Michael Beste (BE postdoctoral)
Dysregulation of apoptosis and inflammatory responsiveness in endometriosis
In healthy human endometrium, cyclic changes in local hormone levels regulate maturation from a proliferative to quiescent cell phenotype. However, endometrial epithelia and stroma in 6-10% of women exhibit reduced hormonal sensitivity, allowing tissue fragments to survive and proliferate following autotransplantation into the peritoneal cavity. Aberrant growth of endometriotic lesions is further aggravated by a chronic inflammatory response that stimulates proteolytic invasion but fails to induce programmed cell death.
Our work aims to understand how cytokine and growth factor signaling in progesterone-resistant endometrium is skewed towards a pro-survival response that protects cells from apoptosis. While many individual pathways have been implicated in persistent survival, we are pursuing network-wide measurements to capture context-specific effects that reveal how cells integrate multiple cues in a complex inflammatory environment. This approach will be applied in comparative models for healthy and diseased endometrium in order to identify effective strategies to interfere with the lesion formation process in women susceptible to endometriosis.