Endometriosis affects 10-15% of women of reproductive age and is a leading cause of pain and infertility. Endometriosis is commonly associated with inflammation and the estrogen dependent, non-neoplastic spread of endometrial tissue to the peritoneal cavity. While current theories on the causes of endometriosis support a role for physiological dysfunction in the endometrium (i.e. retrograde menstruation), the genetic and molecular mechanisms underlying the etiology of the disease are poorly understood. Recent exome sequencing of endometriotic lesions identified mutations in proteins involved in chromatin remodeling and cell signaling. We hypothesize that mutations in chromatin remodeling and cell signaling pathways activate transcriptional programs required for cellular dissemination and invasion, leading to the estrogen-dependent spread of endometrial tissue.
In Aim 1, we will utilize genetic and genome-wide sequencing approaches to determine the mechanism by which chromatin remodeling regulates normal endometrial epithelial cell identity and homeostasis.
In Aim 2, we will use a newly developed mouse model of endometriosis that mimics the natural spread of endometriotic tissue to address the role of the Activator Protein-1 (AP-1) signaling transcription factor complex in invasion. This proposal will provide insight into the molecular mechanisms that promote the initial establishment and spread of endometriosis.
Endometriosis affects 176 million women worldwide and is a leading cause of pain and infertility. Endometriosis is commonly associated with the non-cancerous growth and dissemination of endometrial tissue in the abdominal cavity. This study will elucidate the molecular mechanisms required for endometrial tissue dissemination in endometriosis.
