van Deuren - Impact of common, rare and somatic variants on innate immune responses in health and disease
Rocío Acuña Hidalgo – Timing of de novo mutations - relevance to health and disease
Peer Arts - Primary immunodeficiencies - from genetic basis to therapeutic targets
POLITICAL/STRATEGY DOCUMENTS
Political/strategy documents:
COMMITTEE ACTIVITIES
Committee Activities:
Member scientific program committee European Society of Human Genetics (ESHG) (since 2022)
Elected member scientific program committee German Society of Human Genetics (GfH) (since 2018)
Organizing Director of European Society of Human Genetics (ESHG) /European School of Genetic Medicine (ESGM) - Clinical Genomics & NGS summer school (2013, and since 2017)
Co-organizer and Faculty member of the “Genetica Retreat Rolduc” (since 2013)
Scientific Advisor for Medical Genetics and Molecular Medicine at Haukeland University Hospital, University of Bergen, Norway (2011-2013)
MOST IMPORTANT PUBLICATIONS
With first or last author contribution from our group
PREPRINTS
One Sentence Summary: In obesity, the rate of mutation-driven haematopoietic clones increased with insulin resistance and low HDL-C, both known risk factors for cardiovascular disease.
2022
Long-read technologies identify a hidden inverted duplication in a family with choroideremia
2021
Clonal hematopoiesis is associated with low CD4 nadir and increased residual HIV transcriptional activity in virally suppressed individuals with HIV; J Infect Dis. 2021 Aug 21:jiab419.
Genetic Screening for TLR7 Variants in Young and Previously Healthy Men With Severe COVID-19; Front Immunol. 2021 Jul 23;12:719115.
Next-generation cytogenetics: Comprehensive assessment of 52 hematological malignancy genomes by optical genome mapping; Am J Hum Genet. 2021 Aug 5;108(8):1423-1435.
Optical genome mapping enables constitutional chromosomal aberration detection; Am J Hum Genet. 2021 Aug 5;108(8):1409-1422.
Optical genome mapping identifies a germline retrotransposon insertion in SMARCB1 in two siblings with atypical teratoid rhabdoid tumors; J Pathol. 2021 Oct;255(2):202-211.
Adult-onset autoinflammation caused by somatic mutations in UBA1: A Dutch case series of patients with VEXAS; J Allergy Clin Immunol. 2022 Jan;149(1):432-439.e4.
Impact of rare and common genetic variation in the interleukin-1 pathway on human cytokine responses; Genome Med. 2021 May 25;13(1):94.
Genome of Peştera Muierii skull shows high diversity and low mutational load in pre-glacial Europe; Curr Biol. 2021 Jul 26;31(14):2973-2983.e9.
Next-Generation Sequencing in the Field of Primary Immunodeficiencies: Current Yield, Challenges, and Future Perspectives; Clin Rev Allergy Immunol. 2021 Oct;61(2):212-225.
Long-read trio sequencing of individuals with unsolved intellectual disability; Eur J Hum Genet. 2021 Apr;29(4):637-648.
2020
Transcriptional and functional insights into the host immune response against the emerging fungal pathogen Candida auris; Nat Microbiol. 2020 Dec;5(12):1516-1531.
Presence of Genetic Variants Among Young Men With Severe COVID-19; JAMA. 2020 Aug 18;324(7):663-673.
A Genetics-First Approach Revealed Monogenic Disorders in Patients With ARM and VACTERL Anomalies; Front Pediatr. 2020 Jun 23;8:310.
Primary immunodeficiencies in cytosolic pattern-recognition receptor pathways: Toward host-directed treatment strategies; Immunol Rev. 2020 Sep;297(1):247-272.
Rare genetic variants in interleukin-37 link this anti-inflammatory cytokine to the pathogenesis and treatment of gout; Ann Rheum Dis. 2020 Apr;79(4):536-544.
2019
Exome sequencing in routine diagnostics: a generic test for 254 patients with primary immunodeficiencies; Genome Med. 2019 Jun 17;11(1):38.
Long-Read Sequencing Emerging in Medical Genetics; Front Genet. 2019 May 7;10:426.
Somatic variants in autosomal dominant genes are a rare cause of sporadic Alzheimer's disease; Alzheimers Dement. 2018 Dec;14(12):1632-1639.
ALL PUBLICATIONS
COLLABORATORS & RESOURCES
Collaborators
INTERNATIONAL COLLABORATING LABS/GROUPS
INTERNATIONAL COLLABORATING LABS/GROUPS
Mihai Netea, Nijmegen, NL
Leo Joosten, Nijmegen, NL
Christian Gilissen, Nijmegen, NL
Lisenka Vissers, Nijmegen, NL
Han Brunner, Nijmegen, NL
Masoud Esteki Zamani, Maastricht, NL
Interested in learning more about my research?
CONTACT
Radboud University Medical Center
Department of Human Genetics (855) & Department of Internal Medicine (463)
Geert Grooteplein Zuid 10
Nijmegen, 6525 GA
Niederlande
+31 (024) 3619639