Grant geography: Germany

Grant category: Research Grants in open competition

Year: 2023

Geography: Germany

Friedrich Götz’s project aims to elucidate the role of bacteria-derived neurotransmitters in the development and progression of diabetic foot ulcers (DFU) and DFU-associated peripheral neuropathy (DPN).

A diabetic foot ulcer (DFU) is a poorly healing open wound that occurs in about 15% of patients with diabetes. Of those who develop DFU, 6% will be hospitalized due to infection or other ulcer-related complications. Previously, Friedrich Götz and his team have found evidence that neurotransmitter-producing bacteria of the skin (here termed neuromicrobiota) may have an impact on the healing process. However, it remains unknown whether the effects are beneficial or detrimental to wound healing.

In Friedrich Götz’s project it is hypothesized that permanent stimulation of neuronal skin receptors is more detrimental for wound healing. Through a close collaboration with the Trauma Surgery at the University Tübingen, BG Clinic Tübingen which treats ~200 DFU patients/year, samples will be analyzed for a variety of parameters, including neurotransmitter content, microbiome and metagenome composition, and impact of neurochemicals on wound healing. These will be compared to samples from healthy subjects taken at similar sites.

The goal of the project is to elucidate the role of bacteria-derived neurotransmitters in the development and progression of DFU and DFU-associated peripheral neuropathy (DPN). Friedrich Götz’s project will substantially aid the scientific understanding of DFUs and may provide potential for clinical application. If bacterial-derived neurotransmitters are found to have an impact on wound healing and progression of DFU, then this may open a new avenue for therapeutic approaches to treat DFU.

Grant category: Research Grants in open competition

Year: 2022

Geography: Germany

The aim of Catherin Niemann’s project is to understand the biologic events during sebaceous gland differentiation, tissue remodeling, and regeneration.

Sebaceous glands (SGs) are critical for the physiological balance and barrier function of mammalian skin. SG dysfunction is associated with a variety of skin diseases, including acne. Despite recent advances using mutant mouse models with SG defects, the main drivers of normal SG functions remain incompletely understood. Therefore, a better understanding of how SG physiology and sebum production (an oily mixture produced by sebocytes, cells of the sebaceous gland) are regulated, is a clinical necessity.

Using both in vivo and in vitro models, Catherin’s project will focus on the regulation of SG stem cells, which are the primary responders to stimuli at the interface with the tissue environment. In vivo, Catherin and her team will use a combination of genetic mouse models and high throughput technologies to identify key players controlling normal SG activity. In vitro, the team has developed a 3D cell culture model that will be modelled to mimic SG differentiation to uncover and validate the central mechanisms of SG regulation. This SG-organoid model will be especially beneficial to decipher the specific role of extra-cellular matrix components in SG physiology and to examine the interaction with other cell types, including immune cells, for their impact on SG cell differentiation and contribution to SG defects in disease settings.

The long-term goal of the project is to establish a platform for testing new therapeutic strategies for the treatment of SG disorders.

Grant category: Research Grants in open competition

Year: 2022

Geography: Germany

Michael Bader’s project aims to develop novel angiotensin-converting enzyme 2 (ACE2) inhibitors to be applied to the skin for treating inflammatory skin diseases.

Alpha-melanocyte-stimulating hormone (α-MSH) acting through its receptor, melanocortin 1 receptor (MC1R), is the most important regulator of melanogenesis (i.e., the production of melanin, the pigment of the skin) and also exerts significant anti-inflammatory actions in the skin. Therefore, MC1R may be a significant treatment target for inflammatory skin diseases and for prevention of melanoma, and several agonists are already clinically approved or currently being developed.

Michael and his group have discovered that ACE2 limits melanogenesis in mouse and human skin by degrading α-MSH. Thus, ACE2 inhibition in the skin may be a novel strategy for dermatological diseases by stabilizing α-MSH and thereby activating MC1R.

However, ACE2 is also a protective enzyme in the circulation limiting the actions of the blood pressure regulatory system, the renin-angiotensin system. Therefore, systemic inhibition of ACE2 may cause severe side-effects, making topical application of ACE2-inhibitors preferable.

Michael and his team have already tested a number of available ACE2-inhibiting compounds, but none were suitable for topical application “as-is”. In this project, they will chemically design variants of known ACE2 inhibitors to optimize for skin permeation and test them in a mouse model of vitiligo. If they are successful, these compounds can also be tested in other inflammatory skin diseases, such as acne and psoriasis, for melanoma prevention, and perhaps even for cosmetic applications, such as skin tanning and prevention of hair greying.

Grant category: Research Grants in open competition

Year: 2022

Geography: Germany

Sarah Hedtrich, who is also Associate Professor at the Faculty of Pharmaceutical Sciences of the University of British Columbia, leads this project focusing on developing novel ways to treat genetic skin diseases through intra-skin delivery methods.

Skin diseases caused by specific genetic defects (genodermatoses) are often rare but can be severe and even life threatening – like epidermolysis bullosa. To cure such diseases, the genetic errors which cause the diseases would need to be corrected. In recent years there have been major advances in targeted gene editing – not least with the CRISPR/Cas system which allows for both tissue- and cell-specific correction.

However, while the skin is readily accessible it has two features which impede such treatment: Firstly, the skin’s barrier function makes efficient delivery difficult, and secondly, as the skin is an epithelium with rapid turnover of the cells, a persistent cure involving gene editing must reach the stem cells which lie at the base of the epidermis, the outer layer of the skin.

Sarah and her team, with expertise in both dermatology, gene editing and topical drug delivery, aim to develop such a delivery system for gene correction treatments using microneedles and nanocapsules, and will investigate its efficiency in both human skin samples and bioengineered skin (disease) models.

Grant category: Research Grants in open competition

Year: 2021

Geography: Germany

The project aims to investigate the role of the skin fascia (a membrane structure in the skin) and its interplay with a specific type of “scar-inducing” cells to better understand – and subsequently prevent – formation of scars. These scar-inducing cells express a unique gene marker, but the cell biology and biochemistry driving the scar process are still unknown despite wounds being an extensively studied clinical challenge.  

Yuval Rinkevich and his team will use novel whole skin-fascia explants (scar-in-a-dish) along with fluorescent “scar-forming” cells that can be tracked during contracture scar formation using live imaging to understand the dynamics of the scar process. Along with single-cell RNA sequencing this will help reveal the cellular and molecular basis of the process and make way for a knowledge basis for its improvement in human skin.  

In addition, the project will investigate the potential of several FDA approved small molecules for treatment of contracture scars. 

The research has the potential to change our scientific and medical views of wound repair and open new therapeutic avenues to treat a variety of fibrotic skin conditions. 

Grant category: Research Grants in open competition

Year: 2016

Geography: Denmark, Germany, Netherlands

The study is foreseen to increase the understanding of the skin barrier and immune system in atopic dermatitis.

Through international collaboration with scientists who perform state of the art and pioneering analyses on skin samples as well as national collaboration with immunologists and radiologists, the team will seek to evaluate non-invasive and easily collectable biomarkers that can predict the risk for atopic dermatitis.

The study has the potential to provide insight in atopic dermatitis pathogenesis and the value of promising pre-atopic dermatitis biomarkers that indicate both inflammation and skin barrier barriers dysfunction. This could be used to develop an algorithm that can better predict the onset of atopic dermatitis.

The team’s work may thus substantially increase the understanding of skin biology in neonates, both normal and diseased. The study will also provide a basis for not only future large-scale observational studies, but also randomised controlled studies evaluating the efficacy of preventive skin barrier restoration or anti-inflammatory treatment in selected groups, potentially reducing the incidence and complications of the most common skin disease in childhood.

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.

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.

Link to the meeting homepage.

Grant category: LEO Foundation Awards

Year: 2015

Geography: Germany

Presented to Dr. Kilian Eyerich, Assistant Professor, Experimental Dermato-Immunology, School of Medicine, Technische Universität München, Germany.

Early in his career, Dr. Eyerich studied the cross-talk between keratinocytes and T cells usingco-cultures.His work on the role of Th17 and Th22 cells in the skin has significantly enhanced molecular understanding of atopic dermatitis and psoriasis. Dr. Eyerich has identified a unique group of patients with co-existing inflammatory skin diseases and demonstrated the mutual antagonism of T cells causing atopic dermatitis and psoriasis.

Grant category: LEO Foundation Awards

Year: 2014

Geography: Germany

Presented to Dr. med. Christina Zielinski, research group leader and dermatological fellow, Department of Dermatology and Allergology and Berlin-Brandenburg Center for Regenerative Therapies, Charité University Medicine, Berlin.

Dr. Zielinski’s research focuses on how the body’s immune system protects itself from microbial assault by distinguishing between the body’s own cells and foreign organisms. It examines what happens when the body does not regulate itself in this way and how this affects the development of autoimmune diseases such as psoriasis and multiple sclerosis. Insights gained from these studies are expected to identify molecular cues that can be exploited in order to develop immune modulation therapies.