A5063441147- Viral-associated cancers and disorders
- RNA modifications and cancer
- Cytomegalovirus and herpesvirus research
- Alzheimer's disease research and treatments
- RNA Research and Splicing
- Parvovirus B19 Infection Studies
- Microtubule and mitosis dynamics
- Immune Cell Function and Interaction
- Neuroinflammation and Neurodegeneration Mechanisms
- Lymphoma Diagnosis and Treatment
- CAR-T cell therapy research
- RNA and protein synthesis mechanisms
- Inflammation biomarkers and pathways
- Cancer Genomics and Diagnostics
- Amyotrophic Lateral Sclerosis Research
- Histiocytic Disorders and Treatments
- Epigenetics and DNA Methylation
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Herpesvirus Infections and Treatments
- Cholinesterase and Neurodegenerative Diseases
- Genomics and Chromatin Dynamics
- Polyomavirus and related diseases
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
Center for Environmental Health
2018-2025
Helmholtz Zentrum München
2016-2025
German Center for Neurodegenerative Diseases
2016-2025
Munich Cluster for Systems Neurology
2016-2025
Helmholtz-Institute Münster
2024
Ludwig-Maximilians-Universität München
1996-2022
German Center for Diabetes Research
2017-2022
Heinrich Heine University Düsseldorf
2022
Deutsches Diabetes-Zentrum e.V.
2022
Heidelberg University
2008-2017
Ferroptosis, a non-apoptotic form of cell death marked by iron-dependent lipid peroxidation1, has key role in organ injury, degenerative disease and vulnerability therapy-resistant cancers2. Although substantial progress been made understanding the molecular processes relevant to ferroptosis, additional cell-extrinsic cell-intrinsic that determine sensitivity toward ferroptosis remain unknown. Here we show fully reduced forms vitamin K-a group naphthoquinones includes menaquinone...
N 6 -methyladenine (m A) is found on many eukaryotic RNAs including mRNAs. m A modification has been implicated in mRNA stability and turnover, localization, or translation efficiency. heterodimeric enzyme complex composed of METTL3 METTL14 generates METTL3/14 the nucleus where it localized to nuclear speckles splicing regulator WTAP required for this distinct localization pattern. Although recent crystal structures revealed how catalytic MT-A70 domains interact with each other, a more...
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus linked to number of B cell cancers and lymphoproliferative disorders. During latent infection, EBV expresses 25 viral pre-microRNAs (miRNAs) induces the expression specific host miRNAs, such as miR-155 miR-21, which potentially play role in oncogenesis. To date, only limited miRNA targets have been identified; thus, miRNAs pathogenesis and/or lymphomagenesis not well defined. Here, we used photoactivatable ribonucleoside-enhanced...
Primary infection with the human oncogenic Epstein-Barr virus (EBV) can result in infectious mononucleosis (IM), a self-limiting disease caused by massive lymphocyte expansion that predisposes for development of distinct EBV-associated lymphomas. Why some individuals experience this symptomatic primary EBV infection, whereas majority acquires asymptomatically, remains unclear. Using mouse model reconstituted immune system components, we show depletion natural killer (NK) cells enhances IM...
Article10 March 2020Open Access Enhancing protective microglial activities with a dual function TREM2 antibody to the stalk region Kai Schlepckow German Center for Neurodegenerative Diseases (DZNE) Munich, Germany Search more papers by this author Kathryn M Monroe Denali Therapeutics Inc., South San Francisco, CA, USA Gernot Kleinberger orcid.org/0000-0002-5811-8226 Metabolic Biochemistry, Biomedical (BMC), Faculty of Medicine, Ludwig-Maximilians-Universität München, Ludovico...
Report30 August 2017Open Access Source DataTransparent process An Alzheimer-associated TREM2 variant occurs at the ADAM cleavage site and affects shedding phagocytic function Kai Schlepckow Biomedical Center (BMC), Biochemistry, Ludwig-Maximilians-Universität München, Munich, Germany Search for more papers by this author Gernot Kleinberger orcid.org/0000-0002-5811-8226 Munich Cluster Systems Neurology (SyNergy), Akio Fukumori German Neurodegenerative Diseases (DZNE) Regina Feederle Helmholtz...
Therapeutic modulation of TREM2-dependent microglial function might provide an additional strategy to slow the progression Alzheimer's disease. Although studies in animal models suggest that TREM2 is protective against pathology, its effect on tau pathology and potential beneficial role people with disease still unclear. Our aim was study associations between dynamics soluble TREM2, as a biomarker signalling, amyloid β (Aβ) deposition, tau-related neuroimaging markers, cognitive decline,...
The Epstein–Barr virus (EBV) nuclear antigen 1 (EBNA1) is one of the earliest viral proteins expressed after infection and only latent protein consistently in viral-associated tumors. EBNA1's crucial role DNA replication, episomal maintenance, partitioning well examined whereas its importance for immortalization process tumorgenicity EBV unclear. To address these open questions, we generated, based on maxi-EBV system, an EBNA1-deficient mutant used this strain to infect primary human B...
The Epstein-Barr virus (EBV) is found in a variety of tumors whose incidence greatly varies around the world. A poorly explored hypothesis that particular EBV strains account for this phenomenon. We report M81, isolated from Chinese patient with nasopharyngeal carcinoma (NPC), shows remarkable similarity to other NPC viruses but divergent all known strains. M81 exhibited reversed tropism relative common reduced ability infect B cells and high propensity epithelial cells, which agreement its...
Abstract Immunotherapeutic approaches are currently the most advanced treatments for Alzheimer's disease ( AD ). Antibodies against amyloid β‐peptide (Aβ) bind to plaques and induce their clearance by microglia via Fc receptor‐mediated phagocytosis. Dysfunctions of may play a pivotal role in pathogenesis could result reduced efficacy antibody‐mediated Aβ clearance. Recently, heterozygous mutations triggering receptor expressed on myeloid cells 2 TREM ), microglial gene involved phagocytosis,...
Epstein-Barr virus (EBV), an oncogenic human herpesvirus, induces cell proliferation after infection of resting B lymphocytes, its reservoir in vivo. The viral latent proteins are necessary for permanent growth, but it is unknown whether they sufficient. EBV was recently found to encode microRNAs (miRNAs) that expressed infected cells and some EBV-associated lymphomas. miRNAs grouped into two clusters located either adjacent the BHRF1 gene or introns contained within BART transcripts. To...
The C9orf72 GGGGCC repeat expansion is a major cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). Non-conventional translation results in five dipeptide proteins (DPRs), but their clinical utility, overall significance, temporal course the pathogenesis c9ALS/FTD are unclear, although animal models support gain-of-function mechanism. Here, we established poly-GP immunoassay from cerebrospinal fluid (CSF) to identify characterize patients. Significant levels were...
The protease BACE1 (beta-site APP cleaving enzyme) is a major drug target in Alzheimer's disease. However, therapeutic inhibition may cause unwanted adverse effects due to its additional functions the nervous system, such as myelination and neuronal connectivity. Additionally, recent proteomic studies investigating cell lines cultured murine neurons identified wider range of membrane proteins potential substrates, including seizure protein 6 (SEZ6) homolog SEZ6L. We generated antibodies...
Hexanucleotide repeat expansion in C9orf72 is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis, but pathogenic mechanism this mutation remains unresolved. Haploinsufficiency has been proposed as one potential mechanism. However, insights if how reduced proteins levels might contribute to disease pathogenesis are still limited because expression, localization functions central nervous system (CNS) uncertain, part due poor specificity currently...
Abstract Trans-activation response DNA-binding protein of 43 kDa (TDP-43) regulates RNA processing and forms neuropathological aggregates in patients with amyotrophic lateral sclerosis frontotemporal lobar degeneration. Investigating TDP-43 post-translational modifications, we discovered that K84 acetylation reduced nuclear import whereas K136 impaired binding splicing capabilities TDP-43. Such failure interaction triggered phase separation mediated by the C-terminal low complexity domain,...
Abstract Aggregates of medin amyloid (a fragment the protein MFG-E8, also known as lactadherin) are found in vasculature almost all humans over 50 years age 1,2 , making it most common currently known. We recently reported that aggregates blood vessels ageing wild-type mice, causing cerebrovascular dysfunction 3 . Here we demonstrate amyloid-β precursor (APP) transgenic mice and patients with Alzheimer’s disease co-localizes vascular deposits, deficiency reduces deposition by half. Moreover,...
Ferroptosis is an iron-dependent form of cell death driven by biochemical processes that promote oxidation within the lipid compartment. Calcium (Ca2+) a signaling molecule in diverse cellular such as migration, neurotransmission, and death. Here, we uncover crucial link between ferroptosis Ca2+ through identification novel tetraspanin MS4A15. MS4A15 localizes to endoplasmic reticulum, where it blocks depleting luminal stores reprogramming membrane phospholipids ferroptosis-resistant...
The centrosome provides an intracellular anchor for the cytoskeleton, regulating cell division, migration, and cilia formation. We used spatial proteomics to elucidate protein interaction networks at of human induced pluripotent stem cell-derived neural cells (NSCs) neurons. Centrosome-associated proteins were largely type-specific, with hubs involved in RNA dynamics. Analysis neurodevelopmental disease cohorts identified a significant overrepresentation NSC variants patients periventricular...