A5040996207- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Epigenetics and DNA Methylation
- Sperm and Testicular Function
- Sexual Differentiation and Disorders
- Congenital heart defects research
- Barrier Structure and Function Studies
- Neonatal and fetal brain pathology
- Neurological Disease Mechanisms and Treatments
- Hormonal Regulation and Hypertension
- Ubiquitin and proteasome pathways
- Testicular diseases and treatments
- Autophagy in Disease and Therapy
- CAR-T cell therapy research
- Cancer-related gene regulation
- Reproductive Biology and Fertility
- Cellular transport and secretion
- Estrogen and related hormone effects
- Drug Transport and Resistance Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Adrenal and Paraganglionic Tumors
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Viral Infectious Diseases and Gene Expression in Insects
Roche Pharma AG (Germany)
2019
Helsinki University Hospital
2013-2017
University of Helsinki
2013-2017
Washington University in St. Louis
2013-2016
St. Louis Children's Hospital
2011-2014
Helsinki Children's Hospital
2013
Mannheim University of Applied Sciences
2011-2012
University of Applied Sciences Biberach
2012
Conditional deletion of Gata4 in Sertoli cells (SCs) adult mice has been shown to increase permeability the blood-testis barrier (BTB) and disrupt spermatogenesis. To gain insight into molecular underpinnings these phenotypic abnormalities, we assessed impact gene silencing cell culture models. Microarray hybridization identified genes dysregulated by siRNA-mediated inhibition TM4 cells, an immortalized mouse SC line. Differentially expressed were validated quantitative RT-PCR analysis...
The aim of this study was to characterize the hCMEC/D3 cell line, an in vitro model human Blood Brain Barrier (BBB) for expression brain endothelial specific claudins-3 and -12.hCMEC/D3 cells express -12. Claudin-3 is distinctly localized TJ whereas claudin -12 observed perinuclear region completely absent from TJs. We show that both proteins lost passage numbers where BBB properties are no longer fully conserved. Expression localization claudin-3 not modulated by simvastatin shown improve...
Transcription factor GATA4 is expressed in somatic cells of the mammalian testis. Gene targeting studies mice have shown that essential for proper differentiation and function Sertoli cells. The role Leydig cell development, however, remains controversial, because targeted mutagenesis experiments not a consistent phenotype, possibly due to context-dependent effects or compensatory responses. We therefore undertook reductionist approach study Using microarray analysis quantitative RT-PCR, we...
Abstract Transcription factor GATA6 is expressed in the fetal and adult adrenal cortex has been implicated steroidogenesis. To characterize role of transcription adrenocortical development function, we generated mice which Gata6 was conditionally deleted using Cre-LoxP recombination with Sf1-cre. The glands conditional knockout (cKO) were small had a thin cortex. Cytomegalic changes evident cKO glands, chromaffin cells ectopically located at periphery glands. Corticosterone secretion...
DNA methylation is a mechanism for long-term transcriptional regulation and required normal cellular differentiation. Failure to properly establish or maintain patterns leads cell dysfunction diseases such as cancer. Identifying signatures in complex tissues can be challenging owing inaccurate enrichment methods low yields. We have developed technique called laser capture microdissection-reduced representation bisulfite sequencing (LCM-RRBS) the multiplexed interrogation of status...
In response to gonadectomy certain inbred mouse strains develop sex steroidogenic adrenocortical neoplasms. One of the hallmarks neoplastic transformation is expression GATA4, a transcription factor normally present in gonadal but not adrenal cells adult mouse. To show that GATA4 directly modulates tumorigenesis and merely marker gonadal-like differentiation neoplasms, we studied mice with germline or conditional loss-of-function mutations Gata4 gene. Germline haploinsufficiency was...
Testicular Leydig cells produce androgens essential for proper male reproductive development and fertility. Here, we describe a new cell ablation model based on Cre/Lox recombination of mouse Gata4 Gata6 , two genes implicated in the transcriptional regulation steroidogenesis. The testicular interstitium adult flox/flox ; mice was injected with adenoviral vectors encoding Cre + GFP (Ad-Cre-IRES-GFP) or alone (Ad-GFP). efficiently selectively transduced cells, as evidenced by reporter...
In this issue of Endocrinology, Padua et al (1) characterize the phenotype mice lacking both GATA4 and GATA6 in steroidogenic cells. The double-mutant are born with adrenal aplasia. female pups die from adrenocortical insufficiency, but males survive owing to ectopic corticoid production by adrenal-like cells testis. These mutant shed new light on regulation cell differentiation may provide a model for study testicular rest tumors (TARTs). Steroidogenic cortex testis arise common pool...
Bispecific antibodies (bsAbs) with avidity-enhanced specificity can be used to address target cells increased specificity, ideally binding efficiently that express two cognate antigens, yet not only one of those. Building blocks required generate such bsAbs are binders recognize the antigens high various (including very low monovalent) affinities. The herein described ‘back-to-germline’ (B2G) procedure defines derivatives. It converts parent derivatives retain but modulate affinity. approach...
The aim of this study was to characterize the hCMEC/D3 cell line, an in vitro model human Blood Brain Barrier (BBB) for expression brain endothelial specific claudins-3 and -12. cells express Claudin-3 is distinctly localized TJ whereas claudin -12 observed perinuclear region completely absent from TJs. We show that both proteins lost passage numbers where BBB properties are no longer fully conserved. Expression localization claudin-3 not modulated by simvastatin shown improve barrier...