What led you to become a medical researcher?

During my residency, I did a Master 2 in genetics in Corinne Antignac‘s team, a pioneer in the genetics of nephrotic syndromes. It is at the end of this Master 2 that I decided to continue my research work in this laboratory. Thanks to the Institute’s Health-Science program, I was able to carry out a research project while investing 100% of my time in the life of the laboratory.

I chose to do this double degree in medicine and research because, as a clinician, I have to follow young patients with kidney diseases, and research is essential to better understand and treat these diseases. The genetic component in children with kidney failure, sometimes at end-stage, is very important.

Which disease do you particularly focus your work on?

Some children suffer from a condition known as “nephrotic syndrome”, characterized by an inability of the kidneys to retain protein, which is then eliminated in the urine along with waste products. Proteins are essential for the body’s metabolism, and their leakage immediately results in the development of oedemes, characterized by the presence of water in the tissues.

For some of these children, the presence of one or more mutations in genes that are essential for the proper functioning of the kidney is the cause of the disorder. These patients slowly evolve towards end-stage renal failure, and enter a renal transplantation project in the more or less long term. The transplant involves a very heavy immunosuppressive treatment for life. Even in cases of success, a new transplant is needed after a few years, the average life span of a graft being 10-15 years.

How can it be cured?

Trying to find the genetic origin of their disease, thanks to research, is the hope of finding a diagnosis, but also of understanding the mechanisms from a mutation on a gene to the appearance of the clinical expression of the disease (in this case, the genetic nephrotic syndrome). It is by understanding the diseases that we hope to one day be able to offer a treatment adapted to each patient, which will allow them to keep their own kidney and avoid transplants and treatments associated with them.

The discovery of a gene at the origin of a severe form of cortico-resistant nephrotic syndrome: the hope of a better life.

What was your role?

As part of the Health-Science program I discovered a new gene in 2018 that causes a severe and early form of corticosteroid nephrotic syndrome. It adds to the panel of genes analyzed in patients with this syndrome. Some patients will therefore have their diagnosis clarified, and for families with a deleterious variant of this gene, genetic counseling will be offered in order to identify whether other family members are likely to transmit the variant, and also to suggest a prenatal diagnosis in the case of a particularly severe form.

What are the next steps?

Since this discovery, in parallel to research on understanding the mechanisms that lead to hereditary kidney diseases, we are developing a new line of research in the laboratory centered around treating these diseases. These discoveries, and the dynamics of ongoing research, are a source of hope for the sick children and their families, signs of hope that are regularly shared with them in consultation.

L’article Guillaume DORVAL est apparu en premier sur Institut Imagine.

What led you to join Institut Imagine?

I obtained my PhD in 2004 under the supervision of Dr Geneviève de Saint-Basile, Inserm Research Prize 2011. I then did my postdoctoral training in Gary Koretzky’s laboratory at the Abramson Family Cancer Research Institute at the University of Pennsylvania in the USA. In 2007, I decided to come back to France. I joined INSERM and became part of the Institut Imagine.

Which diseases does your laboratory focus on?

With Fernando Sepulveda (CNRS Researcher of Chilean origin), I co-direct the “Molecular bases of immune homeostasis anomalies” laboratory at Institut Imagine. Our team is studying the different mechanisms that allow the immune response to return to a state of equilibrium after being stimulated. Severe alterations in “immune homeostasis” are the source of many immune pathologies. Our team is composed of 12 people: Researchers, young Post-doctoral Researchers, Engineers, Students and French and international Clinicians.

Our research work is at the interface of immunology, cell biology and genetics. Our objective is to determine the pathophysiological mechanisms that are at the origin of severe alterations of immune homeostasis based on the study of immune pathologies caused by a genetic defect. This approach offers unique opportunities to describe key physiological processes, to understand complex mechanisms and to develop new diagnostic and therapeutic tools with the ultimate goal of providing patients with a solution to relieve and cure them.

It is in this context that we have developed a research project on the identification of new molecular determinants controlling allergy responses. Allergic reactions are the consequences of an inappropriate immune response against harmless antigens called allergens.

Today, in France, 1 in 3 people are affected by allergies. By 2050, the most alarming forecasts are that 1 in 2 people will be affected.

These attacks can be benign, but sometimes much more disabling and severe (asthma, strict diet, or angioedema that can lead to death).

What does Institut Imagine bring to you?

Our research on so-called “rare” genetic immune diseases is now being used to understand allergic diseases and to find possible therapeutic approaches.

“Searching for each child, finding for all” is what we do every day at Imagine because research on genetic diseases benefits all medical knowledge on the human body and its pathologies.

I have also worked extensively on the Griscelli syndrome, which owes its name to the founder of Institut Imagine. This genetic disease is characterized by a partial albinism and a silver-gray coloring of the hair, which may be associated with a neurological disorder or an immune pathology characterized by the occurrence of a hemophagocytic syndrome*.

All this research is made possible by Institut Imagine. We are at the heart of a unique environment, in direct contact with patients, their families and doctors, but also with all the other researchers at the Institute who work on all genetic diseases. This multidisciplinary ecosystem is extremely rich and dynamic, and brings a lot to our thinking, our research and our discoveries.
It is therefore a pride and a privilege to be part of the large Imagine family.

*A rare and severe disorder caused by an exaggerated proliferation of T cells and macrophages associated with a very high secretion of pro-inflammatory cytokines known as a cytokine storm, which can be life threatening.

L’article Gaël MÉNASCHÉ est apparu en premier sur Institut Imagine.