Grantee: Julia Oh, Jackson Laboratory, Farmington, Connecticut, USA

Grant: 2,107,529 DKK

My vision is to use metagenomics to better predict patient responses to immunotherapy and rationally design microbial adjuvant cocktails and engineered microbes to improve therapeutic outcomes.

However, a central question is the role of the local microbiota vs. systemic effects in potentiating these immunotherapeutics. In skin cancer, we have been studying how the skin microbiome affects predisposition and progression. Specific gut microbes have been implicated in the outcomes for immunotherapy response in melanoma skin cancer, supporting a role of systemic immune interactions via the gut in potentiating immunotherapy response.

However, because many aspects of cutaneous immunity are compartmentalized from systemic immune effects, we hypothesize that the skin microbiome could uniquely impact skin cancer outcomes during immunotherapy by modulating the cutaneous immune milieu.

Grantee: Patrick M. Brunner, Medical University of Vienna, Austria

Grant: 2,920,541 DKK

Atopic dermatitis (AD), the most common chronic inflammatory skin disease, typically starts very early in life.

While many patients outgrow their disease, some develop chronic disease for the rest of their lives. Mechanisms responsible, however, are completely unknown, and no biomarker exists that can predict the course of the disease.

Thus, we want to compare skin from young adults that have outgrown their AD, with skin from patients with active disease (namely normal appearing AD under topical glucocorticoid treatment, which can be expected to flare up again after cessation of treatment, thus harbouring a “disease memory”).

Skin from healthy control subjects will serve as baseline comparators. Due to low immune cell numbers in this type of tissue, we want to use in vivo suction blistering of AD patients to obtain (i) skin resident immune cells and (ii) skin proteins. Suction blister fluid will be analysed with low cytometry and single cell RNAseq (for cells) as well as a proteomic multiplex assays (OLINK) for soluble proteins. The blister roof (i.e. the epidermis) will also be harvested, and keratinocytes will be stored in liquid nitrogen for functional experiments.

Results obtained from flow cytometry, single cell RNAseq and proteomic approaches will then be used for such functional in vitro experiments (e.g. co-culturing, skin equivalents, stimulation experiments) in future research projects.

Overall, we hope that the identification of cellular and/or molecular factors influencing the natural course of AD could possibly identify targets for novel therapeutic approaches in AD, that could induce long term remission – or even lead to a cure – of AD.

 

Grantee: Sunny Y. Wong, Assistant Professor, University of Michigan, Ann Arbor, USA

Grant: 2,486,354 DKK

Basal cell carcinoma (BCC) is the world’s most common cancer and is defined by uncontrolled activation of the Hedgehog (Hh) signaling pathway.

Although previous studies have suggested that elevated Hh may be sufficient for BCC formation, mutations in the Notch pathway are also commonly observed. Furthermore, Notch-deficient mice are susceptible to forming BCCs, and our recent studies have shown that Notch can modulate tumor-drug response.

These studies seek to understand whether Notch affects multiple aspects of BCC tumorigenesis. Using a combination of animal studies and human BCC specimens, we will investigate how Notch modulates tumor progression and stem cell origin.

We will also model in mice a recent clinical trial, where Alzheimer’s patients treated with a Notch inhibitor reported increased incidence of BCC. We hypothesize that Notch may suppress tumorigenesis at multiple levels by controlling cell differentiation, apoptosis and turnover, similar to its function in normal skin and hair follicles.

These studies will ultimately build on the novel premise that BCCs may originate from a precursor lesion. Given that Notch mutations are the most commonly observed genetic aberrations in human skin, a deeper understanding of the tumor suppressive properties of this pathway is urgently needed.

Grantee: Svante Lindeburg, Golden Days, Denmark

Grant: 500,000 DKK

Bloom – at the core:

Bloom is an innovative festival about science and nature, which enlighten us on the Universe, the World and Ourselves. Framed in the lush Søndermarken at Frederiksberg in the heart of the capital city of Denmark, where some of the World’s greatest scientists, poets and philosophers have found inspiration through history, Bloom emerges each Spring as a sensual, experimental and thought-provoking festival version of natural sciences.

Prepared and communicated by some of the brightest scientists, thinkers, and artists of our time from here and abroad. By uniting the best from the world of festivals with the best from the scientific world, Bloom arm wrestles with Life’s greatest questions and over two days invite the audience to debates, talks, laboratories, conversations and nature walks under open skies.

Grantee: Henrik Wegener, University of Copenhagen, Denmark

Grant: 250,000,000 DKK

Diseases of the skin affect a quarter of the population, more than a billion people, at any given time. Despite impressive progress, especially in the area of immunology in skin diseases, the pace of innovation is not sufficiently high and new treatments are slow to reach patients.

Here, we propose to create a LEO Foundation Skin Immunology Research Center (Skin Immunology Center) that will become a beacon for skin research in Denmark and worldwide.

The Center will identify key questions relating to disease heterogeneity, new pathological mechanisms, and novel therapies of inflammatory skin diseases. With the ultimate aim of helping people with skin diseases in the best possible way, we will launch a focused effort employing cutting edge technologies to advance biological insights and translate basic discoveries to ‘proof of principle’ and then to ‘first in man’ applications (‘bench-to-bedside’). Importantly, observations and questions arising in the clinic will be taken back to the laboratory (‘bedside-tobench’). This team science concept and ecosystem with seamless translation and back-translation between basic biology and the clinic will animate the spirit of the Center from day one.

The Skin Immunology Center will be headquartered at the 12th floor of the Mærsk Tower, the new flagship building at the Faculty of Health and Medical Sciences, University of Copenhagen.

We will bring together the immunology of the skin, its diseases and comorbidities, ‘omics’ technologies, experimental models, and strong clinical integration to develop new stratification paradigms and therapies towards precision medicine. People will form the basis of the success of the Center and we will both empower existing scientists and strategically hire new talent. We will build a pipeline of future top researchers through excellent educational activities. In this way, the Center will incubate and form a new generation of multidisciplinary skin immunology researchers, ready to reshape the field for decades to come.

From the start, we will collaborate across specialties, institutions and geographies. The Skin Immunology Center will aim to have a total of 60 members in the core member research groups when fully operational, a critical mass allowing it to contribute significantly to raising the level and quality of research and education in inflammatory skin diseases.

The existing LEO Foundation Center for Cutaneous Drug Delivery will become an associated and collaborating partner. The Skin Immunology Center will integrate and advance basic and clinical science approaches to skin disease and develop future leaders in the field, while increasing knowledge and awareness of skin and skin diseases among medical professionals, patients and the public.

Grantee: Matthias Mann and Beatrice Dyring-Andersen, University of Copenhagen, Denmark

Grant: 100,000 DKK

The skin is an amazing and complex organ that comprises multiple layers and cell types that are functionally distinct.

The aim of this study is to characterize the molecular composition of the healthy human skin by creating an atlas of all the proteins expressed in healthy skin as a function of their spatial location as well as its major cell types.

This atlas, comprising the identification of a global proteomic composition of human skin, will provide an important resource to the community studying the physiology and cell biology of the skin and serve as a basis for future studies comparing the proteomes of inflammatory and oncologic skin diseases.

Publication of the skin atlas will be accompanied by a freely accessible and well-advertised web page portal where information on proteins of interest and their protein profiles in the layers of the skin will be easily available.

Grantee: Valentina Greco, Yale University, New Haven, Connecticut, USA

Grant: 146,536 DKK

The 2019 Gordon Research Conference on Epithelial Differentiation and Keratinization (GRC-EDK) is the premier international meeting in epithelial biology since 1979. It showcases the latest conceptual and technological advances in epithelial biology bridging basic and translational research.

This 2019 meeting entitled “Innovations in basic and translational epithelial biology” aims to bring together preeminent speakers at the forefront of epithelia development, stem cell biology, cell biology, pathology and therapy.

The main objective is to discuss latest developments and generate synergistic approaches towards future discoveries and therapeutic prospects. To ensure this, over 30% of speakers are from outside the immediate field, 50% did not speak in the 2017 meeting, and over 30% will be selected from submitted abstracts. Finally, a power hour will open a debate on ways to recognize and tackle discriminations in science.

Trainee mentorship will be promoted through the 4th Gordon Research Seminar on Epithelial Differentiation and Keratinization (GRS-EDK), immediately preceding the GRC-EDK. GRS meetings are organized and featured by trainee scientists providing a unique opportunity to discuss their research and develop life-long collaborations.

The GRS-EDK will also feature a career mentoring panel discussion with emphases on transitioning to independence, careers in academia versus industry, and the importance of gender and racial diversity within science. Collectively, this GRC/GRS will move forward cutting-edge research in the area of skin biology, promote translation of key research findings to clinical practice, and further the careers of early stage investigators to maintain the highest level of innovation of this field in the future.

Grantee: Patrick Zeeuwen, Radboud University Medical Center, Nijmegen, The Netherlands

Grant: 2,545,944 DKK

Psoriasis is highly prevalent and has a significant medical and socio-economic impact.

The prevailing dogma has been that abnormalities of the adaptive immune system were primary, but genetic studies have highlighted the importance of local skin-specific factors. We and others have identified epidermis-specific innate immunity genes, like beta-defensins and Late Cornified Envelope (LCE) genes, to be associated with disease development.

We recently made two exciting observations. First, deletion of LCE3B and LCE3C does not merely imply the loss of two genes but has a genomic effect that leads to a strong induction of the flanking LCE3A gene. Secondly, we found that LCE proteins, and LCE3A in particular, have broad-spectrum antimicrobial activity. We hypothesize that the LCE3B/C-del status affects the cutaneous host defense repertoire thereby shaping the skin microbiome. We aim to investigate the biology of LCE genes and to translate these findings to our understanding of psoriasis pathogenesis.

Key objectives are to:

  1. assess the antimicrobial activity and specificity of all LCEs and their synergy with other antimicrobial proteins. This will be investigated by metagenomic approaches and classical in vitro microbiological assays, using recombinant and synthetic LCE proteins and peptides derived thereof
  2. investigate LCE3B/C-del in isogenic 3D-skin equivalents in vitro generated from the immortalized human keratinocyte N/TERT cell line. Deletions of other LCE genes or their regulatory sequences will be made using CRISPR/Cas9 technology. Effects on epidermal biology relevant to psoriasis will be studied and include antimicrobial host defense, innate immune response and skin barrier function

Grantee: George Cotsarelis, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA

Grant: 3,793,808 DKK

Androgenetic alopecia (AGA, Male or Female Pattern Baldness) is the most common type of hair loss, affecting approximately 50% of men and 30% of women by the age of 50.

Current therapies, including pharmaceutical and surgical interventions, are either marginally effective or expensive with significant limitations. Over the last decade, breakthroughs made in the field of adult stem cells have laid the foundation for a cell-based approach to tissue and organ regeneration. Cell-based therapies will comprise a new wave of medical breakthroughs.

In this study we propose to produce human hair follicles from induced pluripotent stem (iPS) cells by directing these cells to form the two types of cells that are needed for human hair formation, namely the human hair follicle epidermal cells and the hair inductive dermal fibroblasts.

We will combine our hair biology and tissue-engineering expertise to generate early stage human hair follicles in culture that can be implanted into an animal model to grow into a mature hair. The long-term goals are to develop an innovative cell-based treatment for hair loss and an in vitro platform for testing hair growth compounds.

Beneficiary: Alex Rojas Bie Thomsen, Columbia University Medical Center

Grant: 3.600.308 DKK

Melanoma is the deadliest form of skin cancer with few treatment options to patients with advanced metastatic disease.

Melanoma metastasis to lymph nodes is associated with expression of the chemokine receptor CCR7, a member of the G protein-coupled receptors (GPCRs) superfamily that promote cell migration of immune cells. Classically, upon agonist stimulation, GPCRs at the cell membrane activate heterotrimeric G proteins, causing downstream signaling throughout the cell. In order to terminate G protein signaling, cells have devised a specialized desensitization mechanism that includes receptor phosphorylation by GPCR kinases and subsequent recruitment of β-arrestins (βarrs) to the phosphorylated receptors. The GPCR–βarrs interaction both blocks the G proteinbinding site and promotes receptor endocytosis.

However, we recently discovered that some GPCRs interact with G proteins and βarrs simultaneously to form GPCR–G protein–βarr ‘megaplexes’, which allows the receptor to continue to stimulate G protein signaling while being internalized into endosomes by βarrs. Our preliminary results suggest that CCR7 forms megaplexes and promotes G protein signaling from internalized compartments. Interestingly, endosomal signaling, in general, is highly involved in cell migration, and different proteins are trafficked between plasma membrane and endosomes during this process. Thus, the proposed project aims to investigate the involvement of endosomal CCR7 signaling in melanoma cell migration. Furthermore, using a combination of highly advanced cryo-electron tomography and APEX2 proteomics, we will visualize the mechanism of CCR7-mediated melanoma cell migration protein-by-protein. Such detailed mechanistic knowledge will assist in designing innovative therapeutics to treat metastatic malignant melanoma.

 

Beneficiary: Jan J. Enghild, Aarhus University

Grant: 3.045.231 DKK

Severe eczema, also known as atopic dermatitis (AD) is the most common inflammatory skin disease resulting in itchy, inflamed, and swollen skin that is very susceptible to infection. It is estimated that 15-20% of all children and 2-10% of adults are affected, without effective treatment.

Because of this, significant public health burden and the lack of safe and effective treatments, there is a need for novel targeted therapeutics that can help manage symptoms and improve the quality of life for the patients.

The protein periostin is expressed in the skin and is implicated in AD. Significantly, studies have shown that the elimination of periostin in an AD mouse model reduces or completely removes the symptoms making periostin an apparent therapeutic target. However, the physiological functions of periostin remains unclear and a reduction or elimination of the protein in the skin could have severe side effects.

Therefore, a deeper understanding of the physiological role in healthy and diseased skin must be established. The interdisciplinary research team behind this project propose to address these issues and establish the function of periostin using in vitro and in vivo experimental setups including primary cell cultures, zebrafish, mouse models and human specimens combined with advanced biochemical methods. Novel therapeutics are urgently needed, and this project aim is to establish a strategy for the development of new treatment paradigms for AD, leading towards novel, innovative therapeutic strategies.

Beneficiary: Samir Mitragotri, Harvard John A. Paulson School of Engineering and Applied Sciences

Grant: 2.000.043 DKK

We will develop a novel ionic-liquid formulation for topical delivery of nucleic acids into the skin.

Our ionic liquid enhances lipophilicity of nucleic acids by ~100,000,000 fold and enhances their penetration into the skin. We will demonstrate the feasibility of the platform through delivery and efficacy of two siRNAs. The resulting platform is expected to have broad applications to other nucleic acid drugs including mRNA for the treatment of a wide range of dermatological conditions.

Our ionic liquid platform will open new opportunities for the treatment of dermatological conditions.

Beneficiary: David M. Sabatini, Whitehead Institute of Biomedical Research

Grant: 1.278.270 DKK

Studies in human populations have identified dozens of pigmentation genes, many of which encode proteins with well-understood functions, such as in melanocyte development, melanin biosynthesis, and the biogenesis and trafficking of specialized melanin-containing organelles called melanosomes.

Yet, there are other pigmentation genes that we know much less about, such as those that encode putative transporter proteins on the melanosome surface. These putative melanosomal transporters have been reported to import precursor metabolites for melanin synthesis or regulate melanosomal pH; however, many of these findings have been controversial or speculative. Deciphering the molecular function of these putative transporters and their physiological substrates is crucial to our understanding of pigmentation.

To address this problem, we propose to determine the metabolite composition of melanosomes and define the role of individual transporters in melanosomal function. We will develop a purification method to rapidly isolate intact melanosomes and analyse them by liquid chromatography and mass spectrometry to compile the first catalog of melanosomal metabolites. We will subsequently characterize SLC45A2, a putative melanosomal transporter that modulates human pigmentation in response to sunlight. By comparing the metabolite profile of wild-type versus SLC45A2-deficient melanosomes, we will identify candidate SLC45A2 substrates and validate them using biochemical assays, a workflow that will be applied to other putative melanosomal transporters.

This study will present the first detailed analysis of melanosome metabolites, as well as identify key metabolites and their transporters essential for melanogenesis. This work could inform new ways to modulate pigmentation and treat pigmentation pathologies.

Beneficiary: Merete Hædersdal, Bispebjerg Hospital

Grant: 2.358.825 DKK

Squamous cell carcinoma (SCC) together with basal cell carcinoma comprises the absolute majority of non-melanoma skin cancers, affecting 150,000 persons in Denmark, equivalent to 3% of the population.

SCC’s cost is consequently substantial, reflected by notable patient morbidity, heavy socioeconomic burdens and significant mortality in immunosuppressed populations.

In oncology, systemic immunotherapies with PD1 and CTLA4 antibodies have had revolutionizing impact on clinical cancer treatment. Recognizing the immense potential of these strategies also for SCC, our vision is to pioneer a new local treatment approach by harnessing the immune system to combat SCC, while at the same time avoiding side effects associated with systemic treatment.

In a three-tiered translational project, we thus aim to deliver PD1 and CTLA4 antibodies through the skin using ablative fractional laser (AFL), effectively opening the door to implementation of topical SCC immunotherapy. The project is executed in collaboration with the Wellman Center at Harvard Medical School and Center for Cancer Immune Therapy at Herlev Hospital. The 3-year research plan comprises preclinical studies on biodistribution and pharmacokinetics in healthy skin, a proof-of-concept study in a well-established murine model for human SCC, and an explorative clinical study in SCC patients from the skin cancer clinic at Bispebjerg Hospital. For patients, topical immunotherapy may constitute a safe treatment with decreased morbidity and the prospect of potentially reduced risk of future SCC occurrence. This in turn will lower the socioeconomic burden of repeated treatments for a large cancer patient group, including high-risk immunosuppressed patients such as organ transplant recipients.

Beneficiary: Kai Kisand, University of Tartu, Institute of Biomedicine and Translational Medicine; University of Tartu; Ravila Str. 19; Tartu 50411; Estonia

Grant: DKK 4.908.566

Melanoma is a very aggressive type of cancer that affects people at their most productive period of the life. As most of the diagnosed patients should have a long life still ahead a cure of the disease is highly desired.

Cancer immunotherapy with checkpoint inhibitors and T cell adoptive therapy have established the crucial role of T cell responses in melanoma as well as in many other cancers. Successful immunotherapy of melanoma is often associated with vitiligo as a side effect indicating the importance of targeting the antigenic epitopes that are shared between melanocytes and melanoma cells.

However, melanocyte antigens are “self” and T cell receptor (TCR) specificities that recognise such epitopes with high affinity are deleted during their maturation in the thymus. To find high-affinity TCRs specific for melanocyte/melanoma antigens we will interrogate the TCR repertoire of a patient population that is defective in their central (thymic) tolerance induction mechanisms due to mutations in autoimmune regulator gene, and who develop vitiligo as one of their disease manifestations.

We expect to identify several TCR specificities that recognise melanocyte/melanoma antigenic epitopes. This information can be used for designing genetically modified T cells for adoptive treatment of melanoma patients, and to advance the knowledge about vitiligo pathogenesis and mechanisms of central tolerance induction.

Beneficiary: Kathryn Browning, LEO Foundation Centre for Cutaneous Drug Delivery (LFCCDD), Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark

Grant: DKK 2.234.415

Atopic dermatitis (AD) is a chronic disorder caused by the improper function of the skins barrier layer, the stratum corneum (SC). It is thought to affect between 15 and 30% of children and up to 10% of adults.

The need to develop drugs and drug delivery vehicles which effectively, and possibly specifically, interact with the compromised skin of AD patients is of great importance.

However, to date most pre-clinical trials utilise healthy skin, excised from surgical procedures, to investigate the penetration and interactions of drugs targeted to skin disease. This approach does not accurately represent lesional or diseased stratum corneum.

This project aims to develop models of the stratum corneum to compare the lipid multilayer structure and interactions of healthy and atopic dermatitis (AD) lesional stratum corneum. Key to the success of these models is access to a wide variety of skin lipids not commercially available and crucial to the realistic self-assembly of the lipid multilayers observed in SC.

An example of a currently unavailable lipid is the long chain esterified ceramides, Ceramide[EOS], which has been linked to the formation of long periodicity phases and lower permeability in SC and is often deficient in AD patients.2-4 These lipids will be obtained by extraction, separation and purification of ceramides from pig skin SC. Lipid mixtures of ratios found in healthy and AD lesional skin will then be self-assembled on a solid support and investigated for interactions with drugs and drug delivery vehicles using neutron reflection, which offers unique opportunities for angstrom level structural resolution and, through selective deuteration, the ability to highlight specific components of the system to improve contrast.

Beneficiary: Mariena van der Plas, University of Copenhagen, Faculty of Health and Medical Sciences, Department of Pharmacy, Universitetsparken 2, Copenhagen 2100, Denmark

Grant: DKK 2.745.375

Proper wound healing is a fundamental survival mechanism and dysfunctions cause significant disease, such as seen in infections after burns, trauma and surgery, as well as in non-healing ulcers.

Currently, the prevalence of non-healing wounds is estimated to be over 40 million worldwide, a number projected to rise with 6-9% annually, due to aging of the population and the increasing incidence of diseases that contribute to nonhealing ulcer development, such as obesity and diabetes.

There is a great and unmet need for novel treatments for improved healing, and thus better predictors for wound healing outcomes are essential. Given the importance of innate immunity and microbial interactions for development of impaired wound healing, the aim of this project is to define novel prognostic and diagnostic biomarkers for assessment of wound healing and infection risk.

For this purpose, we will use state-of-the-art techniques for peptidomics mass spectrometry. This unique approach, without the classical trypsin digestion of the samples, will give actual insight in processes occurring in the wound bed, e.g. enzymatic activity, infection, inflammation, and angiogenesis, instead of just reporting the presence of a protein, independent of the state it is in.

Furthermore, we will set up biological models for validation of biomarkers, as well as novel treatments. Together, the outcomes of these studies have the potential to improve diagnostic evaluations of wounds, and will enable us to develop novel treatment concepts for early prevention of infection, leading to improved healing results for large and significant patient groups.

Beneficiary: Dr. Rudolf Jaenisch, Member, Whitehead Institute and Professor, Department of Biology, Massachusetts Institute of Technology, MA, USA

Grant: DKK 2.476.836

Two major challenges when using mouse models to model human cancers such as melanoma are that the human tumor cells transplanted to mice 1) represent the end-stage of the disease and 2) that the host animals are usually immunocompromised.

Thus, these models fail to actually show development of the disease and they fail to display the ongoing interaction between melanoma cells and the immune system as the disease progresses.

To curb these two shortcomings, the team led by Rudolf Jaenisch of Massachusetts Institute of Technology, has set out to create an experimental model system that will make it possible to study initiation, progression, and manifestation of human melanoma in immune competent host animals.

Their basis is generation of human-mouse neural crest chimeras – where mice embryos are introduced with human neural crest cells carrying the genetic dispositions alleged to lead to development of the particular cancer – and their goal is a model that has the potential to show how melanoma cells evade the immune system.

Given a positive outcome, this innovative project can help devise strategies to improve the effectiveness of current immunotherapies, to test novel immunotherapies, and to identify novel targets in melanoma treatment.

 

Project group

Malkiel Cohen, Postdoctoral researcher

Kristin Andrykovich, Graduate Assistant

Beneficiary: Prof. Dr. Andrew G. Myers, Amory Houghton Professor of Chemistry Harvard University, Cambridge, MA, USA

Grant: DKK 3.108.110

Many common skin infections are caused by the Gram-positive bacterial species Staphylococcus aureus and Streptococcus pyogenes. The infections lead to conditions ranging in severity from minor folliculitis to life threatening skin reactions. If not managed successfully, they may escalate into lethal systemic infections.

Commonly, these diseases are treated with clindamycin, a prototypical member of the wide-ranging so-called lincosamide antibiotic class. Its clinical importance is underlined by the World Health Organization’s listing of it as an essential medicine. In the past decades, however, prevalence of in particular lincosamide resistant Staphylococci and Streptococci has risen sharply. The rise threatens to diminish clindamycin’s usability in the future, even render it obsolete.

In the course of this project, the team led by Andrew G. Myers of Havard University, will seek to address this growing unmet medical need by synthetic discovery efforts focused on the lincosamide class.

The team’s preliminary results indicate that new lincosamides uncovered in this fashion are able to address the contemporary resistance threats: Many of the compounds designed, synthesised, and evaluated by the team to date have shown themselves active against multidrug-resistant clinical isolates of Staphylococci and Streptococci, and at the same time they demonstrate favourable pharmacokinetic and safety profiles.

The team expects that it can uncover new candidates displaying expanded spectra of action against MDR and Gram-negative bacteria. The expected results can then be used to advance refined lead candidates capable of demonstrating efficacy in in vivo murine models of skin infection, and thus yield substantial promise for further clinical development of actual treatments.

 

Project group

Dr. Amarnath Pisipati, Postdoctoral microbiologist

Matthew J. Mitcheltree, PhD student, chemistry

Ioana Moga, PhD student, chemistry

Katherine J. Silvestre, PhD student, chemistry

 

International affiliation

The Institut Pasteur, Annecy, France – International Course on Antibiotics and Resistance (ICARe), Organizing Committee, Core Faculty

Beneficiaries: Professor Gregor B. Jemec, Department of Dermatology, Zealand University Hospital, Roskilde, Denmark, and Assoc. Professor Ole B. V. Pedersen, Department of Clinical Immunology, Næstved Hospital, Denmark

Grant: DKK 5.770.000

In this study, the group led by Professor Gregor Jemec of Roskilde Hospital has set out to identify new genes for the development of a long line of common dermatological conditions, including deep skin infections, warts, fungal infections, and eczema.

Many of these common skin diseases are still poorly understood and the treatments often insufficient. A study of the genetics of these disorders will help increase the understanding of the pathogenic mechanisms. The study will have its origin in Denmark and be based on unique national biobanks, national registries, and with extensive genetic analyses done in collaboration with deCODE Genetics, Iceland.

This is possible due to the growing number of Danish large-scale biobanks as well as biobank based scientific studies suited for further genetic studies. The largest genetic study in Denmark is the Danish Blood Donor Study (DBDS) in which the genome wide association (GWA) arrays have been analysed on 110,000 research participants.

In addition to this cohort, Jemec’s group is currently pursuing genetic testing on the Copenhagen Hospital Biobank (CHB) that includes samples from around 350,000 patients. Both of these biobanks have established a collaboration with deCODE Genetics, Iceland – one of the leading genetic research centers in the world.

 

Project Group

Henrik Ullum, Professor, Department of Clinical Immunology, Rigshospitalet

Søren Brunak, Professor, Center for Protein Research (CPR), Copenhagen University

Simon Francis Thomsen, Professor, Department of Dermatology, Bispebjerg Hospital

Claus Zachariae, Professor, Department of Dermatology, Gentofte Hospital

 

International affiliations

Ingileif Jonsdottir, Professor, deCODE Genetics, Iceland

Errol Prens, Professor, Department of Dermatology, Erasmus University, Rotterdam, Netherlands

Christos Zouboulis, Professor, Department of Dermatology, Brandenburg Medical School Theodor Fontane, Dessau, Germany

Beneficiaries: Dr Simon G. Danby, Independent Research Fellow, The University of Sheffield Medical School, United Kingdom

Grant: DKK 390.506

With this grant, the group led by Simon G. Danby seeks a potentially important technological addition to the ongoing A longitudinal investigation of skin barrier development from birth and the validation of early predictors of Atopic dermatitis (AD) risk: the skin testing for atopic dermatitis risk (STAR) trial (see Grants 2017).

This addition may prove valuable to the group’s envisioned paradigm shift – from management of established AD to primary prevention of the condition.

More specifically, the group will include enhanced ATR-FTIR spectroscopy to quantify biomarkers of skin barrier condition and AD severity in newborns. While existing spectroscopy works in adults and children, its sensitivity has been proven unsatisfactory when measuring newborns.

Working with the equipment manufacturer, the group has developed a solution that increases sensitivity 6-fold. This increase can help better prediction of the risk of AD in the newborn and thus enable targeted emollient intervention right from birth – potentially leading to a reduction of the incidence of the condition as increasing evidence suggests that topical emollient therapy can prevent the initial onset of AD by 50%.

AD is a very common chronic inflammatory skin condition affecting around 20% of children worldwide. The disease often heralds development of allergic diseases such as food allergy, asthma, and allergic rhinitis.

Project Group

Prof. Michael J. Cork and Mr J. Chittock, The University of Sheffield, United Kingdom

Dame Prof. Tina Lavender and Dr Alison Cooke, The University of Manchester, United Kingdom