A5071117269- Monoclonal and Polyclonal Antibodies Research
- Toxin Mechanisms and Immunotoxins
- Transgenic Plants and Applications
- Cancer Research and Treatments
- HER2/EGFR in Cancer Research
- Chromatin Remodeling and Cancer
- Cell death mechanisms and regulation
- RNA Interference and Gene Delivery
- Hedgehog Signaling Pathway Studies
- CAR-T cell therapy research
- Glycosylation and Glycoproteins Research
- Radiopharmaceutical Chemistry and Applications
- Microtubule and mitosis dynamics
- Lung Cancer Treatments and Mutations
- Head and Neck Surgical Oncology
- Neuroblastoma Research and Treatments
- Cancer therapeutics and mechanisms
- Genetics and Neurodevelopmental Disorders
- Congenital heart defects research
- Genomics and Chromatin Dynamics
- Protein purification and stability
- Genomic variations and chromosomal abnormalities
- Extracellular vesicles in disease
- Protein Degradation and Inhibitors
- Cancer Treatment and Pharmacology
University Medical Center Hamburg-Eppendorf
2018-2024
Universität Hamburg
2018-2024
Kinderkrebs-Zentrum Hamburg
2018-2024
University Cancer Center Hamburg
2022
Fraunhofer Institute for Molecular Biology and Applied Ecology
2010-2020
Society of Paediatric Oncology and Haematology
2018
Fraunhofer Society
2014-2015
State University of New York
1999
Rensselaer Polytechnic Institute
1999
The interaction of CNS tumors with infiltrating lymphocytes plays an important role in their initiation and progression might be related to therapeutic responses. Gene expression-based methods have been successfully used characterize the tumor microenvironment. However, methylation data are now increasingly for molecular diagnostics there currently only few infer information about microenvironment from this type. Using approach based on differential principal component analysis, we developed...
Abstract Germline mutations in the basic helix‐loop‐helix transcription factor 4 ( TCF4 ) cause Pitt–Hopkins syndrome (PTHS), a developmental disorder with severe intellectual disability. Here, we report findings from new mouse model central nervous system‐specific truncation of Tcf4 leading to phenotypic abnormalities. Furthermore, it allows study complete knockout adult mice, circumventing early postnatal lethality previously published models. Our data suggest that results an impaired...
CREB (cyclic AMP response element binding protein) protein (CBP, CREBBP) is a ubiquitously expressed transcription coactivator with intrinsic histone acetyltransferase (KAT) activity. Germline mutations within the CBP gene are known to cause Rubinstein-Taybi syndrome (RSTS), developmental disorder characterized by intellectual disability, specific facial features and physical anomalies. Here, we investigate mechanisms of function during brain development in order elucidate morphological...
In normal epithelia, the epithelial cell adhesion molecule (EpCAM) expression is relatively low and only present at basolateral surface. contrast, EpCAM aberrantly overexpressed in various human carcinomas. Therefore, considered to be a highly promising target for antibody-based cancer immunotherapy. Here, we new fully cytolytic fusion protein (CFP), designated "anti-EpCAM(scFv)-MAP," that comprised of an EpCAM-specific antibody fragment (scFv) genetically fused microtubule-associated tau...
Abstract: Antibody–drug conjugates (ADCs) can deliver toxins to specific targets such as tumor cells. They have shown promise in preclinical/clinical development but feature stoichiometrically undefined chemical linkages, and those based on full-size antibodies achieve only limited penetration. SNAP-tag technology overcome these challenges by conjugating benzylguanine-modified single-chain fragment variables (scFvs) with 1:1 stoichiometry while preserving antigen binding. Two (human mouse)...
Although current cancer treatment strategies are highly aggressive, they often not effective enough to destroy the collectivity of malignant cells. The residual tumor cells that survived first-line may continue proliferate or even metastasize. Therefore, development novel more specifically eliminate also single is urgently needed. In this respect, antibody-based therapeutics, in particular example immunotoxins, has attracted broad interest. Since internalization immunotoxins essential for...
Antibody-based immunotherapy of leukemia requires the targeting specific antigens on surface blasts. The Fc gamma receptor (CD64) has been investigated in detail, and CD64-targeting shown promising efficacy targeted ablation acute myeloid (AML), myelomonocytic (AMML) chronic cells (CML). Here we investigate for first time potential FcαRI (CD89) as a new target antigen expressed by different leukemic cell populations. For killing, generated recombinant fusion protein comprising an anti-human...
Antibody derivatives, such as the single chain fragment variable (scFv), can be developed diagnostic and therapeutic tools in cancer research, especially form of fusion proteins. Such derivatives are easier to produce modify than monoclonal antibodies (mAbs) achieve better tissue/tumor penetration. The genetic modification scFvs is also much more straightforward challenging chemical mAbs. Therefore, we constructed two derived from approved cetuximab (scFv2112) panitumumab (scFv1711), both...
Antibody-based cancer therapy is a promising approach that increases therapeutic specificity and reduces the side effects associated with standard treatments. CD89 (Fcα receptor, FcαR) transmembrane protein naturally expressed on cells of myeloid lineage, including neutrophils, eosinophils monocytes. It involved in IgA binding, phagocytosis, cytokine release antibody-dependent cell-mediated cytotoxicity (Valerius et al, 1997; Bakema & van Egmond, 2011). Due to natural expression involvement...
The antigen-specific targeting of autoreactive B cells via their unique cell receptors (BCRs) is a novel and promising alternative to the systemic suppression humoral immunity. We generated characterized cytolytic fusion proteins based on an existing immunotoxin comprising tetanus toxoid fragment C (TTC) as component modified Pseudomonas aeruginosa exotoxin A (ETA') cytotoxic component. was reconfigured replace ETA' with either granzyme mutant R201K or MAPTau human effector domains. were...
In vitro and ex vivo development of novel therapeutic agents requires reliable accurate analyses the cell conditions they were preclinical tested for, such as apoptosis. The detection apoptotic cells by annexin V (AV) coupled to fluorophores has often shown limitations in choice dye due interference with other fluorescent-labeled markers. SNAP-tag technology is an easy, rapid versatile method for functionalization proteins was therefore used labeling AV various fluorophores. We generated...
Abstract BACKGROUND The analysis and comparison of global DNA methylation patterns has become a gold standard in modern neuropathology. For human central nervous system (CNS) tumors other cancers, the research community collected thousands profiles, leading to discovery definition numerous molecularly distinct tumor types subtypes. Although reliable preclinical mouse models are essential for understanding development validation therapeutic approaches, such analyses have so far not been...