A5075707992- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sperm and Testicular Function
- Animal Genetics and Reproduction
- Sexual Differentiation and Disorders
- Genomics and Chromatin Dynamics
- BRCA gene mutations in cancer
- Renal and related cancers
- Genetics and Neurodevelopmental Disorders
- Glaucoma and retinal disorders
- RNA Research and Splicing
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Pulmonary Hypertension Research and Treatments
- Cerebrovascular and genetic disorders
- Chromosomal and Genetic Variations
- Pancreatic and Hepatic Oncology Research
- Heat shock proteins research
- Cancer-related Molecular Pathways
- Retinal Diseases and Treatments
- Genomic variations and chromosomal abnormalities
- Epigenetics and DNA Methylation
- DNA Repair Mechanisms
- Cannabis and Cannabinoid Research
- Immune cells in cancer
- RNA and protein synthesis mechanisms
- Genetics, Aging, and Longevity in Model Organisms
University of Colorado Boulder
2024
Medizinische Hochschule Hannover
2011-2023
Princess Máxima Center
2023
Leiden University Medical Center
2018
University of Göttingen
2014
University of Catania
2010
The pathogenetic role of angiogenesis in interstitial lung diseases (ILDs) is controversial. This study represents the first investigation spatial complexity and molecular motifs microvascular architecture important subsets human ILD. aim our was to identify specific variants neoangiogenesis three common pulmonary injury patterns We performed comprehensive compartment-specific analysis 24 explants with usual intersitial pneumonia (UIP), nonspecific (NSIP) alveolar fibroelastosis (AFE) using...
The universal importance of iron, its high toxicity, and complex chemistry present a challenge to biological systems in general protected compartments particular. mitotic rate avid mitochondriogenesis developing male germ cells imply iron requirements. Yet access is tightly regulated by the blood-testis barrier that protects meiotic postmeiotic cells. To elucidate how supplied cells, we analyzed deposition transport proteins testes mice with overload genetic ablation regulators Hfe...
NGS-based multiple gene panel resequencing in combination with a high resolution CGH-array was used to identify genetic risk factors for hereditary breast and/or ovarian cancer 237 patients who were previously tested negative pathogenic BRCA1/2 variants. All screened variants 94 different predisposing genes. We identified 32 14 genes (ATM, BLM, BRCA1, CDH1, CHEK2, FANCG, FANCM, FH, HRAS, PALB2, PMS2, PTEN, RAD51C and NBN) 30 (12.7%). Two BRCA1 that undetected due less comprehensive sensitive...
The Hspa4l gene, also known as Apg1 or Osp94, belongs to the HSP110 heat shock gene family, which includes three genes encoding highly conserved proteins. This study shows that is expressed ubiquitously and predominantly in testis. protein spermatogenic cells, from late pachytene spermatocytes postmeiotic spermatids. In kidney, restricted cortical segments of distal tubules. To physiological role this vivo, we generated mice deficient by targeting. Hspa4l-deficient were born at expected...
Human precision-cut lung slices (PCLS) have proven to be an invaluable tool for numerous toxicologic, pharmacologic, and immunologic studies. Although a cultivation period of <1 week is sufficient most studies, modeling complex disease mechanisms investigating effects long-term exposure certain substances require periods that are much longer. So far, data regarding tissue integrity cultivated PCLS incomplete. More than 1500 human from 16 different donors were under standardized, serum-free...
Mutations in the cationic trypsinogen (PRSS1), cystic fibrosis transmembrane conductance regulator (CFTR), serine protease inhibitor Kazal type 1 (SPINK1), and chymotrypsin C (CTRC) genes are associated with an elevated risk for chronic pancreatitis, which is a known factor pancreatic cancer (PC). Therefore, we analyzed whether PRSS1, CFTR, SPINK1, and/or CTRC mutations adenocarcinoma.The study cohort was composed of 121 PC patients, whom 74 were classified as having 102 patients idiopathic...
Creb3l4 belongs to the CREB/ATF family of transcription factors that are involved in mediating response intracellular signaling. This study shows is expressed at low levels all organs and different stages embryogenesis but present very high testis, particularly postmeiotic male germ cells. In contrast CREB3L4 human prostate, which specific expression was detected, transcripts mouse prostate could be detected only by RT-PCR. To identify physiological function Creb3l4, murine gene inactivated...
Congenital anomalies of the kidneys and urinary tract (CAKUT) are most common cause chronic kidney disease in children. As CAKUT is a genetically heterogeneous disorder cases unexplained, we aimed to identify new causing genes. Using whole-exome sequencing trio-based de novo analysis, identified novel heterozygous frameshift variant leukemia inhibitory factor receptor (LIFR) gene instability mRNA patient presenting with bilateral requiring transplantation at one year age. LIFR encodes...
We have studied the structure, organization, and evolution of human TSPY gene family by mapping three sequence variants identified through RT-PCR analysis onto genomic clones derived from two different YAC contigs. members occur in at least six locations on Y chromosome, each cluster contains a unique combination variants. Our data further suggest that an 18-bp tandem duplication found exon 1 originated unequal sister chromatid exchange between tandemly arranged clusters.
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 wide range predisposition genes have been conducted on cohorts women breast fulfilling Li-Fraumeni(-like) clinical diagnostic criteria. To specifically help explain gap wild-type cases, we performed array-based CGH (comparative genomic hybridization) and panel-based...
To generate an animal model that is suitable for the analysis of regulation and expression human testis-specific protein, Y-encoded TSPY, a transgenic mouse line, TgTSPY9, harboring complete structural TSPY gene was generated. Fluorescence in situ hybridization Southern analyses show approximately 50 copies transgene are integrated at single chromosomal site maps to distal long arm Y chromosome. The correctly transcribed spliced according pattern mainly expressed testicular tissue, with...
GT198, located 470 kb downstream of BRCA1, encodes for the nuclear PSMC3-interacting protein, which functions as co-activator steroid hormone-mediated gene expression, and is involved in RAD51 DMC1-mediated homologous recombination during DNA repair double-strand breaks. Recently, germline variants GT198 have been identified hereditary breast ovarian cancer (HBOC) patients, mainly cases with early-onset. We screened a cohort 166 BRCA1/2 mutation-negative HBOC 56 developed early-onset before...
Sphingolipids have long been of interest to the scientific community for their roles in eukaryotic cell structuring and disease pathology. Less is known about occurrence function these diverse compounds bacterial domain life, with most studies on sphingolipids focused research host-pathogen or host-symbiont interactions. Thus, contributions environmental sphingolipid pools are poorly understood lipids outside pathogenicity remains largely unexplored. This report marks first instance...
TSPY encodes the testis-specific protein Y-linked. In man, expression of is restricted to testis, where expressed in spermatogonia, primary spermatocytes, and round spermatids, prostate gland. There circumstantial evidence that involved spermatogonial proliferation gonadal tumorigenesis. Because laboratory mouse carries Tspy gene a naturally silenced state (Tspy-ps), we previously restored activity mice generated transgenic line which organization human transgene follow pattern. present...
The LEW/Ztm-ci2 rat is an animal model for syndromal deafness that arose from a spontaneous mutation. Homozygous animals show locomotor abnormalities like lateralized circling behavior. Additionally, impaired vision can be observed in some through behavioral studies. Syndromal as well retinal degeneration are features of the Usher syndrome humans. In present study, mutation was identified base substitution (T->C) exon 56 Myo15, leading to amino acid exchange leucine (Leu) proline (Pro)...
We have isolated both a full-length rat <i>Tspy </i>cDNA from testicular mRNA by <b>r</b>apid <b>a</b>mplification of <b>c</b>DNA <b>e</b>nds (RACE) and RT-PCR </i>gene genomic DNA PCR. In contrast to the mouse, where </i>is present in single copy is apparently functionless, man cattle, TSPY organized moderately repetitive cluster, </i>locus consists one complete functional truncated, probably nonfunctional, copy,...
The human TSPY is the putative gene for gonadoblastoma locus on Y chromosome (GBY). Various molecular, pathological and transgenic mouse studies suggest that a Y-located proto-oncogene contributing to initiation/progression in cancers, including germ cell tumors various somatic such as prostate liver cancer, melanoma. TgTSPY9 line harbors 8.2-kb structural gene, which tandemly integrated chromosome, expressed similar pattern of endogenous genome. This model offers an opportunity examine its...
Molecular aspects of murine evolution were studied by sequencing, and subsequently comparing, introns the Y-chromosomal <i>tspy</i> genes from <i>Apodemus agrarius, A. sylvaticus, flavicollis</i>, <i>Mus platythrix</i> (subgenus <i>Pyromys</i>), <i>M. booduga</i> <i>Leggada</i>), species subgenus <i>Mus</i>, including cervicolor, M. macedonicus</i> <i>M.</i><i>spretus</i>....
TSPY (testis-specific protein, Y-encoded) genes are expressed in premeiotic germ cells and round spermatids. The topology timing of expression, also its homology to members the TTSN-family, suggest that is a proliferation factor for cells. There evidence role aetiology testis cancer. candidate GBY, elusive gonadoblastoma locus on human Y chromosome, which thought predispose dysgenetic gonads 46, XY sex-reversed females develop gonadoblastoma. We have previously generated transgenic mouse...