Prof. Dr. Andreas Neueder
THE RESEARCH
Discover our research projects and learn about the methods we use. See our publications and funding bodies.
The team
current and former lab members
Christoph Janiesch (Technical assistant)
Julia Natan (MSc, 2022)
Mirjam Skobowsky (BSc, 2022)
Leonard Saitta (Dr. med., 2021)
Ronja Wagner (BSc, 2021)
Alshaimaa Abdelmoez (postdoc, 2019 - 2024)
Franziska Hoschek (Dr. rer. nat., 2019 - 2023)Nousheen Iram-Muehlinghaus (postdoc, 2020 - 2021)
Judith Rammoser (Dr. med., 2019 - 2020)
Julia Hummel (Dr. med., 2019 - 2020)
Philipp Nitzschner (Dr. med., 2019 - 2020)
Franziska Hoschek (MSc, 2019)
Nathalie Birth (Technical assistant)
Open positions
If you are intersted in our work and would like to be part of the team, please contact us.
The research
Huntington's Disease (HD)
(A) The CAG repeat expansion mutation in HTT leads to a polyQ tract in the HTT protein. (B) HD manifests with a triade of motor (chorea), cognitive and psychiatric symptoms.
Background
Huntington disease (HD) was first described in 1872 by George Huntington and is a late-onset, autosomal dominant, inherited neurodegenerative disorder. It is caused by a CAG repeat expansion mutation in exon 1 of the HTT gene resulting in an expanded polyglutamine (polyQ) tract in the huntingtin protein.
Read more here
Read more here
Molecular Changes
The expanded polyQ tract of mutated HTT results in toxic gains-of-function of the protein, the generation of small fragments of HTT, the appearance of aggregates and disruption of various cellular processes. Eventually these events lead to cell death, most prominent in the neurons of the striatum.
Read more here
HTT1a
We have previously identified a novel mechanism that leads to the generation of the most toxic fragment of HTT: exon 1 HTT. This fragment consists only of exon 1 of the HTT gene including the polyQ tract. The generation of this fragment is based on a block in the correct splicing reaction of exon 1 HTT to exon 2 HTT resulting in the generation of a novel small RNA HTT1a. This RNA based pathogenic process occurs in all knock-in mouse models of HD, and most importantly also in human HD patients.
Read the publications here
The Projects
We use a combination of molecular biology and systems biology approaches to unravel mechanisms driving HD pathogenesis.
Generation of novel models
We design, establish and analyse new models for certain aspects of pathogenetic mechanisms in HD.
'omics
We generate and analyse 'big data' in the context of HD. These datasets come from various biological sources and we use state-of-the-art technologies and bioinformatics to evaluate and integrate the 'omics datasets.
RNA biology
We are interested in the contribution of RNA-based mechanisms to cell (type specific) toxicity in HD. In particular we try to unravel mechanisms that contribute to the incomplete splicing of the HTT mRNA.
Extracellular Vesicles
EV biology is disturbed in HD. Our findings offer new insights into HD biology and molecular mechanisms contributing to disease progression, as well as the use of EVs as attractive biomarkers in the context of clinical trials.
Collaborations
Funding bodies
EHDN
European HD Network
DFG
German Research Foundation
DHH
Deutsche Huntington-Hilfe e.V.
CHDI
CHDI Foundation
MRC
Medical Research Council
contact
lab NEWS
News - 2024
BIG News!
We have moved to Hamburg at the Center for Molecular Neurobiology (ZMNH).
Exciting future research awaits!
Exciting future research awaits!
Come and visit us here or contact us if want further information.
Extracellular Vesciles in HD
In the present study, we demonstrate that examining extracellular vesicles (EVs) can give new insights into pathologic mechanisms in Huntington disease.EVs from HD individuals convey specific actionable information in comparison to EVs from healthy people highlighting the biological relevance and potential use of EVs as a biomarker in clinical trials.
https://doi.org/10.1002/ctm2.1525
Pathogenic mt-DNA mutations accumulate in HD
We show that life-long expression of mutant HTT causes a mitochondrial phenotype indicative of mtDNA instability in fresh post-mitotic human skeletal muscle. Thus, genomic instability may not be limited to nuclear DNA.
https://doi.org/10.1093/brain/awae007
News - 2023
Astrocytes in HD
Astrocytes are dysfunctional in HD patients and the alterations are driven by polyQ length-dependent metabolic alterations.
https://doi.org/10.1016/j.pneurobio.2023.102448
News - 2022
MTM-HD
The MTM-HD study, a multi-omics analysis of HD patient peripheral tissues has been accepted by Genome Biology! We show abnormal molecular signatures of inflammation, energy metabolism and vesicle biology.
https://doi.org/10.1186/s13059-022-02752-5
TGFβ signaling in the Retina
TGFβ signaling in retinal neurons and Müller cells exhibits a neuroprotective effect and might pose promising therapeutic options to attenuate photoreceptor degeneration in humans.
https://doi.org/10.3390/ijms23052626
MTM-HD preprint
Read our pre-print about the MTM-HD study, a multi-omics analysis of HD patient peripheral tissues. We show abnormal molecular signatures of inflammation, energy metabolism and vesicle biology.
https://doi.org/10.1101/2022.02.03.475821
News - 2021
The nucleolus in HD
The integrity of the nucleolus is an important contributor to the formation of HTT aggregates. Monitoring this could prove to be a biomarker for HD progression.
https://doi.org/10.1038/s41419-021-04432-x
Tau in ALS
Read how targeting the Tau protein might have therapeutic potential in ALS (Amyotrophic Lateral Sclerosis)
https://doi.org/10.1007/s12035-021-02557-w
Retinitis pigmentosa
We have analysed the transcriptional changes in a model for retinits pigmentosa, a neurodegenerative disease of the retina.
https://doi.org/10.3390/ijms22126307
Habilitation
Dr. Neueder successfully finished his Habilitation in the field of experimental neurology at Ulm University.
News - 2020
SRSF6 and Splicing
Our paper about the role of SRSF6 in the splicing events of HTT just got published.
https://doi.org/10.1038/s41598-020-71111-w
Mitochondria in HD
Read our review about mitochondrial biology in HD.
https://doi.org/10.2217/nmt-2019-0033
BW-HDZ teaching certificate
Dr. Neueder successfully finished his BW-HDZ 'Baden-Württemberg-Zertifikat für Hochschuldidaktik'.
Read about it here.
News - 2019
Junior faculty
Dr. Neueder became a member of the International Graduate School in Molecular Medicine Ulm (IGradU) junior faculty.
Read about it here.
Paper got Published
Our paper showing that phenotype onset in Huntington’s disease knock-in mice is correlated with the incomplete splicing of the mutant huntingtin gene is published in the Journal of Neuroscience Research. Read it here: https://doi.org/10.1002/jnr.24493
Review got Published
A new review about RNA-Mediated Disease Mechanisms in Neurodegenerative Disorders is published and accessible from here:
https://doi.org/10.1016/j.jmb.2018.12.012
News - 2018
Paper got accepted!
Our new paper about mechanisms that contribute to HTT mis-splicing got accepted by Nature Communications!
Accessible from here:
https://doi.org/10.1038/s41467-018-06281-3
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