Patrick Henriet

Major achievements

• Declining progesterone concentration induces expression of matrix metalloproteinases (MMPs) which are major actors of the endometrial tissue breakdown at menstruation.
• Menstruation-like mechanisms, including release of interleukin-1 alpha and MMPs, contribute to abnormal uterine bleeding.
• Endometrial debris at menstruation express genes involved in cell survival and tissue repair, favoring ectopic implantation of endometriosis lesions.

Question

What are the molecular mechanisms of hormonal regulation in the human endometrium during the menstrual cycle and how are they altered in abnormal uterine bleeding, endometriosis or endometrial cancer?

Research focus

The human uterus is a remarkable organ. During the reproductive life, the endometrium (the uterine mucosa) undergoes regular menstrual cycles consisting of tissue thickening, differentiation and spontaneous self-degradation. The menstrual cycle is controlled by fluctuations of two hormones, estradiol and progesterone. Inappropriate response to these hormones can lead to fertility issues and endometrial diseases such as abnormal uterine bleeding, endometriosis and endometrial cancer. Moreover, progestins (synthetic progesterone-like drugs) are useful for treating endometriosis but fail in a large majority of patients.

Pursuing the work initiated in the 1990’s by Etienne Marbaix on the role of matrix metalloproteinases in menstruation and in abnormal uterine bleeding, the Henriet lab aims to decipher the network of molecular relays modulating in space and time the global control exerted in the human endometrium by estradiol and progesterone, and how their dysfunction can lead to endometrial diseases. Current projects focus on alternative mechanisms of response to progesterone and progestins. Our studies, exclusively dedicated to the human endometrium, typically combine in-depth analyses of hysterectomy specimens with experiments involving various models including cell culture, 3D models and xenografts. Our work benefits from access to state-of-the-art technological platforms, notably for molecular biology and cell and tissue imaging and microscopy.

Patrick Henriet obtained his Master’s degree in Bioengineering from UClouvain in 1989. He then joined the lab of Prof. Yves Eeckhout at the de Duve Institute (called ICP at that time) where he obtained his PhD in in 1994 working on the involvement of matrix metalloproteinases (MMPs) in bone remodeling. For a post-doc, he then moved for 3 years in the lab of Yves De Clerck, in Childrens Hospital Los Angeles (University of Southern California, Los Angeles, USA) to investigate the contribution of MMPs in melanoma. In 1998, he came back to the de Duve Institute to join the group of Etienne Marbaix, Yves Eeckhout and Pierre Courtoy studying the role of MMPs in menstruation, with a more specific project focusing on hormonal control of the menstrual cycle. He became F.R.S-FNRS Research Associate and UCLouvain Associate Professor in 2002. Since 2020, Patrick is full-time Professor at UCLouvain.

Affiliations

• Group leader at de Duve Institute
• Full-time Professor at UCLouvain