A5036966030- CAR-T cell therapy research
- Cancer, Hypoxia, and Metabolism
- Lymphoma Diagnosis and Treatment
- ATP Synthase and ATPases Research
- Monoclonal and Polyclonal Antibodies Research
- Endoplasmic Reticulum Stress and Disease
- Connective tissue disorders research
- Cancer-related Molecular Pathways
- Acute Lymphoblastic Leukemia research
- DNA Repair Mechanisms
- RNA modifications and cancer
- Lung Cancer Research Studies
- Chronic Lymphocytic Leukemia Research
- Mitochondrial Function and Pathology
- Cancer therapeutics and mechanisms
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Ubiquitin and proteasome pathways
- Cancer Mechanisms and Therapy
- Neuroendocrine Tumor Research Advances
- RNA Research and Splicing
- Hippo pathway signaling and YAP/TAZ
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Microtubule and mitosis dynamics
University Hospital Cologne
2016-2025
University of Cologne
2014-2025
Düsseldorf University Hospital
2016-2025
Heinrich Heine University Düsseldorf
2016-2025
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2013-2022
Chromatin remodeling complexes are known to modify chemical marks on histones or induce conformational changes in the chromatin order regulate transcription. De novo dominant mutations different members of SWI/SNF complex have recently been described individuals with Coffin–Siris (CSS) and Nicolaides–Baraitser (NCBRS) syndromes. Using a combination whole-exome sequencing, NGS-based sequencing 23 genes, molecular karyotyping 46 previously undescribed CSS NCBRS, we identified de 1-bp deletion...
Loss of TP53 and RB1 in treatment-naïve small cell lung cancer (SCLC) suggests selective pressure to inactivate death pathways prior therapy. Yet, which these remain available SCLC is unknown. Here, through systemic analysis pathway availability SCLC, we identify non-neuroendocrine (NE) be vulnerable ferroptosis subtype-specific lipidome remodeling. While NE resistant, it acquires addiction the TRX anti-oxidant pathway. In experimental settings non-NE/NE intratumoral heterogeneity, non-NE or...
CACNA1D encodes the pore-forming α1-subunit of Cav1.3, an L-type voltage-gated Ca2+-channel. Despite recent discovery two de novo missense gain-of-function mutations in Cav1.3 individuals with autism spectrum disorder (ASD) and intellectual disability has not been considered a prominent ASD-risk gene large scale genetic analyses, since such studies primarily focus on likely-disruptive variants. Here we report characterization third mutation (V401L) patient ASD epilepsy. For functional...
The genetic disorder Kabuki syndrome (KS) is characterized by developmental delay and congenital anomalies. Dominant mutations in the chromatin regulators lysine (K)–specific methyltransferase 2D (KMT2D) (also known as MLL2) demethylase 6A (KDM6A) underlie majority of cases. Although functions these chromatin-modifying proteins have been studied extensively, physiological systems regulated them are largely unknown. Using whole-exome sequencing, we identified a mutation RAP1A that was...
Abstract Small cell lung cancer (SCLC) is a difficult to treat subtype of cancer. One the hallmarks SCLC its almost uniform chemotherapy sensitivity. However, response typically transient and patients frequently succumb within year following diagnosis. We performed transcriptome analysis major human entities. show significant overexpression genes involved in DNA damage response, specifically SCLC. Particularly CHEK1 , which encodes for cycle checkpoint kinase CHK1, significantly...
Wiedemann-Rautenstrauch syndrome (WRS) is a form of segmental progeria presenting neonatally, characterised by growth retardation, sparse scalp hair, generalised lipodystrophy with characteristic local fatty tissue accumulations and unusual face. We aimed to understand its molecular cause.We performed exome sequencing in two families, targeted 10 other families silico modelling studies transcript processing analyses explore the structural functional consequences identified variants.Biallelic...
Abstract Chronic lymphocytic leukemia (CLL) remains an incurable disease. Two recurrent cytogenetic aberrations, namely del(17p), affecting TP53 , and del(11q), ATM are associated with resistance against genotoxic chemotherapy (del17p) poor outcome (del11q del17p). Both del(17p) del(11q) also inferior to the novel targeted agents, such as BTK inhibitor ibrutinib. Thus, even in era of therapies, CLL alterations ATM/p53 pathway a clinical challenge. Here we generated two mouse models Atm -...
DNA double-strand breaks (DSBs) are highly toxic lesions, which, if not properly repaired, can give rise to genomic instability. Non-homologous end-joining (NHEJ), a well-orchestrated, multistep process involving numerous proteins essential for cell viability, represents one major pathway repair DSBs in mammalian cells, and mutations different NHEJ components have been described microcephalic syndromes associated, e.g. with short stature, facial dysmorphism immune dysfunction. By using...
Colobomatous macrophthalmia with microcornea syndrome (MACOM, Online Mendelian Inheritance in Man (OMIM) 602499) is an autosomal dominantly inherited malformation of the eye, which characterized by increased axial length, coloboma iris and optic disc, severe myopia. We performed whole-exome sequencing (WES) two affected individuals from 2p23-p16-linked MACOM family, includes 13 3 generations. As no shared novel variation was found on linked haplotype, we copy number (CNV) analysis comparing...
The molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide novel mechanism in basal keratinocytes zebrafish embryos. A loss-of-function mutation atp1b1a, encoding the beta subunit Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, cell carcinogenesis only occurs when Atp1b1a function is compromised both overlying periderm (resulting epithelial polarity...
DNA double-strand breaks (DSBs) are highly toxic lesions that can lead to chromosomal instability, loss of genes and cancer. The MRE11/RAD50/NBN (MRN) complex is keystone involved in signaling processes inducing the repair DSB by, for example, activating pathways leading homologous recombination nonhomologous end joining. Additionally, MRN also plays an important role maintenance telomeres act as a stabilizer at replication forks. Mutations NBN MRE11 associated with Nijmegen breakage...
Abstract Treatment-naïve small cell lung cancer (SCLC) is typically susceptible to standard-of-care chemotherapy consisting of cisplatin and etoposide recently combined with PD-L1 inhibitors. Yet, in most cases, SCLC patients develop resistance first-line therapy alternative therapies are urgently required overcome this resistance. In study, we tested the efficacy dinaciclib, an FDA-orphan drug inhibitor cyclin-dependent kinase (CDK) 9, among other CDKs, SCLC. Furthermore, report on a newly...
Abstract Cre-recombinase inducible model systems are extensively used in cancer research to manipulate gene expression specific tissues and induce autochthonous tumor growth. These often involve the cross-breeding of genetically engineered organisms containing loxP -flanked alleles with those expressing Cre-recombinase. This approach, while effective, has challenge requiring high numbers animals due breeding requirements. Other frequently induction methods direct application viral vectors....
Cdkn1a, which encodes p21, functions as a major route for p53-mediated cell-cycle arrest. However, the consequence of Cdkn1a gene dosage on tumor suppression has not been systematically investigated. Here, we employed BAC transgenesis to generate Cdkn1aSUPER mouse, harbors an additional allele within its natural genomic context. We show that these mice display enhanced arrest and reduced apoptosis in response genotoxic stress. Furthermore, using chemically induced skin cancer model...
Kabuki syndrome (KS) is a rare developmental disorder characterized by multiple congenital malformations, postnatal growth retardation, intellectual disability, and recognizable facial features. It mainly caused mutations in either KMT2D or KDM6A . We describe 14‐year‐old boy with KS presenting an unusual combination of bilateral microphthalmia orbital cystic venous lymphatic malformation neonatal cholestasis bile duct paucity, addition to the typical clinical features KS. identified novel...
The advent of molecularly targeted therapeutic agents has opened a new era in cancer therapy. However, many tumors rely on nondruggable cancer-driving lesions. In addition, long-lasting clinical benefits from single-agent therapies rarely occur, as most the acquire resistance over time. identification combination regimens interfering with signaling through oncogenically rewired pathways provides promising approach to enhance efficacy single-agent-targeted treatments. Moreover, drug might...
Heterozygous germline mutations in MTOR have been shown to underlie Smith–Kingsmore syndrome, a rare autosomal dominant syndrome characterized by macrocephaly, developmental delay, and dysmorphic facial features. Recently, two unrelated families with the mutation, c.5395G>A p.(Glu1799Lys), were reported. Here, we describe siblings from non‐consanguineous German family whom identified same heterozygous missense mutation . Remarkably, all reported including described herein, healthy parents...