Nadine Spielmann
A5077857985- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- Thyroid Disorders and Treatments
- Metabolism and Genetic Disorders
- Salivary Gland Disorders and Functions
- Mitochondrial Function and Pathology
- Genetic Associations and Epidemiology
- RNA modifications and cancer
- Diet and metabolism studies
- Oral microbiology and periodontitis research
- Stress Responses and Cortisol
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Pluripotent Stem Cells Research
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Nuclear Receptors and Signaling
- Heart Rate Variability and Autonomic Control
- Single-cell and spatial transcriptomics
- Oral Health Pathology and Treatment
- Cardiac Fibrosis and Remodeling
- Hippo pathway signaling and YAP/TAZ
- Cell Image Analysis Techniques
- Ion channel regulation and function
Helmholtz Zentrum München
2018-2025
Center for Environmental Health
2023
München Klinik
2021
University of California, Los Angeles
2010-2013
Robert Koch Institute
2010
Sorbonne Université
2008
Centre de Recherche des Cordeliers
2008
Université Paris Cité
2008
Inserm
2008
Délégation Paris 5
2008
Recent studies have demonstrated that discriminatory salivary biomarkers can be readily detected upon the development of systemic diseases such as pancreatic cancer, breast lung and ovarian cancer. However, utility for detection has been undermined due to absence biological mechanistic rationale why distal from oral cavity would lead in saliva. Here, we examine hypothesis tumor-derived exosomes are mechanistically involved cancer-discriminatory transcriptomic biomarkers. We first developed a...
Clinical presentation of congenital heart disease is heterogeneous, making identification the disease-causing genes and their genetic pathways mechanisms action challenging. By using in vivo electrocardiography, transthoracic echocardiography microcomputed tomography imaging to screen 3,894 single-gene-null mouse lines for structural functional cardiac abnormalities, here we identify 705 with arrhythmia, myocardial hypertrophy and/or ventricular dilation. Among these genes, 486 have not been...
Cortical spreading depression (CSD), a wave of depolarization followed by cortical activity, is pathophysiological process implicated in migraine with aura and various other brain pathologies, such as ischemic stroke traumatic injury. To gain insight into the pathophysiology CSD, we generated mouse model for severe monogenic subtype aura, familial hemiplegic type 3 (FHM3). FHM3 caused mutations SCN1A, encoding voltage-gated Na+ channel NaV1.1 predominantly expressed inhibitory interneurons....
Abstract Current concepts regarding the biology of aging are primarily based on studies aimed at identifying factors regulating lifespan. However, lifespan as a sole proxy measure for can be limited value because it may restricted by specific pathologies. Here, we employ large-scale phenotyping to analyze hundreds markers in male C57BL/6J mice. For each phenotype, establish lifetime profiles determine when age-dependent change is first detectable relative young adult baseline. We examine key...
Rare diseases (RDs) are a challenge for medicine due to their heterogeneous clinical manifestations and low prevalence. There is lack of specific treatments only few hundred the approximately 7,000 RDs have an approved regime. Rapid technological development in genome sequencing enables mass identification potential candidates that mutated form could trigger but often not confirmed be causal. Knockout (KO) mouse models essential understand causality genes by allowing highly standardized...
Abstract BACKGROUND Evaluation of the salivary transcriptome is an emerging diagnostic technology with discriminatory power for disease detection. This study explored massively parallel sequencing providing nucleotide-level sequence information each RNA in saliva. METHODS Transcriptome profiling SOLiD™ system was applied to isolated from unstimulated cell-free saliva (CFS) and whole (WS) healthy human volunteers. Sequenced reads were aligned genome build 18 Human Oral Microbiome Database...
Abstract Mouse models are a critical tool for studying human diseases, particularly developmental disorders 1 . However, conventional approaches phenotyping may fail to detect subtle defects throughout the developing mouse 2 Here we set out establish single-cell RNA sequencing of whole embryo as scalable platform systematic genetic models. We applied combinatorial indexing-based 3 profile 101 embryos 22 mutant and 4 wild-type genotypes at embryonic day 13.5, altogether profiling more than...
Schizophrenia is a complex psychiatric disorder with genetic and phenotypic heterogeneity. Accumulating rare genome-wide association study (GWAS) common risk variant information has yet to yield robust mechanistic insight. Leveraging large-scale gene deletion mouse phenomic data thus potential functionally interrogate prioritize human disease genes. To this end, we applied cross-species network-based approach parse an extensive set (188 genes) associated disrupted prepulse inhibition (PPI),...
Abstract The collaborative cross (CC) is a large panel of mouse-inbred lines derived from eight founder strains (NOD/ShiLtJ, NZO/HILtJ, A/J, C57BL/6J, 129S1/SvImJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ). Here, we performed comprehensive comparative phenotyping screening to identify phenotypic differences similarities between the strains. In total, more than 300 parameters including allergy, behavior, cardiovascular, clinical blood chemistry, dysmorphology, bone cartilage, energy metabolism, eye...
Hypertrophic cardiomyopathy (HCM) caused by autosomal-dominant mutations in genes coding for structural sarcomeric proteins, is the most common inherited heart disease. HCM associated with myocardial hypertrophy, fibrosis and ventricular dysfunction. Hypoxia-inducible transcription factor-1α (Hif-1α) central master regulators of cellular hypoxia response HCM. Yet its exact role remains to be elucidated. Therefore, effect a cardiomyocyte-specific Hif-1a knockout (cHif1aKO) was studied an...
Abstract Mouse models play a critical role in cardiology research, offering valuable insights into the molecular mechanisms, genetics, and potential treatments for cardiovascular diseases. However, ability to transfer findings mice between studies is limited by absence of standardized protocols valid reference values assessment normal cardiac function mice. This study aims establish comprehensive transthoracic echocardiography (TTE) ranges mice, particularly focusing on C57BL/6N wildtype...
Hutchinson–Gilford progeria syndrome (HGPS) is a rare, fatal, and premature aging disorder caused by progerin, truncated form of lamin A that disrupts nuclear architecture, induces systemic inflammation, accelerates senescence. While the farnesyltransferase inhibitor lonafarnib extends lifespan limiting progerin farnesylation, it does not address chronic inflammation or senescence-associated secretory phenotype (SASP), which worsens disease progression. In this study, we investigated...
The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that frequently altered range pathologies, including osteoporosis. A total 200 genes were found to significantly affect BMD. This pool BMD comprised 141 previously unknown functions biology and was complementary pools derived recent human studies. Nineteen the also caused skeletal...
Stimulation of ventricular hypertrophy and heart rate are two major cardiac effects thyroid hormone (TH). The aim this study was to determine
<h3>Objectives</h3> Numbers of newly diagnosed HIV infections among men who have sex with (MSM) in Germany increased after the year 2000. We sought to explore trends STI co-infections around time seroconversion patients from German HIV-1 seroconverter cohort 1996–2007. <h3>Methods</h3> MSM were included for secondary analysis, if occurred between 1996 and 2007 a blood sample taken within 2 y infection was available further testing. Samples tested antibodies against <i>Treponema pallidum</i>...
Mouse models are relevant to studying the functionality of genes involved in human diseases; however, translation phenotypes can be challenging. Here, we investigated related monogenic forms cardiovascular disease based on Genomics England PanelApp and aligned them International Phenotyping Consortium (IMPC) data. We found 153 associated with cardiomyopathy, cardiac arrhythmias or congenital heart humans, which 151 have one-to-one mouse orthologues. For 37.7% (57/151), viability data...
Abstract Thyroid hormone (TH) effects are mediated through TH receptors (TRs), TRα1, TRβ1, and TRβ2. The TRs bind to the DNA regulate expression of target genes (canonical signaling). In addition, they mediate activation signaling pathways (noncanonical Whether noncanonical TR action contributes spectrum is largely unknown. aim this study was attribute physiological isoforms their canonical signaling. We conducted multiparameter phenotyping in male female knockout mice (TRαKO, TRβKO), with...
The purpose of this study was to identify regions the human genome linked submaximal exercise heart rates in sedentary state and response a standardized 20-wk endurance training program blacks whites HERITAGE Family Study. A total 701 polymorphic markers covering 22 autosomes were used genome-wide linkage scan, with 328 sibling pairs from 99 white nuclear families 102 115 black family units. Steady-state measured at relative intensity 60% maximal oxygen uptake (HR60) absolute 50 W (HR50)....
Associations between cholesteryl ester transfer protein (CETP) polymorphisms and high-density lipoprotein cholesterol (HDL-c) levels before after 20 wk of endurance training were investigated in the HERITAGE Family Study. Plasma HDL-c, HDL(2)-c, HDL(3)-c, apolipoprotein (apo)A1 measured, 13 CETP single nucleotide (SNPs) genotyped 265 blacks 486 whites. Three haplotypes defined by SNPs at -1337, -971, -629 sites strongly associated with baseline HDL-c Both C-1337T C-629A (P < 0.001) apoA1...
CRELD1 (Cysteine-Rich with EGF-Like Domains 1) is a risk gene for non-syndromic atrioventricular septal defects in human patients. In mouse model, Creld1 has been shown to be essential heart development, particularly septum and valve formation. However, due the embryonic lethality of global knockout (KO) mice, its cell type-specific function during peri- postnatal stages remains unknown.Here, we generated conditional KO mice lacking either endocardium (KOTie2) or myocardium (KOMyHC). Using...