A5103116204- Dermatology and Skin Diseases
- Renal Diseases and Glomerulopathies
- Renal and related cancers
- Cancer-related molecular mechanisms research
- Systemic Lupus Erythematosus Research
- Mitochondrial Function and Pathology
- Gut microbiota and health
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Asthma and respiratory diseases
- Celiac Disease Research and Management
- Psoriasis: Treatment and Pathogenesis
- ATP Synthase and ATPases Research
- Epigenetics and DNA Methylation
- Pancreatitis Pathology and Treatment
- Mast cells and histamine
- IgG4-Related and Inflammatory Diseases
- Congenital heart defects research
- Genetic and rare skin diseases.
- Atherosclerosis and Cardiovascular Diseases
- Metabolism and Genetic Disorders
- Chronic Kidney Disease and Diabetes
- Pediatric health and respiratory diseases
- Adipose Tissue and Metabolism
- Hedgehog Signaling Pathway Studies
- T-cell and B-cell Immunology
Columbia University Irving Medical Center
2020-2024
University of Lübeck
2013-2023
Columbia University
2022-2023
Institute for Integrative and Experimental Genomics
2019
National Research Centre on Plant Biotechnology
2013
African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play major role this disparity. While 13% carry high-risk recessive genotypes, only fraction these individuals develops FSGS or failure, indicating involvement additional disease modifiers. Here, we show that presence p.N264K missense variant, when co-inherited with G2 allele,...
Pemphigus and systemic lupus erythematosus (SLE) are severe potentially life-threatening autoimmune diseases. They classified as B cell-mediated diseases, both depending on autoreactive CD4+ T lymphocytes to modulate the cell response. Despite reported association of pemphigus SLE, molecular mechanisms underlying their comorbidity remain unknown. Weighted gene co-expression analysis (WGCNA) publicly available microarray data sets cells was performed, identify shared expression signatures...
Scope Of the three human apolipoprotein E ( APOE ) alleles, ε3 allele is most common, which may be a result of adaptive evolution. In this study, we investigated whether genotype affects body weight and energy metabolism through regulation fatty acid utilization. Methods results Targeted replacement mice expressing APOE3 were significantly heavier on low‐ high‐fat diets compared to APOE4 mice. Particularly feeding, food intake dietary yields as well fat mass increased in Fatty mobilization...
Abstract Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics. However, impact gene-environment interactions on phenotypic mostly remains elusive. To address this, we feed 1154 mice an autoimmunity-prone intercross line (AIL) three different diets. We find that diet substantially contributes to variability unmasks additional genetic susceptibility trait loci (QTL). By performing whole-genome sequencing AIL founder...
Abstract The mammalian gut is home to a diverse microbial ecosystem, whose composition affects various physiological traits of the host. Next-generation sequencing-based metagenomic approaches demonstrated how interplay host genetics, bacteria, and environmental factors shape complex clinical outcomes. However, role fungi in these interactions remains understudied. Here, using 228 males 363 females from an advanced-intercross mouse line, we provide evidence that are regulated by genetics. In...
MicroRNAs (miRNAs) are small endogenous non-coding RNAs that control genes at post-transcriptional level. They essential for development and tissue differentiation, such altered miRNA expression patterns linked to the pathogenesis of inflammation cancer. There is evidence genetically controlled similar transcription protein-coding previous studies identified quantitative trait loci (QTL) in liver. So far, little attention has been paid skin. Moreover, epistatic remains unknown. In this...
Recent studies highlight the utility of quantitative trait locus (QTL) mapping for determining contribution host genetics to interindividual variation in microbiota. We previously demonstrated that similar gut microbiota, abundances bacterial taxa skin are significantly influenced by genetic variation. In this study, we analyzed microbiota mice from 15th generation an advanced intercross line using a novel approach extending both 16S rRNA gene copy (DNA) and transcript (RNA) levels, which...
Mutations in mitochondrial DNA (mtDNA) lead to heteroplasmy, i.e., the intracellular coexistence of wild-type and mutant mtDNA strands, which impact a wide spectrum diseases but also physiological processes, including endurance exercise performance athletes. However, phenotypic consequences limited levels naturally arising heteroplasmy have not been experimentally studied date. We hence generated conplastic mouse strain carrying genome an AKR/J (B6-mtAKR) C57BL/6 J nuclear genomic...
Black Americans are 3-4 times more likely to develop nondiabetic kidney disease than other populations. Exclusively found in people of recent African (AFR) ancestry, risk variants Apolipoprotein L1 (APOL1) termed G1 and G2 contribute significantly this increased susceptibility. Our group others showed that a missense variant APOL1, rs73885316 (p.N264K, "M1"), is remarkably protective against APOL1 when co-inherited with the allele. Since distance between M1 only 367 base pairs, we initially...
The experimental autoimmune encephalomyelitis (EAE) is an disease of the central nervous system commonly used to study multiple sclerosis (MS). We combined clinical EAE phenotypes with genome-wide expression profiling in spleens from 150 backcross rats between susceptible DA and resistant PVG rat strains during chronic phase. This enabled correlation transcripts genotypes, other implicated potential genetic causes pathways EAE. detected 2285 quantitative trait loci (eQTLs). Sixty out 599...
The autosomal dominant Hailey disease (HHD) is caused by mutations in the ATP2C1 gene encoding for human secretory pathway Ca2+/Mn2+ ATPase protein (hSPCA1) Golgi apparatus. Clinically, HHD presents with erosions and hyperkeratosis predominantly intertrigines. Here we report an exome next generation sequencing (NGS) based analysis of genes a Greek family 3 patients presenting clinically atypical lesions mainly localized on neck shoulders. By NGS one HHD-patient silico SNP calling filtering...
Mammalian lungs comprise a complex microbial ecosystem that interacts with host physiology. Previous research demonstrates the environment significantly contributes to bacterial community structure in upper and lower respiratory tract. However, influence of genetics on makeup lung microbiota remains ambiguous, largely due technical difficulties related sampling, as well challenges inherent investigating low biomass communities. Thus, innovative approaches are warranted clarify host-microbe...
Non-coding RNAs (ncRNAs) are known to play important functional roles in the cell.However, their identification and recognition genomic sequences remains challenging.In silico methods, such as classification tools, offer a fast reliable way for screening multiple classifiers have already been developed predict well-defined subfamilies of RNA.So far, however, out all ncRNAs, only tRNA, miRNA snoRNA can be predicted with satisfying sensitivity specificity.We here present ptRNApred, tool detect...
Abstract The impact of environmental factors, such as diet, and the genetic basis autoimmune pancreatitis (AIP) are largely unknown. Here, we used an experimental murine AIP model to identify contribution diet development, well fine‐map AIP‐associated genes in outbred mice prone develop disease. For this purpose, fed autoimmune‐prone intercross line (AIL) three different diets (control, calorie‐reduced western diet) for 6 months, at which point were genotyped phenotyped AIP. Overall, 269 out...
Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and characterized by generation of autoantibodies against hemidesmosomal proteins BP180 (type XVII collagen) BP230. Most intriguingly, BP distinct from other diseases because it predominantly affects elderly individuals above age 75 years, raising question why clinical lesions emerges mostly in this later stage life, even harboring known putative BP-associated germline gene variants. The mitochondrial genome...
Identifying the genetic basis of complex diseases, such as rheumatoid arthritis, remains a challenge that requires experimental models to reduce and environmental variability. Numerous loci for arthritis have been identified in induced animal models; however, few spontaneous genetically studied. Therefore, we generated four-way advanced intercross line (AIL) from four inbred strains, including BXD2/TyJ which spontaneously develops autoimmune arthritis. A genome-wide scan was performed cohort...
Abstract The G protein‐coupled receptor 15 (GPR15) regulates homing of different T‐cell populations into the gut, thus, preserving tissue homeostasis. Its potential role in preservation homeostasis on other body interfaces, including skin, is less well understood. We addressed impact GPR15 cutaneous and skin microbiome under steady‐state conditions. Genetic deficiency substantially altered composition skin‐resident populations. Precisely, dendritic epidermal T cells were almost absent...
Abstract Psoriasis is a chronic inflammatory skin condition. Repeated epicutaneous application of Aldara® (imiquimod) cream results in psoriasiform dermatitis mice. The Aldara®‐induced (AIPD) mouse model has been used to examine the pathogenesis psoriasis. Here, we forward genetics approach which compared AIPD that developed 13 different inbred strains identify genes and pathways modulated disease severity. Among our primary results, found severity differed substantially between mice these...
To gain insight into the pathogenesis of collapsing glomerulopathy, a rare form FSGS that often arises in setting viral infections, we performed genome-wide association study (GWAS) among inbred mouse strains using murine model HIV-1 associated nephropathy (HIVAN).
Summary Mutations in mitochondrial DNA (mtDNA) lead to heteroplasmy, i.e. the intracellular coexistence of wild-type and mutant mtDNA strands, which impact a wide spectrum diseases but also physiological processes, including endurance exercise performance athletes. However, phenotypic consequences limited levels naturally-arising heteroplasmy have not been experimentally studied date. We hence generated conplastic mouse strain carrying genome AKR/J (B6-mt AKR ) together with C57BL/6J nuclear...