| Grant number: | 11/12696-4 |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| Start date: | April 01, 2012 |
| End date: | March 31, 2016 |
| Field of knowledge: | Health Sciences - Medicine - Medical Clinics |
| Principal Investigator: | Bruno Ferraz de Souza |
| Grantee: | Bruno Ferraz de Souza |
| Host Institution: | Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil |
| Associated researchers: | Ana Claudia Latronico Xavier ; Pedro Henrique Silveira Corrêa ; Regina Matsunaga Martin |
| Associated scholarship(s): | 14/03561-6 - Transcription factors vitamin D receptor (VDR) and retinoid X receptor (RXR) genomic location analysis through chromatin immunoprecipitation, BP.IC |
Abstract
Hereditary vitamin D resistant rickets (HVDRR) is an autosomal recessive genetic disorder characterised by early-onset severe hypocalcaemia in the presence of increased serum calcitriol levels. Mutations in the vitamin D receptor (VDR) are the primary molecular defect determining resistance to vitamin D and consequent hypocalcaemia. Nevertheless, in spite of permanent VDR defects, many patients with HVDRR have spontaneous healing of rickets and normalisation of calcemia during periods of increased calcium demand. Indeed, in our service we follow a patient harbouring a severely disrupted VDR (p.R30X mutation) that exhibited spontaneous clinical remission of the disease. The molecular mechanisms of such phenomenon remain elusive. The vitamin D receptor is a nuclear receptor transcription factor expressed almost ubiquitously that regulates gene expression through direct binding to DNA responsive elements once activated by its main ligand, calcitriol. Although many target genes regulated by VDR are known, its full regulatory spectrum is not completely defined, making it hard to identify compensatory regulatory networks involving other steroid-activated nuclear receptors. The aims of this project are: 1) to identify genes regulated by VDR in human cells by comparing the genomic response to calcitriol in the presence and absence of a fully functional VDR through robust techniques such as gene expression microarrays and chromatin immunoprecipitation followed by parallel sequencing (ChIP-Seq); 2) to explore compensatory nuclear receptor networks that might participate in the molecular basis of the observed spontaneous clinical remission of HVDRR. Considering the mounting evidence on the biological functions of calcitriol beyond mineral metabolism, and the growing concern about widespread vitamin D insufficiency in the general population, this investigation will lead to important relevant findings. (AU)
| Articles published in Agência FAPESP Newsletter about the research grant: |
| More itemsLess items |
| TITULO |
| Articles published in other media outlets ( ): |
| More itemsLess items |
| VEICULO: TITULO (DATA) |
| VEICULO: TITULO (DATA) |