Taming widespread collateral damage of CRISPR editing
May 2020
CRISPR-Cas9 has revolutionized disease-research, as it greatly simplifies targeted genome editing. However, CRISPR systems are not entirely accurate and can introduce potentially harmful additional mutations, called on-target effects. In a collaborative study with the DichgansLab, the PaquetLab identified widespread prevalence of on-target effects in clinically relevant CRISPR-edited iPS cells and describes broadly applicable tools to detect these unintended alterations. The new method improves the reliability of CRISPR editing.
Machine learning analysis of whole mouse brain vasculature
March 2020
The Ertürk lab in collaboration with others (ISD, Helmholtz Munich and TUM) developed an artifical intelligence aided tool to study the vasculature in complete transparent mouse brains. Using 3D microscopy, they visualized the underlying complex network of all brain vessels at the capillary level. Their new tool can generate reference maps of the adult mouse brain vasculature, which could be used to model synthetic cerebrovascular networks. On this basis, unknown vascular properties can be discovered and biological models can be confirmed...
Aβ deposition associated with white matter alterations in cognitive normal people
In an international collaboration, ISD researchers report increased amyloid PET uptake to be associated with higher age-related fiber tract alterations and white matter hyperintensities in cognitively asymptomatic people...
February 2020
The Ertürk lab (ISD and Helmholtz Munich) managed to make intact human organs transparent. Using microscopic imaging they visualized underlying complex structures of see-through organs at the cellular level. Resulting organ maps could serve as templates for 3D-bioprinting technologies. This eventually could contribute to the creation of on demand artificial organs for patients in need...
Digital medicine model of cognitive worsening in Alzheimer’s disease
In a large collaborative study with the North American DIAN and ADNI studies, ISD researchers developed a fully automated and cross-validated machine-learning algorithm for the prediction of disease progression in Alzheimer’s disease. The biofluid and neuroimaging derived model allows to predict the rate of cognitive decline over a clinically relevant time window of 4 years….
January 2020
Using Mendelian Randomization ISD investigators showed that genetic predisposition to higher HDL-C, specifically to cholesterol in medium-sized HDL, is associated with small vessel stroke and white matter injury. Their analyses indicate that HDL-C-raising strategies could be considered for the prevention of ischemic small vessel disease but the net benefit of such an approach needs to be tested in a randomized controlled trial...
Tau spreading associated with functional connectivity in Alzheimer’s disease
A multinational study led by the Ewers Lab and first author Nicolai Franzmeier shows that functional brain architecture predicts the spatial patterns of the gradual spreading of tau pathology in Alzheimer's disease, supporting in-vitro findings of trans-neuronal tau propagation...
December 2019
ISD researchers developed a metaGRS for ischaemic stroke (IS) that outperforms previous GRS and identifies a subset of individuals at monogenic levels of risk. Individuals in the top 0.25% of the metaGRS have a threefold increased risk of IS. The results suggest that, for individuals with a high metaGRS, achieving risk factor levels recommended by current guidelines may be insufficient to mitigate risk...
Combining clearing technology with deep learning algorithms ISD investigators developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting (DeepMACT) that enables analysing the size, shape, and spatial distribution of metastases, and the degree to which metastases are targeted by therapeutic monoclonal antibodies in entire mice...
Ali Ertürk received a prestigious ERC Consolidator Grant for his research project CALVARIA ‘Translational Aspects of the Discovery of Skull-Meninges Connections’. SMCs where recently discovered by Ali Ertürk and others and enable immune cells to migrate into the brain suggesting they could play a role in brain disorders including stroke and dementia ...
Hertie Network of Excellence in Clinical Neuroscience
November 2019
Neuroscientists at LMU and TUM have been awarded members of the Hertie Network of Excellence in Clinical Neuroscience. The program provides support of junior scientists and facilitates collaborations across participating sites. The scientific focus of the Munich site (Speakers: M. Dichgans and Thomas Korn) is on neurovascular, neurodegenerative, and neuroinflammatory diseases and underlying mechanisms...
Medical Excellence fellowship for ISD Researcher
Philip Melton, MD student in the Liesz lab, was awarded the „Medical Excellence“ Fellowship 2019 in the field of Neuroscience for „StrokeMicroBiomics“. The project explores long-term microbiome dysbiosis and metabolomic changes in stroke patients...
Circulating MCP-1 levels associate with stroke risk
September 2019
Expanding on their previous Mendelian Randomisation study (CIRCULATION 2019) ISD researchers now provide further evidence for a causal role of MCP-1 in stroke. In a meta-analysis of observational data from 17,180 stroke-free individuals they found higher circulating MCP-1 levels to be associated with long-term risk of incident ischemic stroke...
Protective effects of TREM2 in Alzheimer's Disease
August 2019
The teams of M. Ewers and C. Haass found higher cerebrospinal fluid comcentrations of TREM2, a biomarker of microglia activation, to slow down cognitive decline in Alzheimer's Disaease...
Novel insights into small vessel disease progression
July 2019
Using a prospective, high-frequency serial imaging study, a team of researchers at ISD and Radboudumc Nijmegen identified acute infarcts as the cause of incident lacunes and almost a third of incident microbleeds. In contrast, the progression of white matter hyperintensities was independent from acute infarcts. These new insights were enabled through a unique study design with monthly MRI exams...
ISD Research Retreat
July 10th and 11th ISD research teams met for the yearly scientific retreat to present their projects and discuss the science. At the heart of this meeting were presentations from all Ph.D. students, including an evning poster session. The last year brought about important achievements both scientifically and with regard to expertise and infrastructure. The meeting further served as an opportunity to familiarize people with the medium- and long-term strategy of ISD...
The project led by Christian Grimm (Walther‐Straub‐Institute) and Dominik Paquet (ISD) is supported with 86.000 Euros by the German Neuronal Ceroid Lipofuscinosis Foundation (NCL) and aims to develop novel treatment strategies for childhood dementia...
April 2019
A multinational study led by Michael Ewers and his team suggests that enhanced tau pathology may underlie the increased risk of Alzheimer’s conferred by the BIN1 single nucleotide polymorphism - the second most important genetic risk factor of AD...
ISD researchers found a common variant in the BDNF gene to modulate the impact of amyloid pathology on hippocampal network connectivity and memory in Alzheimer’s disease...
March 2019
Congratulations to our longstanding collaborators Marie-Germain Bousser, Anne Joutel, Hugues Chabriat, & Elisabeth Tournier-Lasserve (Paris, Fr.) for receiving the prestigious BRAIN price. Their groundbreaking work on CADASIL has profoundly influenced the understanding of cerebral small vessel disease & vascular cognitive impairment...
February 2019
A combined fMRI and tau PET study in Alzheimer’s disease by Michael Ewers and team shows that the spatial pattern of tau pathology is predicted by functional network connectivity, suggesting that cross-talk between brain regions is conducive to tau spreading...
January 2019
The Erturk group developed a nanobody-based immunolabeling method, vDISCO, that enables imaging subcellular details in transparent mice. They uncovered neuronal projections and skull–meninges connections in whole adult mice that are likely to have relevance in both health and disease...
November 2018
Ali Ertürk has been awarded $715.000 from NIH (USA) to explore the role of brain lymphatic/glymphatic systems in dementia and ageing in collaboration with Maiken Nedergaard (Rochester University, New York)...
A genome-wide meta-analysis involving almost 900.00 subjects from the MEGASTROKE consortium and UK Biobank identified new risk loci for stroke among them endothelial nitric oxide synthase (NOS3). The study further suggests that genetic variation in the NOS - nitric oxide (NO) pathway in part affects stroke risk via variation in blood pressure...
October 2018
ISD investigators in collaboration with researchers from France found that MoCA, a brief cognitive test, when taken within a week after stroke predicts the risk of cognitive impairment, functional impairment and mortality up to 3 years later. The findings inform clinical practice by highlighting the need of early cognitive screening after stroke...
September 2018
Using a Mendelian Randomization approach and data from >800.000 individuals ISD investigators showed that genetic predisposition to higher levels of the inflammatory cytokine MCP-1 is associated with a higher risk of stroke, in particular large artery stroke and cardioembolic stroke. These findings inform the planning of future clinical trials...
The first funding decisions in the context of the Excellence Strategy have been announced. Four Clusters of Excellence including the Munich Cluster for Systems Neurology (SyNergy) submitted by LMU and TUM were successful and will receive funding from 2019 on...
Ewers and his team found the evolution of white matter alterations to start in callosal fibers already 10 years before estimated symptoms onset in familial Alzheimer’s disease...
August 2018
Chenchen Pan from Ali Ertuerk's group received the Chinese government award for outstanding self-finance students abroad. Established by the China Scholarship Council in 2003 the award is considered the highest recognition given by the Chinese government to graduate students abroad who do not receive financial support from the Chinese government...
July 2018
A prestigious ERC Starting Grant was awarded to the ISD researcher Arthur Liesz for the project „RecoverInFlame“. The 1.5M € award by the European Research Council (ERC) will support the Liesz lab to investigate inflammatory mechanisms in the recovery after acute stroke...
Stefan Roth and Dr. Arthur Liesz were awarded with the "Rolf-Becker"-Prize for one of the best scientific outputs in 2017/18 by the Medical Faculty of LMU Munich and the foundation "Rufzeichen Gesundheit!" Baierbrunn. They received this prestigious award for their recent work published in Science Translational Medicine...
May 2018
A large scale genetic study on major brain diseases including stroke and Alzheimer's disease revealed shared genetic influences between multiple brain disorders and relevant phenotypes, including cognitive measures. The results highlight the value of heritability-based methods in understanding the ethiology of neurological and psychiatric disorders. ISD investigators were on the steering committee of this work which was published in Science...
The Collaborative Research Center SFB1123 „Atherosclerosis – Mechanisms and Networks of Novel Therapeutic Targets" has been approved a second funding period. The ISD contributes to the LMU led network with two projects, headed by Martin Dichgans/Yaw Asare (project B5) and Jürgen Bernhagen (project A3), as well as flanking project C1 (Arthur Liesz)...
Steffen Tiedt, a clinician scientist at the ISD has been awarded the Young Investigator Award 2018 by the European Stroke Organisation (ESO) for his work on serum Neurofilament Light as a marker for neuroaxonal injury after stroke...
Complex heart surgery may lead to organ dysfunction such as acute kidney injury (AKI) or ischemic stroke. A researcher team led by Aachen University and the Bernhagen lab found that patients with high blood levels of the cytokine MIF had a reduced risk of developing AKI. The study is published in this week’s issue of Sci Transl Med...
Isolation of CADASIL patient brain vessels in combination with proteome analysis identified loss of HTRA1 proteolytic function as a critical step in the development of disease pathology providing novel insights into the molecular mechanisms of cerebral small vessel diseases....
Apr 2018
The Bernhagen lab at ISD together with collaborating labs uncovered a previously unrecognized connection between the atherogenic chemokine-like cytokine MIF and B cell function in atherosclerosis...
Mar 2018
Munich, March 21-23, the European Stroke Organisation (ESO) in collaboration with the Stroke Alliance for Europe (SAFE) convened leading experts in stroke research and care to an international workshop targeted at identifying current challenges in the prevention and treatment of stroke, set the goals for the next decade...
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