CV Science

Gilles Laverny PATHOPHYSIOLOGICAL ROLE OF VITAMIN D SIGNALLING

Course and current status

After completing a Master's degree in Pharmaceutical Sciences at the University of Strasbourg in 2006, I joined Dr. L. Adorini's laboratory at the biotech company Bioxell, S.p.A., in Milan, Italy to characterize the therapeutic effects of vitamin D analogues, and defended my thesis at the University of Kuopio, Finland (December 2009), as part of the European 'Early Stage Researcher Marie Curie' NucSys program. This multidisciplinary consortium of 18 PhD students from 12 European partners aimed to gain a better understanding of nuclear receptor activity, and gave me the opportunity to build up a network of experts.

After a 1^st post-doctoral internship of 18 months at the Faculty of Pharmacy of Strasbourg on the characterization of the effects of carbon nanotubes, I joined Dr. Metzger's laboratory at the IGBMC. These previous activities allowed me to lead pluridisciplinary projects together with chemist and medical doctors aiming at the identification of new drugs. Since I joined the IGBMC, I am developing a pluridisciplinary research to better understand the pathophysiological roles of vitamin D signaling.

Scientific summary

Group Leader, IGBMC – Institute of Genetics and Molecular and Cellular Biology

Over the past 15 years, I have developed a particular interest on the caracterisation of the natural history and identification of new therapeutic options for rare diseases and cancers. The translational research of my group aims to improve our understanding on disease progression and on the clinical care of refractory diseases.

Projects

The active form of the hormone vitamin D controls calcium and phosphate levels in the body. In addition, it contributes to the regulation of the inflammation and cell proliferation, conferring a protective, even therapeutic, role in various cancers and autoimmune diseases.

To date, the mechanisms underlying the activities of vitamin D have not been elucidated. This lack of understanding limits its clinical use, since the doses required for the treatment of cancers or autoimmune diseases induce hypercalcemia; resulting in calcification of the kidneys, heart and vessels, leading to dysfunction of these organs.

Our group is interested in understanding how vitamin D controls calcium homeostasis and tumor progression. We focus on rare diseases characterized by impaired vitamin D signaling, and on prostate cancer.

We use patient cells and mouse models recapitulating human pathologies, and leverage single-cell and spatial transcriptomic analyses coupled with functional validations.

We also collaborate with chemists and structural biologists to design and characterise new vitamin D analogues with potent therapeutic activities for many diseases that are refractory to current treatments.

Selected Achievements

• unraveled the repressive activities of the unliganded vitamin D receptor (PMID: 25620699)
• led the work that identify a novel mechanisms underlying vitamin D receptor nuclear translocation (PMID: 33288743). 
• caracterised the therapeutic activities of up to 20 vitamin D analogs. 
• shed light on several mechanims underlying disease progression, with a particular emphasis in inflammatory bowel disease, abnormal calcium homeostasis, myositis, and prostate cancer, and identify new therapeutic strategies.

As the scientific coordinator of the IGBMC GenomEast platform, I developed a strong expertise on single cell and spatial transcriptomic analysis.

Funding

I coordinated an ANR JCJC, one ANR PRC and one InCa PlBio, and was partner of 2 ANR PRC. I was granted with various financial support from 'La Ligue Contre le Cancer', 'La fondation ARC', the rare disease networks OSCAR and OrKiD, and the association for the research on prostate cancer.

Innovation and Patents

I filed 3 patents to protect the use of vitamin D analogs for therapeutic purposes and was granted with prematuration projects from the CNRS innovation and the Fondation Maladies Rares/Association Francaise contre les Myopathies.