Identification and Characterization of Key Itch Mediators and Receptors in Human Pruitus

Grantee: Professor Martin Steinhoff, University of California San Francisco

Amount: USD 388,225

Grant category: Research grants in open competition

Year: 2013

Geography: USA

Itch is probably the most common symptom in dermatology and it is associated with a significant impact on the patient’s life.

A team led by Professor Martin Steinhoff, University of California San Francisco, has set out to develop novel targeted therapies for chronic itch in humans.

Besides the lesional and non-lesional as compared to healthy skin, the project team will also identify critical itch mediators and/or receptors that are expressed (and activated) in human dorsal root ganglion (DRG) and spinal cord tissue. To address this, mediators will be identified as well as receptors associated with human itch, and thereby the team will be able to define “biomarkers” for the different pruritic human diseases.

The project will be the first-of-a-kind study to analyse the expression and distribution of key itch mediators and receptors in human skin, human DRG and human spinal cord, and will therefore provide a significant basis for future translational research that targets these mediators/receptors in the different subtypes of itch.

Moreover, it is the first time that it will be tested whether several new itch pathways that have been described in murine skin models are relevant, i.e. can be translated, in human disease state.

Defining the skin and blood biomarkers of pediatric atopic dermatitis

Grantee: Dr. Emma Guttman, MD, PhD, Associate Professor of Dermatology, Director Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine, Mount Sinai, New York

Amount: USD 1,046,400

Grant category: Research grants in open competition

Year: 2013

Geography: USA

Despite considerable impact on quality of life, atopic dermatitis, or eczema, has not been studied extensively in children although as many as one in five experience the condition. Atopic dermatitis, or eczema, is a chronic skin condition, characterised by itching and inflammation, and frequently occurs in people who have other allergic conditions, such as asthma and hay fever.

Dr. Guttman has set out to define the skin and blood biomarkers of atopic dermatitis in children. She and her team will investigate how skin biomarkers compare to disease activity, epidermal barrier function and known biomarkers in adults with atopic dermatitis. They will also investigate whether blood biomarkers could offer a less invasive way to monitor skin changes than a skin biopsy, which can be difficult to perform in children.

With better knowledge of what causes atopic dermatitis in children, the researchers hope to develop more targeted therapies for the disorder as well as for other atopic conditions, such as asthma and hay fever. Together, these three disorders form an “atopic triad”.

Publications:

Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets

J Allergy Clin Immunol. 2015 Oct; 136(4): 941–951.e3.

Early-Onset Pediatric Atopic Dermatitis Is TH2 but Also TH17 Polarized in Skin

J Allergy Clin Immunol 138 (6), 1639-1651. 2016 Sep 23.

Alterations in B-cell subsets in pediatric patients with early atopic dermatitis

J Allergy Clin Immunol. 2016 Dec 10 pii: S0091-6749(16)31452-X

Accelerated T-cell activation and differentiation of polar subsets characterizes early atopic dermatitis development

J Allergy Clin Immunol. 2016 Nov;138(5):1473-1477.e5

An IL-17-dominant immune profile is shared across the major orphan forms of ichthyosis.

J Allergy Clin Immunol. 2017 Jan;139(1):152-165