CV Science

Amandine Viau Cilia-dependent inflammatory signaling in homeostasis and response to injury

Course and current status

EDUCATION

2023 Habilitation à diriger des recherches (HDR)

Paris Cité University, Paris, France

2004-2009 PhD thesis in Physiology

Speciality: Biology and Pathology of Epithelia

Denis Diderot University, Paris, France

2002-2004 Master of Science in Biology and Pathology of Epithelia

Denis Diderot University, Paris, France

Master of Science in Genetics

Denis Diderot University, Paris, France

2000-2002     Bachelor of Science in Cell Biology and Pathophysiology

Pierre et Marie Curie & Denis Diderot Universities, Paris, France

RESEARCH EXPERIENCES

Since 2026   Principal Investigator

INSERM U1163, Institut IMAGINE, Paris, France

Cilia-dependent inflammatory signaling in homeostasis and response to injury

Since 2022   CRCN INSERM (Researcher)

INSERM U1163, Institut IMAGINE, Paris, France

Role of cilia inflammatory signaling in kidney diseases and response to bacteria.

2019-2022     Post-doctoral research

INSERM U1163, Institut IMAGINE, Sophie Saunier’s lab, Paris, France

Molecular mechanisms of juvenile nephronophthisis.

2016-2018     Post-doctoral research

INSERM U1151, INEM, Fabiola Terzi’s lab, Necker Hospital, Paris, France

Control of kidney inflammation by primary cilia.

2012-2016     Post-doctoral research

Zentrale Klinische Forschung, Division of Nephrology, University Hospital Freiburg, Gerd Walz’s lab, Kühn’s team, Freiburg im Breisgau, Germany

Crosstalk between polycystins and mTOR signaling pathway in primary cilia microenvironment.

2010-2011     Post-doctoral research

INSERM U845, Growth & Signaling Research Center, Fabiola Terzi’s lab, Necker Hospital, Paris, France

Biochemical and functional characterization of Lipocalin 2 in mouse and human chronic kidney disease.

2004-2009     PhD thesis

INSERM U845, Growth & Signaling Research Center, Necker Hospital, Paris, France

Supervisor: Fabiola Terzi, MD-PhD

Role of Lipocalin 2 during progression of renal lesions in mouse and

human chronic kidney disease.

2003-2004    Master II laboratory training

Inserm U426, Bichat Hospital, Paris, France

Supervisor: Fabiola Terzi, MD-PhD

Identification of new mediators involved in the progression of renal lesions in chronic kidney disease.

2003               Master I laboratory training (5 months) 

Dipartimento di Biologia, Università degli Studi di Padova, Padova, Italy

Supervisors: Francesco Argenton, PhD and Rodolfo Costa, PhD

Characterization of Timeless 2 gene expression in zebrafish development.

2002               Bachelor training (3 months) 

Inserm U574, Necker Hospital, Paris, France

Supervisor: Laurence Heidet, MD-PhD

Identification of a mutation within the COL4A5 gene in the inherited nephropathy, Alport syndrome.

Scientific summary

I received my doctoral degree in 2009 from Université de Paris Cité (France). During my PhD in Dr Fabiola Terzi lab, I demonstrated the deleterious role of lipocaline 2 (LCN2/NGAL) in the pathophysiology of chronic kidney disease in rodent models. I identified LCN2 as a biomarker likely to predict chronic kidney disease progression in human. By combining different mouse and cell models, I showed that albumin overload induces LCN2 by inducing endoplasmic reticulum (ER) stress in renal tubular cells. Pharmacological inhibition of ER stress or genetic invalidation of LCN2 slows the development of renal lesions and prolongs animal survival in mouse models of protein overload. In humans, I provided the first clinical confirmation of the therapeutic effect of pharmacological inhibition of ER stress on LCN2 expression.

Following up, I joined the lab of Pr Wolfgang Kühn lab (Freiburg, Germany) in 2012, and gained expertise in modelling renal ciliopathies in cells and murine models. Indeed, by inactivating LKB1 specifically in the distal part of the nephron in mice, I discovered that the renal phenotype of these mice recapitulated human nephronophthisis (NPH), a renal ciliopathy affecting children. I identified a new ciliary complex associating LKB1 with the main proteins mutated in NPH and ADPKD (autosomal dominant polycystic kidney disease, another renal ciliopathy affecting adults): NPHP1 and PKD1. I showed that this complex repressed the expression of CCL2 (MCP-1), a macrophage chemoattractant. I confirmed the relevance of this model: loss of the primary cilium prevents CCL2 induction, macrophage recruitment and cystic growth associated with PKD1 inactivation in mice. I, thus, provided the first demonstration that the primary cilium from kidney tubules controls communication between epithelial and immune cells.

I then returned to France in 2017, to carry out a second postdoctoral internship at the INEM (Paris, France), to characterize the molecular players governing communication between primary cilia and immune cells, focusing on the transcription factor STAT3. I was able to demonstrate that tubular invalidation of STAT3 prevents neither cyst formation nor kidney function decline in an orthologous mouse model of ADPKD. However, the loss of STAT3 induces a significant increase in the expression of pro-inflammatory chemokines and infiltration of the polycystic kidney by a large contingent of macrophages and T lymphocytes, without aggravating the cystic disease. These data call into question the theory of the role of STAT3 in ADPKD pathophysiology and demonstrate that tubular activation of STAT3 participates in the dialogue between renal tubular cells and immune cells, orchestrated by the primary cilium.

In 2019, I decided to join the Laboratory of Hereditary Kidney Diseases headed by Dr Sophie Saunier at IMAGINE Institute in Paris (France) to pursue my research on cilia functions in the regulation of kidney inflammation, focusing on NPH. I identified a specific set of pro-inflammatory cytokines increased in renal epithelial cells derived from the urine of NPH patients and kidneys of NPH mouse models. I clearly demonstrated that this cytokine signature was associated with specific infiltration of the human and rodent NPH kidneys by immune cells, particularly neutrophils. Thus, mutations in the components of the primary cilium responsible for NPH induce the activation of specific inflammatory signaling, suggesting that the primary cilium is a signalling platform governing paracrine communication between tubular and immune cells.

In 2022, I was appointed a permanent researcher position (CRCN) at INSERM. I now focused my work on elucidating the physiologic role of the primary cilium in the regulation of inflammation. I recently showed that the primary cilium is a sensor of danger molecules that can be released during kidney infection or obstruction. This led me to propose that mutations in the genes responsible for renal ciliopathies cause an inappropriate activation of pathways normally involved in the response to danger signals. Through the use of in vivo models of genetic and acquired kidney diseases complemented with in vitro studies and patient’s derived material, I promote translational research to ultimately develop new therapeutic targets.