Nuclear receptors represent one of the largest families of transcription factors, including 48 identified members in the human genome. Transcriptional activation by most nuclear receptors is controlled by the binding of lipophilic molecules, such as hormones or metabolites including, for example, fatty acids and oxysterols. However, some receptors do not have a known ligand and are thus classified as orphan nuclear receptors. Our knowledge of the regulation of gene expression by nuclear receptors has expanded in recent years, mainly due to the observation that not only is the interaction of the receptor with DNA important in the transcriptional response, but also that coactivators, corepressors and the chromatin environment are crucial in the transmission of hormonal signals to the transcriptional machinery. Given the importance of nuclear receptors in endocrinology for their role in the development of specific diseases, a detailed understanding of their function will have an impact not only on human and animal biology, but also on the development of new drugs for the treatment of endocrine diseases such as breast and prostate cancers, obesity and infertility.
The general projects of the laboratory are:
- To define the role of the LRH-1 nuclear receptor in the implementation of a gene expression program specific to triple negative breast cancer.
- To determine the role of the NR5A2 nuclear receptor in prostate cancer and to evaluate its potential as a therapeutic target.
- To explore the molecular determinants of NR5A1 and NR5A2 nuclear receptors in the ovary and fertility.
- To define the molecular functions of the estrogen receptor in adipose tissue metabolism and its close link with the reproductive system
The approaches used by the laboratory to carry out these different projects are at the cutting edge of molecular and cellular biology. In addition, we make us of our expertise in systems biology, genomics and bioinformatics to respond to different biological questions in an original way.