Defining the epigenetics of rosacea
Grantee: Luis Garza, Department of Dermatology, Johns Hopkins School of Medicine, Baltimore, MD
Amount: DKK 330,000
Grant category: Research Grants in open competition
Year: 2016
Geography: USA
Rosacea affects many people around the globe and treatments could be better and more efficient. Defining new possible treatments will not only satisfy this clinical need, but also offer the opportunity to learn about the pathogenesis of rosacea and subsequent basic knowledge about skin biology.
The discovery of the role of the innate immunity in rosacea has generated many interesting new avenues for investigation.
The team led by Luis Garza points to the fundamental role of keratinocytes in disease pathogenesis as a critical insight given that keratinocytes, more than fibroblasts for example, contribute to innate immunity pathways.
This, they say, begs an interesting question: if keratinocyte turnover is so rapid such that entirely new cells are present every several months, how is the propensity for rosacea so robustly inherited from ‘mother’ to ‘daughter’ keratinocyte?
The team hypothesises that epigenetic lesions are more likely to explain the mostly adulthood acquisition of rosacea and the stability of disease in adulthood rather than DNA mutations. With this project, the team has the potential to generate data that can be used in academics and industry to measure improvements and severity of rosacea through its epigenetic profile.
LEO Foundation SPARK grants at Stanford
Grantee: Kevin Grimes, Director, SPARK Programme, Associate Professor, Chemical and Systems Biology, Stanford University, California
Amount: DKK 4,500,000
Grant category: Research Grants in open competition
Year: 2016
Geography: USA
Bridging the gap between early research and clinical development is a challenging endeavour. There is an inherent risk that early-stage programs will fail during development, no matter how promising the science is.
Such nascent programs are unlikely to attract interest from industry until they have reached significant milestones, and very little funding is available from the NIH, foundations, or private enterprise for this critical transition.
The LEO Foundation SPARK donations at Stanford will help incubate and accelerate dermatology projects. SPARK is a unique partnership between university and industry targeted advancement of Stanford research towards development of new breakthrough therapies. SPARK provides access to specialised knowledge and technical expertise regarding drug and diagnostic development, dedicated core laboratory facilities, and sources of funding to support translational efforts.
The donations will be awarded as a supplement to the existing suite of support and funding from Stanford and will ensure that as many as 15 Stanford dermatology projects will be progressed towards human proof of concept.
It is expected that the grant will foster a renewed and unique focus on dermatology at Stanford University and enable a larger number of orphan drug research projects to reach actual clinical development.
The grant from the LEO Foundation is paid out in three equal portions in 2016, 2017 and 2018.
Learn more about the SPARK Program at Stanford University here.
Epithelial Differentiation and Keratinization Gordon Research Conference (GRC) and Gordon Research Seminar (GRS)
Grantee: Prof. Catharina (Carien) Maria Niessen, Department of Dermatology, University of Cologne, Germany; and Brenda Figueroa, Gordon Research Conferences, West Kingston, Rhode Island, USA
Amount: DKK 149,099
Grant category: Research Grants in open competition
Year: 2016
Geography: Germany, USA
The 2017 Gordon Research Conference on Epithelial Differentiation and Keratinization (GRC-EDK), to be held May 6-12 in Italy, is the premier international meeting in epithelial biology.
It has been held biennially since 1979 with attendance from leading epithelial biology researchers, leaders from other fields, and early career scientists with innovative and exciting research programs to present and promote the latest conceptual, translational and technological advances in epithelial biology.
Today, the meetings take on stem cell biology, regenerative medicine, inflammatory skin diseases, skin cancer, epigenetics, and global genomics, and the program moreover explores developments in gene therapy, genome organisation, cell competition, stress responses as well as cutting edge advances in intravital imaging.
A third of the speakers are from outside the area in order to fuel new concepts and promote discussion of novel ideas, and more than a third of the oral presentations come from submitted abstracts to accommodate late breaking exciting stories and ensure speaking opportunities for young investigators.
To promote collaboration between academic medicine and industry the meeting also invites speakers from biotech and other academic scientists with strong industrial ties. Finally, the meeting will continue the commitment to trainee mentorship, including a career mentoring panel discussion with special emphases on careers in academia versus industry, and the importance of diversity within science.
Full thickness skin models from human pluripotent stem cells for identification and testing effectiveness of personalised therapies in atopic dermatitis
Grantee: Dr Dusko Ilic, MD, PhD, Reader in Stem Cell Sciences, Kings College London, Dr Reiko Tanaka, Lecturer, Department of Bioengineering, Imperial College, London, Dr Patrick Harrison, Senior Lecturer, Department of Physiology, University College Cork, Ireland, and Professor Theodora Mauro, MD, Professor of Dermatology, San Francisco Veterans Affairs Medical Center, USA
Amount: DKK 9,980,000
Grant category: Research Grants in open competition
Year: 2016
Geography: Ireland, United Kingdom, USA
This is an exciting project that, with the international group’s extensive research and know-how in mind, has the potential to create an intriguing base for novel personalised treatments for atopic dermatitis (AD). The project moreover holds an innovation potential that may make it stand out in the emerging global bio-economy.
The prevalence of AD, an inflammatory skin disease resulting in itchy, red, swollen and cracked skin, is constantly increasing. Today, it affects 15-30 percent children and 2-10 percent adults worldwide, presenting a significant economic burden to healthcare systems.
There is no cure for AD, only soothing of the symptoms. In the majority of AD patients, the disease is a consequence of a blend of genetic defects of the skin barrier defects and abnormal immune responses influenced by environmental factors.
Until now, the models used to assess the interplay are not particularly predictive. The group behind this project aims to change this by using the latest advances in stem cell science, gene editing and tissue engineering to develop and validate innovative 3D in vitro models of skin – making the models similar to skin in AD patients by emulating full thickness skin of varying barrier integrity; faulty, partially repaired or intact, and immune response composition.
As part of the project, the group will also develop mathematical computer models to accurately address the predictive, prognostic and therapeutic outcome of personalised AD therapy – in order to address co-dependence of the quantitative and qualitative changes in skin barrier and activation of immune cells.
The 3D models will also be made available to test various novel therapeutic approaches for AD treatment in a patient specific manner.
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