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.

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.

www.bigbangkonferencen.dk

Young Scientists

Grantee: Mikkel Bohm, Young Scientists (Astra)

Amount: DKK 3,000,000

Grant category: Research grants in open competition

Year: 2015

Geography: Denmark

The talent competition, Young Scientists, is developing talents in both kids and young people in science.

It is believed that science is a powerful tool to understand and change the world for the better. The competition’s aim is to contribute to society in a meaningful way by inspiring a new generation and giving them engaging experiences with science.

The LEO Foundation has found this work important and supports the competition over three years.

LEO Foundation Center for Cutaneous Drug Delivery

Grantee: Department of Pharmacy, University of Copenhagen

Amount: DKK 40,000,000

Grant category: Strategic grants

Year: 2015

Geography: Denmark

Understanding how drugs interact with skin has long been a challenge within pharmaceutical research. Now, a new center at the Department of Pharmacy, UCPH, is set to become an international lighthouse in this research area, supported by a DKK 40 million grant from the LEO Foundation.

The LEO Foundation Center for Cutaneous Drug Delivery will form the basis of new research on skin and drugs. Behind the project is the Department of Pharmacy at the University of Copenhagen, where the center will also be located. The Director of the new center, Martin Malmsten, was formerly Head of Research at Uppsala University.

“I hope to contribute with my experience and thus help motivate and inspire colleagues and employees, enabling us to provide the best possible results. At the same time, I look forward to becoming part of the University of Copenhagen, where they have been very willing to prioritize strategic focus areas. The new center offers great and long-term opportunities for making an impact on international research and I’m happy to be part of this initiative, which will lift research in a very exciting area,” said Martin Malmsten.

The LEO Foundation Center for Cutaneous Drug Delivery will conduct research on what happens in and on the skin when we apply drugs. There will be a particular focus on the physical-chemical aspects of the interaction between skin and drugs, which is important to the development of new drugs. This will hopefully help optimize the drug properties and allow for maximum utilization while simultaneously minimizing side effects.

“Our new center meets a huge demand for understanding how drugs interact with skin. With a strong team of highly qualified researchers, we will set new standards for research in the field of dermatology and I’m both proud and grateful that this grant from the LEO Foundation has helped us attract new and strong forces to UCPH. This new strategic effort will benefit patients as well as society in general,” said Dean Ulla Wewer from the Department of Health and Medical Sciences at the University of Copenhagen.

Generating new knowledge while also providing a space for innovative research methods and new analytical technologies is what the center aims for. The LEO Foundation has backed the center with a grant of DKK 40 million over the next ten years, which in itself is quite remarkable.

“We’re very happy to support this important initiative and the grant of DKK 40 million over the next ten years is the single largest grant the foundation has ever awarded. What’s more important, however, is the fact that we are quite convinced that the center with its strong team of researchers has the potential to become a global powerhouse in terms of research on the dynamic interaction between drugs and skin,” said Lars Olsen, Chairman of the LEO Foundation.

The LEO Foundation Award 2014 – Gold Award

Grantee: Dr. Kim B. Jensen

Amount: DKK 1,000,000

Grant category: LEO Foundation Awards

Year: 2014

Geography: Denmark

Presented to Ph.D. Kim B. Jensen, associate professor at the Biotech Research and Innovation Centre at the University of Copenhagen.

Dr. Jensen’s research focuses on how the epidermis, the outer layer of the skin, is constantly renewed throughout life in an organised manner by epidermal stem cells. Epidermal stem cells need to be carefully controlled as any imbalance is likely to have devastating consequences. Too little contribution from the stem cells can lead to bleeding ulcers, whereas too much contribution can lead to skin cancer. By examining how stem cells are regulated in the epidermis, Jensen hopes to gain insights into mechanisms responsible for disease development and identify new drugable pathways.

Psoriasis in children

Grantee: Professor Lone Skov, Department of Dermato-Allergology, Gentofte Hospital

Amount: DKK 4,500,000

Grant category: Research grants in open competition

Year: 2014

Geography: Denmark

Psoriasis is a chronic inflammatory skin condition with a prevalence of 2-3% in northern Europe. While considerable research exists on adults with psoriasis, there is little research on the condition in children. Identifying key factors associated with psoriasis in childhood may lead to more effective control and possibly even prevention of the condition.

The study aims to determine environmental and genetic risk factors relating to the development of psoriasis in children, the nature of stress related to the child and family, and quality of life. The project also aims to determine the link with risk factors of co-morbidity and the effect of early intensive treatment.

The study is led by Professor Lone Skov, Department of Dermato-Allergology, Gentofte Hospital, Denmark. The team will explore the following hypotheses:

  • Risk factors for early onset of psoriasis can be predicted
  • Early debut of psoriasis has a significant impact on quality of life and individual and family-related stress
  • Early intensive treatment leads to remission
  • There is already an increased risk of co-morbidity in children with psoriasis
  • Age at debut, risk factors and co-morbidity are related
    to the genetic risk.

The study offers a unique possibility to access data from children with psoriasis shortly after diagnosis, which in turn can pave the way for new and improved tools for assessing the impact of the condition on quality of life in a well-controlled study design.

Psoriasis and cardiovascular co-morbidity – epidemiological and experimental studies

Grantee: Dr Peter Riis Hansen, Department of Cardiology P, Gentofte Hospital

Amount: DKK 4,200,000

Grant category: Research grants in open competition

Year: 2012

Geography: Denmark

Psoriasis patients have increased risk of cardiovascular disease (CVD), which still carries high morbidity and mortality in western societies, and is increasing dramatically in the emerging economies.

Consequently, research directed at the interface between psoriasis and CVD, from the level of epidemiological studies to basic experimental research, is of paramount importance in order to improve overall care for psoriasis patients, as well as supporting the need to seek help to receive treatment.

A research project led by Dr Peter Riis Hansen, Gentofte Hospital, Department of Cardiology P, Denmark, will help to:

  • Inform and motivate dermatologists to play a pivotal role in screening and helping patients with psoriasis to prevent an increased risk of CVD
  • Motivate patients with psoriasis to, firstly, seek treatment and assessment of their CVD risk and, secondly, improve treatment of psoriasis to reduce the overall immune activation
  • Establish a murine model of psoriasis and CVD that is suitable for mechanistic studies and preclinical drug evaluation
  • Identify new markers of psoriasis and/or CVD activity that may be relevant for clinical use.

Publications:

Khalid U et al. Psoriasis and new-onset diabetes: a Danish nationwide cohort study. Diabetes Care 2013;6:2404-7

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714512/

Khalid U et al. Psoriasis and risk of heart failure: a nation-wide cohort study. Eur J Heart Fail 2014;16:743-8

http://www.ncbi.nlm.nih.gov/pubmed/24903077

Khalid U et al. Sarcoidosis in patients with psoriasis: a population-based cohort study. PLoS ONE 2014;9(10)e109632

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186869

Khalid U et al. Increased risk of aortic valve stenosis in patients with psoriasis: A nation-wide cohort study. Eur Heart J 2015;36:2177-83

http://eurheartj.oxfordjournals.org/content/36/32/2177.long

Khalid U et al. A nationwide study of the risk of abdominal aortic aneurysms in patients with psoriasis

http://atvb.ahajournals.org/content/36/5/1043.long

Madsen M et al. Effects of TPA-induced experimental psoriasis-like skin inflammation in atherosclerosis-prone apoE knock-out mice. BMC Dermatology 2015

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940745

Epidemiology of eczema disease in Denmark

Grantee: Professor Torkil Menné and Professor Jeanne Duus Johansen, Gentofte Hospital

Amount: DKK 2,828,000

Grant category: Research grants in open competition

Year: 2012

Geography: Denmark

The project involves several research groups at Gentofte Hospital in Copenhagen and is headed by Professor Torkil Menné and Professor Jeanne Duus Johansen.

The work aims to shed more light on the incidence of eczema in the general population and pave the way for improved prevention and treatment.

Eczema is the most prevalent of the skin disorders. It is not only one of the most common childhood diseases, but also a typical occupational disease, making it one of the most widespread diseases in the overall population. Eczema also results in substantial costs and loss of quality of life for patients.

Despite the disease prevalence, there is a shortage of data and research on eczema in the general population.

This project, which draws on a number of databases and disease registries unique to Denmark, aims to produce a detailed picture of the clinical and sociodemographic aspects of eczema in both the general population and the patient population.

Its specific aims are:

  • To describe the consequences of eczema in terms of health care, education and employment, and the development of co-morbidities
  • To explore the genetics behind eczema and its
    consequences.

Publications:

Anatomical patterns of dermatitis in adult filaggrin mutation carriers

J Am Acad Dermatol. 2015 Mar;72(3):440-8. doi: 10.1016/j.jaad.2015.01.001. Epub 2015 Feb 7

Predictive factors of self-reported hand eczema in adult Danes – a population based cohort study with 5 year follow-up

Br J Dermatol. 2016 Aug;175(2):287-95. doi: 10.1111/bjd.14476. Epub 2016 May 24

Health-related quality of life in adult dermatitis patients stratified by filaggrin genotype

Contact Dermatitis. 2017 Mar;76(3): 167-177. doi: 10.1111/cod.12731. Epub 2016 Dec 16 

Hand eczema, atopic dermatitis and filaggrin mutations in adult Danes: a registry-based study assessing risk of disability pension

Contact Dermatitis. 2017 Aug;77(2):95-105. doi: 10.1111/cod.12786. Epub 2017 Apr 20

The LEO Foundation Scholarship for Dermatological Research

Grantee: Scholarship programme

Amount: DKK 2,200,000

Grant category: Research grants in open competition

Year: 2012

Geography: Australia, Denmark

The LEO Foundation Scholarship for Dermatological Research aims to strengthen research collaboration within the field of skin cancer between Australia and Denmark by supporting training of and research by young scientists.

One scholarship is offered annually on behalf of the LEO Foundation, alternating between Australia and Denmark.

A candidate from Australia travels to work within a Danish tertiary institution and a Danish student is selected with a view to joining an Australian campus.

The funds received may be used as part of an ongoing PhD project or for postdoctoral research. The funds must in part support a research/educational stay in Australia of at least six months for the Danish student.

Publications

Automated detection of actinic keratoses in clinical photographs

Hames SC, Sinnya S, Tan JM, Morze C, Sahebian A, Soyer HP, Prow TW.

PLoS One. 2015 Jan 23;10(1):e0112447. doi: 10.1371/journal.pone.0112447. eCollection 2015

Counting actinic keratosis – is photographic assessment a reliable alternative to physical examinations in clinical trials?

Sinnya S, O’Rourke P, Ballard E, Tan JM, Morze C, Sahebian A, Hames SC, Prow TW, Green AC, Soyer HP.

Acta Derm Venerol. 2015 May;95(5):604-5. doi: 10.2340/00015555-2040. No abstract avaliable

The future of keratinocyte skin cancer surveillance: automated image analysis to identify and monitor keratinocyte dysplasia

Hames SC, Prow TW.

Curr Probl Dermatol. 2015;46:77-84. doi: 10.1159/000366540. Epub 2014 Dec 18

Automated segmentation of skin strata in reflectance confocal microscopy depth stacks

Hames SC, Ardigò M, Soyer HP, Bradley AP, Prow TW.

PLoS One. 2016 Apr 18;11(4):e10153208. doi: 10.1371/journal.pone.0153208. eCollection 2016.

Automated detection of actinic keratoses in clinical photographs

Hames SC, Sinnya S, Tan JM, Morze C, Sahebian A, Soyer HP, Prow TW.

PLoS One. 2015 Jan 23;10(1):e0112447. doi: 10.1371/journal.pone.0112447. eCollection 2015.

Counting actinic keratosis – is photographic assessment a reliable alternative to physical examination in clinical trials?

Sinnya S, O’Rourke P, Ballard E, Tan JM, Morze C, Sahebian A, Hames SC, Prow TW, Green AC, Soyer HP.

Acta Derm Venereol. 2015 May;95(5):604-5. doi: 10.2340/00015555-2040. No abstract available.

The future of keratinocyte skin cancer surveillance: automated image analysis to identify and monitor keratinocyte dysplasia

Hames SC, Prow TW.

Curr Probl Dermatol. 2015;46:77-84. doi: 10.1159/000366540. Epub 2014 Dec 18

Anatomical skin segmentation in reflectance confocal microscopy with weak labels*

Hames SC, Ardigò M, Soyer HP, Bradley AP, Prow TW.

http://ieeexplore.ieee.org/xpls/abs_aa.jsp?arnumber=7371231&tag=1

* This won the Canon Extreme Imaging Competition (DICTA category) prize in late 2015

The LEO Foundation Award 2011 – Silver Award

Grantee: Dr. Charlotte Menné Bonefeld

Amount: DKK 500,000

Grant category: LEO Foundation Awards

Year: 2011

Geography: Denmark

Presented to Dr. Charlotte Menné Bonefeld, a Danish immunologist with a strong interest in dermatological research.

Despite her young age, Dr. Bonefeld has already made a significant contribution to the field of dermatology. Her research achievements include novel promising findings showing down-regulation of the immune system (a process known as tolerance) when an individual is exposed repeatedly to strong allergens such as those present in hair dyes. These results give great perspectives in finding new treatments and, equally important, give novel insight into why some people become allergic and some do not.