School of Biomedical Sciences cordially invites you to join the following seminar:

Speaker: Dr Laurence Legeai-Mallet, Director of Research, French National Institute for Health and Medical Research, Imagine Institute, Université de Paris Cité, Paris, France
Talk Title: FGFR-related osteochondrodysplasia disorders and preclinical studies

Date: 2 December 2024 (Monday)
Time: 4:00 pm – 5:00 pm
Venue: Seminar Room 4, 4/F, 3 Sassoon Road
Host: Professor Danny Chan

Biography

Dr Laurence Legeai-Mallet is director of Research at INSERM. She is the head of the Laboratory “Molecular and Physiopathological bases of osteochondrodysplasia” at the Imagine Institute (Paris).

Dr Laurence Legeai-Mallet has been involved in the genetics of skeletal disease since 1993. Her research field ranges from the identification of disease genes involved in cartilage and bone disorders, to the understanding of bone development and skeletal disorders. Her team is also internationally recognized for proof of concept studies and breakthrough preclinical studies in achondroplasia and hypochondroplasia. In 2009, based on several collaborations between her academic laboratory and pharmaceutical companies, she has developed the first therapeutic approaches for osteochondrodysplasias. Indeed, in 2012, she reported with BioMarin the therapeutic potential of a novel C-type natriuretic peptide analog (Vosoritide) as the first investigational therapy for achondroplasia. In 2016, she demonstrated the strong effect of low dose tyrosine kinase inhibitor (Infigratinib) on a Fgfr3 mouse model recapitulating the achondroplasia phenotype, allowing Infigratinib to be in Phase 2 clinical trial today (QED Therapeutics).

Dr Legeai-Mallet current research programs focus on developing new therapeutic approaches for chondrodysplasias and craniosynostoses, and on the understanding the basic cellular and molecular mechanisms underlying skeletal development anomalies in rare skeletal disorders.

Abstract

The fibroblast growth factor receptors (FGFRs) are a family of transmembrane receptor tyrosine kinases. Activation by the ligand fibroblast growth factor (FGF) leads to the intracellular activation of several downstream signaling pathways. The FGFRs and their ligands have a key role during the formation of the skeleton.

In humans, activating FGFR mutations are responsible for a broad spectrum of osteochondrodysplasia diseases that lead to the abnormal development of the craniofacial, axial and appendicular skeleton.

With a view to characterizing the processes involved in skeleton formation, our team has developed a number of mouse models expressing the Fgfr3 gain-of-function mutations associated with achondroplasia and hypochondroplasia, the most frequent dwarfism.

A better understanding of endochondral and membranous processes in these mouse models has enabled us to conduct preclinical studies. Today many therapeutic approaches have been developed and are promising treatments for patients expressing FGFR variants.

ALL ARE WELCOME.