A5041896108- Congenital Heart Disease Studies
- CAR-T cell therapy research
- Circadian rhythm and melatonin
- Genetic Neurodegenerative Diseases
- Neurobiology and Insect Physiology Research
- T-cell and B-cell Immunology
- Cardiac Structural Anomalies and Repair
- Immunotherapy and Immune Responses
- Glioma Diagnosis and Treatment
- Cardiac tumors and thrombi
- Tryptophan and brain disorders
- Insect and Arachnid Ecology and Behavior
- Coronary Artery Anomalies
- Single-cell and spatial transcriptomics
- Vascular anomalies and interventions
- Mitochondrial Function and Pathology
- Immune Cell Function and Interaction
- Pulmonary Hypertension Research and Treatments
- Photoreceptor and optogenetics research
- Cardiac Arrhythmias and Treatments
- Light effects on plants
- Renal and related cancers
- vaccines and immunoinformatics approaches
- Myasthenia Gravis and Thymoma
- Genetics, Aging, and Longevity in Model Organisms
German Cancer Research Center
2017-2025
Heidelberg University
2018-2025
University Hospital Heidelberg
2020-2024
University Medical Centre Mannheim
2020-2024
Deutschen Konsortium für Translationale Krebsforschung
2024
Heidelberg University
2022
University of Leicester
2009-2020
DKFZ-ZMBH Alliance
2017-2020
Wayne State University
1974-1990
Children's Hospital of Michigan
1975-1987
Substitution of lysine 27 to methionine in histone H3 (H3K27M) defines an aggressive subtype diffuse glioma. Previous studies have shown that a H3K27M-specific long peptide vaccine (H3K27M-vac) induces mutation-specific immune responses control H3K27M+ tumors major histocompatibility complex-humanized mice. Here we describe first-in-human treatment with H3K27M-vac eight adult patients progressive midline glioma on compassionate use basis. Five received combined anti-PD-1 based physician's...
The identification of patient-derived, tumor-reactive T cell receptors (TCRs) as a basis for personalized transgenic therapies remains time- and cost-intensive endeavor. Current approaches to identify TCRs analyze tumor mutations predict activating (neo)antigens use these either enrich infiltrating lymphocyte (TIL) cultures or validate individual autologous therapies. Here we combined high-throughput TCR cloning reactivity validation train predicTCR, machine learning classifier that...
Significance Neurodegenerative diseases such as Alzheimer’s (AD), Parkinson’s (PD), and Huntington’s (HD) present a significant increasing burden on society. Perturbations in the kynurenine pathway (KP) of tryptophan degradation have been linked to pathogenesis these disorders, thus manipulation this may therapeutic relevance. Here we show that genetic inhibition two KP enzymes—kynurenine-3-monooxygenase tryptophan-2,3-dioxygenase (TDO)—improved neurodegeneration other disease symptoms fruit...
Abstract Many higher animals have evolved the ability to use Earth’s magnetic field, particularly for orientation. Drosophila melanogaster also respond electromagnetic fields (EMFs), although reported effects are quite modest. Here we report that negative geotaxis in flies, scored as climbing, is disrupted by a static EMF, and this mediated cryptochrome (CRY), blue-light circadian photoreceptor. CRYs may sense EMFs via formation of radical pairs electrons requiring photoactivation flavin...
Effective, unbiased, high-throughput methods to functionally identify both class II and I HLA-presented T cell epitopes their cognate receptors (TCRs) are essential for prerequisite diagnostic therapeutic applications, yet remain underdeveloped. Here, we present T-FINDER [T Functional Identification (Neo)-antigen Discovery of Epitopes Receptors], a system rapidly deconvolute CD4 CD8 TCRs targets physiologically processed presented by an individual's unmanipulated, complete human leukocyte...
The blue-light sensitive photoreceptor cryptochrome (CRY) may act as a magneto-receptor through formation of radical pairs involving triad tryptophans. Previous genetic analyses behavioral responses Drosophila to electromagnetic fields using conditioning, circadian and geotaxis assays have lent some support the pair model (RPM). Here, we describe new method that generates consistent reliable differ substantially from those already reported. We used Schuderer apparatus isolate local...
H3K27M, a driver mutation with T and B cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma poor survival. We functionally dissect the immune response one patient treated H3K27M peptide vaccine who subsequently entered complete remission. The robustly expanded class II human leukocyte antigen (HLA)–restricted peripheral H3K27M-specific cells. Using functional assays, we characterized 34 clonally unique H3K27M-reactive receptors identified critical, conserved...
The ecosystem of brain tumors is considered immunosuppressed, but our current knowledge may be incomplete. Here we analyzed clinical cell and tissue specimens derived from patients presenting with glioblastoma or nonmalignant intracranial disease to report that the cranial bone (CB) marrow, in juxtaposition treatment-naive tumors, harbors active lymphoid populations at time initial diagnosis. Clinical anatomical imaging, single-cell molecular immune profiling quantification tumor reactivity...
Abstract Huntington’s disease is a progressive neurodegenerative disorder caused by polyglutamine-expanded mutant huntingtin (mHTT). Here, we show that the deubiquitinase Usp12 rescues mHTT-mediated neurodegeneration in rodent and patient-derived human neurons, Drosophila . The neuroprotective role of may be specific amongst related deubiquitinases, as closely homolog Usp46 does not suppress toxicity. Mechanistically, identify potent inducer neuronal autophagy. overexpression accelerates...
Significance The study of laboratory-generated circadian locomotor activity patterns Drosophila played a critical role in determining how fruitfly (and mammalian) clocks function. However, recent observations fly the wild challenged many assumptions about clock might work. A new prominent summer component emerged called “A” (afternoon), which replaced laboratory “siesta.” has been criticized by others to be an artifact, but our here shows that it is genuine and observed under variety...
Abstract T cell receptor-engineered cells (TCR-T) could be advantageous in glioblastoma by allowing safe and ubiquitous targeting of the glioblastoma-derived peptidome. Protein tyrosine phosphatase receptor type Z1 (PTPRZ1), is a clinically targetable antigen associated with stemness. Here, we identify therapeutic HLA-A*02-restricted PTPRZ1-reactive TCR retrieved from vaccinated patient. Single-cell sequencing primary brain tumors shows PTPRZ1 overexpression malignant cells, especially stem...