Research Director at Inserm, Scientific Manager of the Center’s diabetes genomic medicine programs, head of the EquipEx LIGAN-PM and team leader at UMR 1283/8199

Today, Dr Amélie BONNEFOND tells us about her research projects within PreciDIAB and the central role of its LIGAN-PM platform in the development of precision medicine.

“Can you tell us about your background and what brought you to work in research, especially in the field of genetics? ”

I took a preparatory class in Grenoble after the baccalaureate and then I joined an agronomy school in Montpellier. After the intellectual turmoil of the prep class, the agro training bored me greatly. So I decided to take a master’s degree in Biology and Health at the same time as my school. I really enjoyed the internships in the laboratory and decided to continue with a thesis. The choice of genetics, on the other hand, was pure chance.

For my thesis, I primarily chose the laboratory rather than the theme of genetics. Indeed, I wanted to land in a dynamic and abundant laboratory, which perfectly characterized Philippe Froguel’s laboratory in Lille. So I decided to leave the south for the far north and get into human genetics.

“ Quelles sont les avancées majeures de ces dernières années en médecine de précision et quelles sont les perspectives d’avenir pour la prise en charge des patients diabétiques ? ”

Genetics has become a flagship tool in precision medicine, the objective of which is to determine the etiological factors specific to each patient in order to deduce personalized and optimal care. In the context of diabetes, it is above all to prevent the development of kidney, eye, cardiovascular and cancer complications which can be formidable. There are today two main genetic approaches turned to this modern medicine; both are based on advanced, robust and robotic technology, which we have been able to develop for more than 10 years thanks in particular to our Equipment of Excellence (EquipEx) LIGAN.

The first approach is based on high throughput sequencing and aims to identify rare and pathogenic mutations in genes involved in highly hereditary forms of diabetes, transmitted to each generation. Some of these genes are said to be actionable; In other words, when we find a pathogenic mutation in one of these genes in a diabetic patient, we can completely adapt and improve their management. For example, in a diabetic patient, if we identify a pathogenic mutation in the glucokinase gene (which was found to be involved in diabetes in 1992 by Philippe Froguel’s team), anti-diabetes treatments such as insulin or oral hypoglycemic drugs may be stopped. My work is largely focused on the effects of rare variants in the determinism of metabolic diseases such as diabetes and obesity, which has just been recognized by the 2021 Minkowski Prize from the European Diabetes Society.

The second genetic approach used in the context of precision medicine is a bit more complex. It consists of using frequent genetic variants associated with diabetes (which are detected via DNA chips) and multiple clinical data (such as weight, glycemia, insulinemia, lipids, etc.) in order to group patients together. diabetics in homogeneous subgroups of patients who will respond to specific care and treatment. This strategy was developed because diabetes is an extremely heterogeneous disease. We believe that identifying new diabetes subtypes based on genetic and clinical traits will improve patient care.

“Your team is therefore particularly involved in the development of precision medicine. What are your flagship projects at the Center National PreciDIAB? ”

We are working hand in hand with all the doctors and clinicians involved in the network of the National Center PreciDIAB who are in the process of building patient cohorts on which we will be able in particular to apply the two genetic approaches that I have just mentioned. PreciDIAB also has a European development and we are working with Professor Nicolas Paquot who heads the endocrinology department of the CHU de Liège.

We analyze the entire active file of diabetic patients visiting this department, which represents more than 4000 patients. We plan to carry out an interventional study in these patients using our genetic approaches and then to evaluate the clinical and economic consequences of these approaches, compared to traditional management. At the same time, we will be looking for new genes involved in diabetes and associated diseases.