Maximilian Schieck

Hannover Medical School | MHH · Hannover Unified Biobank

The establishment of study standards and compliance with them in multicentre studies is essential to ensure the comparability and reproducibility of the research results obtained from the collected biosamples. In the National Pandemic Cohort Network (NAPKON), a Germany-wide platform for Covid-19 research, standard operating procedures (SOPs) for b...

Inborn errors of immunity (IEI) are genetically driven disorders. With the advancement of sequencing technologies, a rapidly increasing number of gene defects has been identified, thereby mirroring the high heterogeneity in immunological and clinical presentations observed in patients. However, for a large majority of patients, no causative single...

Impressive global efforts have identified both rare and common gene variants associated with severe COVID-19 using sequencing technologies. However, these studies lack the sensitivity to accurately detect several classes of variants, especially large structural variants (SVs), which account for a substantial proportion of genetic diversity includin...

Acute lymphoblastic leukemia (ALL) is the most frequent malignancy in childhood and adolescence. In more than 60% of cases of this heterogeneous disease, a genetic marker is identified via cytogenetic or molecular analyses. TCF3 gene fusions occur in 5-11% of ALL patients. In <1% the TCF3 alteration in ALL leads to a TCF3-HLF fusion gene. Even thou...

Acute lymphoblastic leukemia (ALL) is the most prevalent type of cancer occurring in children. ALL is characterized by structural and numeric genomic aberrations that strongly correlate with prognosis and clinical outcome. Usually, a combination of cyto- and molecular genetic methods (karyotyping, array-CGH, FISH, RT-PCR, RNA-Seq) is needed to iden...

Inhaled corticosteroids (ICS) are the most common asthma controller medication. An important contribution of genetic factors in ICS response has been evidenced. Here, we aimed to identify novel genetic markers involved in ICS response in asthma. A genome-wide association study (GWAS) of the change in lung function after 6 weeks of ICS treatment was...

Background The polymorphism Arg16 in β2-adrenergic receptor (ADRB2) gene has been associated with an increased risk of exacerbations in asthmatic children treated with long-acting β2-agonists (LABA). However, it remains unclear whether this increased risk is mainly attributed to this single variant or the combined effect of the haplotypes of polymo...

Rationale: Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite IC...

PAX5 is a member of the paired box (PAX) family of transcription factors involved in B‐cell development. PAX5 P80R has recently been described as a distinct genetic B‐cell precursor (BCP) ALL subtype with a favorable prognosis in adults. In contrast, an unfavorable outcome has been observed in children. Our aim was to determine the frequency of PAX...

Risk-adapted therapy has significantly contributed to improved survival rates in pediatric acute lymphoblastic leukemia (ALL) and reliable detection of chromosomal aberrations is mandatory for risk group stratification. This study evaluated the applicability of panel-based RNA sequencing and array CGH within the diagnostic workflow of the German st...

Aicardi-Goutières syndrome (AGS) is a hereditary early onset encephalopathy. AGS patients display variable clinical manifestations including intracranial calcification, cerebral atrophy, white matter abnormalities and characteristic leukocytosis as well as a constitutive upregulation of type I IFN production indicative of a type I interferonopathy....

Induced pluripotent stem cells (iPSCs) are a useful tool to investigate pathomechanistic and cellular processes due to their differentiation potential into different somatic cell types in vitro. Here, we have generated iPSCs from an apparently healthy male individual using an integration-free reprogramming method. The resulting iPSCs are pluripoten...

The Renpenning syndrome spectrum is a rare X-linked mental retardation syndrome characterized by intellectual disability, microcephaly, low stature, lean body and hypogonadism. Mutations in the polyglutamine tract binding protein 1 (PQBP1) locus are causative for disease. Here, we describe the generation of an iPSC line from a patient mutated in th...

The cover image is based on the Original Article Genome‐wide association study of inhaled corticosteroid response in admixed children with asthma by Hernandez‐Pacheco et al, DOI: 10.1111/cea.13354.

Background Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome‐wide association studies (GWAS) have b...

Toll-like receptors (TLRs) play a critical role in initiating an immune response to infections. In this study, we examined whether single nucleotide polymorphisms (SNPs) in TLR pathway genes are associated with pulmonary tuberculosis (PTB) in a Moldavian population. Thirty-four SNPs in genes associated with the TLR pathway and two SNPs in ASAP1 gen...

Alzheimer's Disease (AD) is the major cause of dementia in the elderly, and cortical neurons differentiated from patient-derived induced pluripotent stem cells (iPSCs) can recapitulate disease phenotypes such as tau phosphorylation or amyloid beta (Aß) deposition. Here we describe the generation of an iPSC cohort consisting of 2 sporadic AD cases a...

Background: Breast cancer is the most prevalent tumor entity in Li-Fraumeni syndrome. Up to 80% of individuals with a Li-Fraumeni-like phenotype do not harbor detectable causative germline TP53 variants. Yet, no systematic panel analyses for a wide range of cancer predisposition genes have been conducted on cohorts of women with breast cancer fulf...

TH17 cells contribute to the pathogenesis of chronic inflammatory diseases such as asthma and TH17 pathway tagging SNPs were associated with asthma and total serum IgE levels in childhood. In this study genotype-specific effects of these SNPs on the expression of TH17 related molecules were analyzed in peripheral blood mononuclear cells (PBMCs) bef...

Figure S1. Main tumour, infiltration of the capsule and haemangiosis

Figure S2. Likelihood ratio (LR) values (A) and MSI‐low phenotype (B) in both tumour components

Table S1. Antibodies and immunohistochemistry

Table S2. CDH1 PCR primer pairs

Table S3. Copy number alterations (CNAs) in both tumour components

Aim: International collaboration is needed to enable large-scale pharmacogenomics studies in childhood asthma. Here, we describe the design of the Pharmacogenomics in Childhood Asthma (PiCA) consortium. Materials & methods: Investigators of each study participating in PiCA provided data on the study characteristics by answering an online questio...

Recently, a new variant of invasive lobular breast cancer (ILBC) with solid-papillary-like growth pattern has been described. We present a case of ILBC with solid-papillary-like growth pattern in the main tumor mass and classical invasive lobular growth pattern in adjacent satellite foci. The two tumor components were subjected to comprehensive mol...

Background: Exhaled nitric oxide (eNO) is a biomarker of airway inflammation and seems to precede respiratory symptoms, such as asthma in childhood. Identifying genetic determinants of postnatal eNO may aid in unraveling the role of eNO in epithelial function or airway inflammation and disease. Objective: To identify genetic determinants of earl...

Background: Genetic variation may partly explain heterogeneity in response to asthma treatment. Recently, the Pharmacogenomics in Childhood Asthma (PiCA) consortium was initiated to perform large-scale pharmacogenomics studies. Aims: To describe the characteristics of the asthmatic children currently included in PiCA and to assess treatment respons...

Altered metabolism in tumor cells has been a focus of cancer research for as long as a century but has remained controversial and vague due to an inhomogeneous overall picture. Accumulating genomic, metabolomic, and lastly panomic data as well as bioenergetics studies of the past few years enable a more comprehensive, systems-biologic approach prom...

Background: IL-33 polymorphisms influence the susceptibility to asthma. IL-33 indirectly induces Th2-immune responses via dendritic cell activation, being important for development of atopic diseases. Furthermore, IL-33 upregulates regulatory T cells (Tregs), which are critical for healthy immune homeostasis. This study investigates associations b...

Background Asthma is a disease affecting more boys than girls in childhood and more women than men in adulthood. The mechanisms behind these sex-specific differences are not yet understood. Objective We analyzed whether and how genetic factors contribute to sex-specific predisposition to childhood-onset asthma. Methods Interactions between sex...

Chromosome 17q21, harboring the orosomucoid 1-like 3 (ORMDL3) gene, has been consistently associated with childhood asthma in genome-wide association studies. We investigated genetic variants in and around ORMDL3 that can change the function of ORMDL3 and thus contribute to asthma susceptibility. We performed haplotype analyses and fine mapping of...

BACKGROUND: Genomewide association and epigenetic studies found a region within the RAD50 gene on chromosome 5q31 to be associated with total serum IgE levels and asthma. In mice, this region harbors a locus control region for nearby TH 2 cytokines, which is characterized by four Rad50 DNase I hypersensitive sites (RHS4-7). Among these, RHS7 seems...

Previous studies suggested that maternal farm exposure during pregnancy modulates early immune development toward an allergy-protective status potentially mediated by TH1 or regulatory T (Treg) cells. However, the underlying mechanisms might involve immune modulation of additional T-cell populations, such as TH17 cells, influenced by genetic predis...

Laser based transfection methods have proven to be an efficient and gentle alternative to established molecule delivery methods like lipofection or electroporation. Among the laser based methods, gold nanoparticle mediated laser transfection bears the major advantage of high throughput and easy usability. This approach uses plasmon resonances on go...

Asthma is a common inflammatory disease for which the cause is not yet known. Studies of the epidemiology and natural history of childhood asthma into adulthood demonstrate a change in gender prevalence with age. Hormones and inflammation may interact in asthma pathogenesis and determine its course. The same may be true for some endocrine disorders...