Team Patrice MOLLARD

Networks and rhythms in endocrine glands

Project Pituitary cell networks: function and pathologies

PRINCIPAL INVESTIGATOR

Patrice Mollard
DRCE, CNRS

IGF staff involved
Chrystel LAFONT
IRCN, Inserm
Xavier BONNEFONT
CRCN, CNRS
Agnès MARTIN
CRCN, CNRS
Evelyne GALIBERT
TCN, CNRS
Ana AQUILES
Chercheur CDD, CNRS
Sarah DOS SANTOS
Apprentice Engineer CDD, INSERM

The endocrine pituitary is the ‘master’ gland which is the hormonal relay between the neuroendocrine brain (hypothalamus) and target organs (liver, thyroid, etc.) which regulate basic body functions (growth, metabolism…). Since our group pioneered the discovery of functional 3D networks of pituitary cells, we are now applying both integrated in vivo approaches and single-cell multi-omic studies to explore the function of GH and TSH cell networks in health and disease.

GH cell network and microcirculation

TSH cell network and hypothyroidism

GH cell network and microcirculation

Based on our developments in cellular in vivo imaging of the hypothalamus-pituitary system and local (IPAM platform) and international collaborations, our scientific highlights are:
• Discovery of plasticity features of the GH cell network
• Deciphering the role and dynamics of fenestrated blood capillaries in trans-endothelial exchanges in the pituitary portal system.

Relationship between the GH cell network (green) and pituitary microcirculation (red)

Main publications
• Romanò N., et al. (2023) JCI Insight 8, e165763.
• Le Tissier P., et al. (2022) Endocrinology 163, bqac089.
• Golan M., et al. (2021) Sci Adv 7, eabc8475
• Russell J.P., et al. (2021) Elife 10, e59142.
• Hoa O., et al. (2019) Endocrinology 160, 2271.
• Tommiska J., et al. (2017) Nat Commun 8, 1289.
• Romanò N., et al. (2017) Proc Natl Acad Sci U S A 114, 2379.
• Le Tissier P., et al. (2017) Nat Rev Endocrinol 13, 257.

Funding
• 2018-2023 ANR 2018-GH-Gen – Principal Investigator (PI)
• 2020-2021, PHC Maïmonide (Israël)-Neuropeptide sensors- French PI
• 2019-2022 PhD CNRS-Weismann Institute (Israel) program – French PI
• 2015-2019, ANR 2015-CONACyT (Mexico) Repro-Net- French PI
• 2015-2017 H2020 Marie S. Curie Fellowship Program 2014-GTHREG- PI
• 2013-2017 ANR 2013-Peri-Pulse- PI

Collaborations
• Paul Le Tissier (Edinburgh)
• Cynthia Andoniadou (Londres)
• Tatiana Fiordelisio Coll (Mexico)
• Taneli Raivio (Helsinki)
• Ulrich Boehm (Homburg)
• Jacques Drouin (Montréal)
• Gil Levkowitz (Weizmann Institute of Science, Rehovot)
• Matan Golan (ARO, Rishon Letziyon)

Alumni
• Cassandre Bignaud (PhD student)
• Matan Golan (Post-doc fellow)
• Ombeline Hoa (PhD student)
• Nicola Romanò (Post-doc fellow)

TSH cell network and hypothyroidism

Our group is exploring the role of the network of thyroid stimulating hormone (TSH) cells, the rarest cells in the pituitary gland, as an index of thyroid disorders, which are a major health problem (affecting around 5% of the population). We are exploring:
• the logic of the TSH cell network during hypothyroidism induction (single-nuclei RNA-Seq and Atac-Seq, in vivo imaging, mTSH Elisa and thyroid monitoring, multiscale data analysis and modelling, CRISPR-Cas9 in vivo)
• the potential role of TSH cell network dimorphism in the higher prevalence of thyroid disorders in women (x4-x10 higher that in men)

Hypothalamus-Pituitary-Thyroid axis.

Main publications
• Guillou A., et al. (2023) Endocrinology 165, bqad164.
• Qiao S., et al. (2023) Nat Commun 14, 1098.
• Kemkem Y., et al. (2020) Diabetologia. 63, 1822.
• Campos P., et al. (2020) J Endocrinol 246, R33.
• Le Tissier P., et al. (2018) Endocrinology 159, 3524.

Funding
• 2024-2026 FRM 2023-Post-doc fellowship-MultiscaleTSH – PI
• 2022-2025 ANR 2022-Chameleon – PI
• 2015-2018 FRM 2015-FRM Team-Pituitary thyrotroph organization- PI

Collaborations
• Thomas Moore-Morris & Vincent Compan (IGF, Montpellier)
• Sally Camper (Ann Harbor)
• Frederique Ruf-Zamojski (Los Angeles)
• Dan Bernard (Montréal)
• Paul Le Tissier (Edinburgh)
• Cynthia Andoniadou (Londres)
• Tatiana Fiordelisio Coll (Mexico)

Alumni
• Yasmine Kemkem (Thèse)
• Pauline Campos (Post-doc)
• Luisa Durán Pastén (Post-doc)