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.
Skin barrier function is first line of defence – Epidermal T cells dynamic, interplay and function
Grantee: Charlotte Menné Bonefeld, Associated Professor, Department of Immunology and Microbiology, University of Copenhagen
Amount: DKK 2,385,900
Grant category: Research Grants in open competition
Year: 2016
Geography: Denmark
The skin provides the first barrier of defence between the body and the environment. It is one of the largest organs of the human body and is constantly being exposed to pathogens and environmental triggers.
The outermost layer of the skin is the epidermis and it consists of a variety of both immune and non-immune cell types. Among the immune cells within epidermis are the T cells. One of the important characteristics of T cells is that they can develop into memory T cells following their activation.
Experimental work is often done with mice, but experience shows that there is difference between T cells in humans and mice epidermis – a difference that until recently has been thought related to species diversity.
Recent findings, however, have shown that environmental triggering factors, such as microorganisms or chemical irritants, lead to a dynamic shaping of the type of T cells present in the epidermis. Based on these discoveries, the team led by Charlotte Menné Bonefeld has hypothesised that the difference between T cells in human and mice epidermis are not mediated by species differences, but rather by difference in skin exposure to microorganisms and chemicals that occurs early and throughout the whole life.
Therefore, the team will investigate i) the similarities and differences of T cells in human and mice epidermis, ii) the effect of allergen and infection agents on the phenotype and activity of epidermal T cells and iii) the interplay between epidermal immune cells forming the immunological barrier properties of the skin.
Answering these questions will be crucial for developing better treatments for inflammatory skin diseases as it is very likely that these mechanisms play a central role in the pathogenesis of several inflammatory skin diseases like allergic contact dermatitis, atopic dermatitis and psoriasis.
ICR Agonists as novel therapeutics for psoriasis treatment
Grantee: Vasileios Bekiaris, Ph.D., Associate Professor, Section for Immunology and Vaccinology, National Veterinary Institute, Danish Technical University
Amount: DKK 1,047,816
Grant category: Research Grants in open competition
Year: 2016
Geography: Denmark
Psoriasis and most autoimmune diseases are characterised by a deregulated hyper activation of T cells leading to chronic tissue destruction and in many cases significant morbidity. Immune checkpoint receptors (ICRs) negatively regulate the immune system by dampening lymphocyte functionality.
Bekiaris and his team have, as have others, shown that manipulation of these ICRs can alter the outcome of the immune response; a strategy currently successful in cancer immunotherapy.
In this project the team will use the mouse psoriasis-model (IMQ) to test the hypothesis that in vivo activation of specific ICRs will block the induction and progression of psoriasis. In addition, the team aims to characterise the importance of ICR signalling during the course of psoriasis, both at the cellular and molecular levels.
The study will delineate the molecular mechanisms underlying ICR signalling during skin inflammation and potentially create a new pathway for possible future treatment of psoriasis though opening of new targets.
Analysis of epigenetic control of IL-23 expression in keratinocytes
Grantee: Dr Cord Brakebusch, Professor, Section of Molecular Pathology, BRIC, Department of Biomedical Sciences, University of Copenhagen
Amount: DKK 2,140,000
Grant category: Research Grants in open competition
Year: 2016
Geography: Denmark
This study seeks new targets to reduce the formation of psoriatic lesions. A novel epigenetic mechanism, which is known to induce IL-23 in psoriasis, is also found in non-lesioned skin and may hold promise.
Psoriasis is a chronic inflammatory skin disease that involves a complex crosstalk between immune cells and skin cells (keratinocytes). While the etiology of psoriasis is basically unknown, many researchers have gauged the elements of this crosstalk – in many models. During this work, they have shown that there are multiple different, yet intertwining mechanisms underlying the disease.
One is that monoclonal antibodies that target the IL-23/IL-17 immune axis have demonstrated impressive clinical efficacy in patients with moderate-severe psoriasis. There are however, still many missing pieces of the puzzle to fully understand how this disease initiates and develops.
Dr Cord Brakebusch’s team has demonstrated that keratinocyte-derived IL-23 is sufficient to cause chronic skin inflammation in mice. Furthermore, they have elucidated an epigenetic mechanism which controls IL-23 expression and it is explained that the epigenetic control mechanism has been shown not just in active psoriasis lesions, but also, albeit to a lesser extent, in normal-appearing skin of psoriasis patients.
This suggests that the epigenetic alterations might precede the development of psoriasis lesions, and the team now wants to identify and validate targets for small molecule drugs that may prevent excessive IL-23 expression by keratinocytes through this epigenetic mechanism.
As a long-term goal for the study and its potential findings Dr Brakebusch and his team hope that topically administrated small molecular weight inhibitors could prevent excessive IL-23 production by keratinocytes – and ultimately aim at reducing the formation of psoriatic lesions.
International Project on the Global Epidemiology of Psoriasis: Development of the Global Psoriasis Atlas
Grantee: Darren Ashcroft, Professor of Pharmacoepidemiology, The University of Manchester, UK, Chris Griffiths, Professor of Dermatology, Head of Dermatology Research Centre, University of Manchester, UK, & Matthias Augustin, MD, Professor and Director, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg, Germany
Amount: DKK 6,370,000
Grant category: Research Grants in open competition
Year: 2016
Geography: Germany, United Kingdom
The LEO Foundation supports the project “International Project on the Global Epidemiology of Psoriasis: Development of the Global Psoriasis Atlas”.
The atlas (GPA) will be a seminal work with focus on epidemiological research that will allow researchers and medical practitioners to compare incidence and prevalence of psoriasis between populations in different countries and thus yield a global ‘picture’ of the disease burden of psoriasis
The work with the GPA is done in a project group with three of the world’s leading international dermatology organisations: International League of Dermatological Societies (ILDS), a global organisation representing 148 dermatological societies worldwide; International Psoriasis Council (IPC), a not-for-profit organisation comprising leading international psoriasis experts dedicated to advancing knowledge about psoriasis and enhancing care of the disease; and the International Federation of Psoriasis Associations (IFPA), a not-for-profit organisation representing psoriasis patients worldwide.
The mission of the GPA is to provide the common benchmark on the complete burden of psoriasis in all countries and regions throughout the world. The GPA will leverage existing data from publications and registries – and additional studies will be commissioned when gaps are identified.
The GPA is a long-term project that seeks to drive continuous improvement in the understanding of psoriasis and to uncover how it affects both the individual and society at large – and will as such play an important part of the overall quest to support research that will someday help researchers find a cause and a cure for psoriasis.
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.
Big Bang – support for Denmark’s largest science conference
Grantee: Astra, the national Centre for Learning in Science, Technology and Health in Denmark, Copenhagen
Amount: DKK 2,000,000
Grant category: Education and Awareness Grants
Year: 2016
Geography: Denmark
Denmark’s largest science conference, the Big Bang Conference, has received two million Danish kroner over the next three years from the LEO Foundation.
Big Bang is the largest Danish science conference and exhibition targeted all who teaches, facilitates or researches in the science and science fields – in primary and secondary schools and higher education.
The conference, held once a year, gathers more than 1,000 people for two involving and inspiring days with relevant keynote speakers, a humming exhibition atmosphere, involving workshops and novel ideas for the continued renewal of science education.
The conference is held next on 23 and 24th March 2017 in Odense Congress Center, Denmark.
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.