FUNDED PROJECTS

Atopic dermatitis (AD) is a chronic inflammatory disease affecting approximately 10-20% of the population worldwide. Over the past years, the pathogenesis of the disease has been found to result from a combination of functional defects including impaired epidermal barrier function, abnormal epidermal cell-cell adhesion and immune dysfunction. The role of dermal cells, and skin fibroblasts more specifically, in the pathogenesis of AD remains poorly understood. In the present project we aim to broaden our understanding of the role of the dermis (and fibroblasts) in AD.

The research program will be conducted along three sequential and inter-dependent phases:

(1) we will initially delineate gene and protein abnormal expression in fibroblasts in AD and inherited disorders featuring AD-like manifestations. To achieve this goal, we will use a combination of broad transcriptomic analysis, coupled with single-cell transcriptomic profiling of dermal cellular elements extracted from skin biopsies obtained from AD and AD-like inherited disorders patients and healthy controls. Data will be integrated using advanced bioinformatics tools;

2) we will then characterize the functional consequences of the genetic defects identified in the previous phase focusing on the effect of abnormal gene expression in AD fibroblasts on epidermal cell proliferation and differentiation; epidermal cell-cell adhesion; and immune function. This dermal-epidermal crosstalk in AD will be delineated through functional studies in vitro and in vivo using mice models;

(3) finally, based on data gleaned in phases 1 and 2, and small molecule high throughput screening, we will attempt at translating this new knowledge into novel therapeutic approaches for AD.
This research program is aimed to reveal a novel array of biomarkers and therapeutic targets based on a thorough delineation of the role of dermal elements in the pathogenesis of AD. This will likely pave the way for innovative management approaches to AD and related disorders.