Explore our grantees and awardees

Grant category: Research Grants in open competition

Year: 2023

Geography: Spain

Allergic contact dermatitis (ACD) is a frequent skin condition associated with significant loss of quality of life. Finding specific biomarkers has emerged as a relevant challenge to improve the diagnosis of patients and unravel therapeutic alternatives.

Recent findings have highlighted the existence of allergen-specific transcriptomic fingerprinting (i.e., genetic patterns that enable unambiguous identification of entities – here allergens). However, to date only a few studies have been performed comparing a wide range of different allergens.

In the proposed project, Ana Giménez-Arnau, along with colleague David Pesqué, plans to make a gene expression analysis of biopsies from patch-induced ACD by methylisothiazolinone, diazolidinyl urea, nickel, isoeugenol and 2-hydroxi-ethylemetacrylate. Specifically, Ana Giménez-Arnau and her team will evaluate the presence of allergen-specific genetic fingerprinting, if common biomarkers between allergens can be identified, if there are transcriptomic changes depending on the biopsy timing and finally, they will correlate the results with the characteristics and intensity of inflammatory infiltrates and the level allergic reaction of the patch-induced ACD.

This prospective investigation will be based on recruitment of patients with ACD to the indicated allergens and includes two single patch tests containing the standard commercialized allergen and one single patch test with petrolatum (positive control) to be applied on day 1. Two biopsies will be taken on day 3 (one from the petrolatum patch and one from the first allergen patch). The final biopsy will be taken on day 5 from the remaining allergen patch.

Collectively, the project will provide insights to the genetic characteristics of allergic contact dermatitis and may provide a foundation for identifying common or allergen-specific treatment targets.

Grant category: Research Grants in open competition

Year: 2022

Geography: Spain

This project led by Xavier Gasull, also Professor at the Neuroscience Institute of the University of Barcelona, seeks to investigate and validate the potential of a newly identified target molecule on sensory nerves of the skin for treatment of chronic itch.

Chronic itch is a very important problem for patients suffering from several dermatologic diseases such as psoriasis, atopic dermatitis, or dry skin. Constant skin scratching in response to itching may further worsen the skin lesion.

In all these dermatological conditions, pruritic (itching) stimuli activate specific sensory neurons in the skin that send the message to the brain, where the sensation of itch is perceived and trigger the scratching response. The recent description of the specific sensory neuron subpopulations involved in this process has started the elucidation of some of the neural mechanisms involved in itch signalling.

From recent RNA sequencing databases and the functional characterization of itch sensing neurons, Xavier and his team have identified a new pharmacological target that can be used to decrease neuronal activation and relieve itch sensation. They have also identified a candidate drug activating this pharmacological target, which shows positive results decreasing acute and chronic itch not mediated through histamine, for which no effective drugs exist to date.

The focus of this project is to validate this new target in different skin disease models that produce chronic itch. They will use computational methods to design new drugs against this target, synthesize and then test them for therapeutical purposes. The hope is to benefit patients suffering from chronic itch in different skin diseases and, if successful, will add new pharmacological regimes for treating chronic itch.

Grant category: Research Grants in open competition

Year: 2020

Geography: Spain

The 2021 Gordon Research Conference (GRC) on Epithelial Differentiation and Keratinization is the premier international meeting in epithelial biology.

The GRCs are known to promote intense interactions among the participants – who are experts in the field of the conference, leading to new knowledge, career mentoring, collaborations, and advancing as well as strengthening the field of the conference. This Gordon Research Conference will advance cutting-edge research in skin biology, promote translation of key findings to clinical practice, and further the careers of early stage investigators to maintain the highest level of innovation of this field in the future.

The LEO Foundation has previously provided support for the two previous Gordon Research Conferences.

Grant category: Research Grants in open competition

Year: 2019

Geography: Spain

Targeting ZEB1 in macrophages as a new therapeutic approach to psoriasis.

Psoriasis involves deregulation of the innate and adaptive immunities. The metabolism of T cells as well as of keratinocytes is altered in psoriasis. Metabolism also controls the immunogenic versus tolerogenic responses of macrophages through mechanisms still not fully understood.

Our preliminary data indicate that: 1) the transcription factor ZEB1 is downregulated in the skin of psoriatic patients and of mouse models of psoriasis as well as in the peripheral blood monocytes/macrophages of psoriatic patients; 2) ZEB1 expression in macrophages ameliorates psoriatic lesions in mice; 3) Mechanistically, ZEB1 regulates macrophage tolerogenic responses in psoriasis by inhibiting mitochondrial activity and reducing pro-inflammatory cytokines and ROS.

The project will investigate: 1) the molecular mechanisms by which ZEB1 modulates macrophage response in psoriasis; 2) the expression, role, and mechanism of action in psoriasis of the related factor ZEB2, which has opposing roles to ZEB1 in other contexts; 3) ZEB factors in macrophages as therapeutic targets in psoriasis.

Implementing this project will be impactful as it will explore a new pathogenic mechanism and inform the design of safer and more targeted therapies to improve the quality of life of psoriatic patients. The proposal is innovative both conceptually—proposing unexpected immunoregulatory roles for ZEB1/2—and methodologically—using unique mouse models and bridging macrophage biology, gene regulation, and metabolism.