Melanocyte stress response pathways and their role in the onset of vitiligo
Grantee: Prashiela Manga, PhD , Associate Professor Dermatology and Cell Biology, New York University School of Medicine
Amount: DKK 5,037,192
Grant category: Research Grants in open competition
Year: 2016
Geography: USA
Vitiligo, an acquired skin disease in which pigment cells, melanocytes, are destroyed, affects 1-2% of people worldwide. The disease deprives the skin of photoprotection leaving it more susceptible to solar damage and compromised cutaneous immunity – and the disease impacts physical and mental health.
Vitiligo is thought to occur in genetically susceptible individuals after being exposed to environmental triggers. Some individuals develop contact vitiligo after direct exposure to certain chemicals. As disease progression in vitiligo is independent from initiating factors, this subset of individuals makes it possible to study vitiligo at large.
The hypothesis in this project is that melanocytes from healthy individuals can withstand exposure to triggers by initiating a stress response regimen that allows the cell to return to homeostasis. These pathways may be disrupted in individuals who develop vitiligo, leaving melanocytes stressed following challenge, causing them to be targeted for removal by the immune system.
In order to investigate this hypothesis, the project will investigate survival pathways in melanocytes cultured from biopsies taken from pigmented skin from individuals who have developed vitiligo.
International Eczema Council
Grantee: Amy Paller, MS, MD, IEC President, Professor of Dermatology and Professor of Pediatrics, Northwestern University’s Feinberg School of Medicine, Chicago, and Emma Guttman-Yassky, MD, PhD, IEC President-Elect, Associate Professor of Dermatology & Immunology, Department of Dermatology, Icahn School of Medicine, Mount Sinai, New York
Amount: DKK 340,000
Grant category: Research Grants in open competition
Year: 2016
Geography: USA
The IEC is convening a meeting at the ESDR in September 2015 to write a position paper on Atopic Dermatitis as a systemic disease.
In March 2016, the IEC will hold a session at the Annual AAD in Washington, D.C. focusing on AD phenotyping – starting to use biomarkers to assess subgroups of AD, which may be relevant to the understanding of disease and treatment decision-making.
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:
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
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
Phenotyping itch in atopic eczema and psoriasis patients
Grantee: Dr Gil Yosipovitch, MD, Professor of the Department of Dermatology at Wake Forest School of Medicine, Winston-Salem, North Carolina
Amount: EUR 264,874
Grant category: Research Grants in open competition
Year: 2012
Geography: USA
The LEO Foundation is supporting another project that investigates
itching and may also pave the way for new anti-itch treatments.
The study is led by Dr Gil Yosipovitch, MD, Professor of the Department of Dermatology at Wake Forest School of Medicine, Winston-Salem, North Carolina, USA, and seeks to investigate aspects of itching in patients with atopic dermatitis and psoriasis.
Itching affects millions of people worldwide and represents a significant medical challenge as no mechanism-specific treatments are currently available. The genetic aspects of itching in chronic pruritic conditions such as atopic dermatitis and psoriasis are also rather under-investigated.
Dr Gil Yosipovitch will examine the expression of genes, neuropeptides and other itch-specific mediators specifically implicated in atopic dermatitis and psoriasis in comparison to healthy controls.
The exploration of this area may hold good news for patients, as the findings may be useful in developing new anti-itch treatments.
Publication
The genetics of chronic itch: gene expression in the skin of atopic dermatitis and psoriasis patients with severe itch
* Nattkemper LA, Tey HL, Valdes-Rodriguez R, Lee H, Mollanazar NK, Albornoz C, Sanders KM, Yosipovitch G, The genetics of chronic itch: gene expression in the skin of atopic dermatitis and psoriasis patients with severe itch, The Journal of Investigative Dermatology (2018), doi: 10.1016/j.jid.2017.12.029.
See article (pdf): Genetics of Chr Itch