Oliver Harschnitz
A5080771881- Herpesvirus Infections and Treatments
- RNA regulation and disease
- interferon and immune responses
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Peripheral Neuropathies and Disorders
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Long-Term Effects of COVID-19
- Viral Infections and Immunology Research
- Cancer-related gene regulation
- Hereditary Neurological Disorders
- Complement system in diseases
- COVID-19 Clinical Research Studies
- Botulinum Toxin and Related Neurological Disorders
- RNA Research and Splicing
- Genetic Neurodegenerative Diseases
- Tryptophan and brain disorders
- Alzheimer's disease research and treatments
- SARS-CoV-2 and COVID-19 Research
- SARS-CoV-2 detection and testing
- Facial Nerve Paralysis Treatment and Research
- Nerve injury and regeneration
- Barrier Structure and Function Studies
University Medical Center Utrecht
2013-2024
Utrecht University
2018-2024
Kettering University
2018-2024
Human Technopole
2022-2024
Centro de Investigación Biomédica en Red
2020
Brighton and Sussex Medical School
2020
Hospital Universitari i Politècnic La Fe
2020
University Hospital of Basel
2020
University of Basel
2011-2020
Memorial Sloan Kettering Cancer Center
2018
Cerebral organoids are 3D stem cell-derived models that can be utilized to study the human brain. The current consensus is cerebral consist of cells derived from neuroectodermal lineage. This limits their value and applicability, as mesodermal-derived microglia important players in neural development disease. Remarkably, here we show innately develop within a organoid model display characteristic ramified morphology. transcriptome response inflammatory stimulation these organoid-grown...
COVID-19 patients commonly present with signs of central nervous system and/or peripheral dysfunction. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem cells (hPSCs) are selectively susceptible and permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 infection DA triggers an inflammatory cellular senescence response. High-throughput screening in hPSC-derived identified several FDA-approved drugs can rescue the...
Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment CNS cell-intrinsic antiviral immunity. Deficiencies pathway impair immunity to vesicular stomatitis (VSV) and HSV-1 fibroblasts, cortical but not trigeminal neurons. The underlying molecular mechanism is thought involve impaired IFN-α/β induction recognition dsRNA viral intermediates or by-products. However, we show here that human controls constitutive levels IFNB...
Inborn errors of TLR3-dependent type I IFN immunity in cortical neurons underlie forebrain herpes simplex virus-1 (HSV-1) encephalitis (HSE) due to uncontrolled viral growth and subsequent cell death. We report an otherwise healthy patient with HSE who was compound heterozygous for nonsense (R422*) frameshift (P493fs9*) RIPK3 variants. Receptor-interacting protein kinase 3 (RIPK3) is a ubiquitous cytoplasmic regulating death outcomes, including apoptosis necroptosis. In vitro, the R422*...
We investigated the pathogenicity of immunoglobulin M (IgM) anti-GM1 antibodies in serum from patients with multifocal motor neuropathy (MMN) using human induced pluripotent stem cell (iPSC)-derived neurons (MNs).iPSCs were generated fibroblasts and differentiated into MNs. studied binding IgM to MNs, their complement-activating properties, effects on structural integrity fluorescence electron microscopy. Live imaging was used study antibody MNs presence absence complement.IgM detected sera...
Significance We previously demonstrated that induced pluripotent stem cell (iPSC)-derived cortical neurons from HSV-1 encephalitis patients with Toll-like receptor 3 (TLR3) pathway deficiencies are highly susceptible to HSV-1, due impairment of autonomous TLR3-IFN immunity. In this study we present a protocol for efficient derivation/purification trigeminal ganglion (TG) human iPSCs. The resulting TG sensory identity and exhibit robust biological function. also show play distinct roles in...
Inherited deficiency of the RNA lariat–debranching enzyme 1 (DBR1) is a rare etiology brainstem viral encephalitis. The cellular basis disease and range predisposition are unclear. We report inherited DBR1 in 14-year-old boy who suffered from isolated SARS-CoV-2 patient homozygous for previously reported hypomorphic pathogenic variant (I120T). Consistently, I120T/I120T fibroblasts affected individuals this another unrelated kindred have similarly low levels protein high lariats. human...
Most cases of herpes simplex virus 1 (HSV-1) encephalitis (HSE) remain unexplained
To revise the static and dynamic normative values for two-point discrimination test to examine its applicability validity in patients with a polyneuropathy.Two-point threshold were assessed 427 healthy controls 99 mildly affected by polyneuropathy. The divided into seven age groups ranging from 20-29, 30-39,..., up 80 years older; each group consisted of at least 30 men women. Two-point examination took place under standardised conditions on index finger. Correlation studies performed...
The biological pathways involved in amyotrophic lateral sclerosis (ALS) remain elusive and diagnostic decision-making can be challenging. Gene expression studies are valuable overcoming such challenges since they shed light on differentially regulated may ultimately identify biomarkers. This two-stage transcriptome-wide study, including 397 ALS patients 645 control subjects, identified 2,943 expressed transcripts predominantly RNA binding intracellular transport. When batch effects between...
Intermediate-length repeat expansions in ATAXIN-2 (ATXN2) are the strongest genetic risk factor for amyotrophic lateral sclerosis (ALS). At molecular level, ATXN2 intermediate enhance TDP-43 toxicity and pathology. However, whether this triggers ALS pathogenesis at cellular functional level remains unknown. Here, we combine patient-derived mouse models to dissect effects of an background. iPSC-derived motor neurons from ATXN2-ALS patients show altered stress granules, neurite damage abnormal...
Fluorescence microscopy, a key driver for progress in the life sciences, faces limitations due to microscope's optics, fluorophore chemistry, and photon exposure limits, necessitating trade-offs imaging speed, resolution, depth. Here, we introduce MicroSplit, computational multiplexing technique based on deep learning that allows multiple cellular structures be imaged single fluorescent channel then unmix them by means, allowing faster reduced exposure. We show MicroSplit efficiently...
COVID-19 patients commonly present with neurological signs of central nervous system (CNS)1-3 and/or peripheral dysfunction4. However, which neural cells are permissive to infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been controversial. Here, we show that midbrain dopamine (DA) neurons derived from human pluripotent stem (hPSCs) selectively SARS-CoV-2 both in vitro and upon transplantation vivo, triggers a DA neuron inflammatory cellular senescence response....
Background Clinical trials to test safety and efficacy of drugs for patients with spinal muscular atrophy (SMA) are currently underway. Biomarkers that document treatment-induced effects needed because disease progression in childhood forms SMA is slow clinical outcome measures may lack sensitivity detect meaningful changes motor function the period 1–2 years follow-up during randomized trials. Objective To determine compare SMN protein mRNA levels two cell types (i.e. PBMCs skin-derived...
To investigate whether high innate activity of the classical and lectin pathways complement is associated with multifocal motor neuropathy (MMN) levels or potential anti-GM1 antibodies to activate system correlate disease severity.We performed a case-control study including 79 patients MMN matched healthy controls. Muscle weakness was documented Medical Research Council scale sum score axonal loss nerve conduction studies. Activity assessed by ELISA. We also determined serum mannose-binding...