Accelerating to zero transmission of leprosy in Nepal<\/strong><\/p>\n\n\n\nOne project to receive a grant in the latest round is that by Principal Research Fellow Sarah Dunstan, who hails from the University of Melbourne in Australia. With a focus on two Nepali districts with a high incidence of leprosy, Sarah Dunstan will explore the leprosy-causing bacteria (Mycobacterium leprae). <\/p>\n\n\n\n
Leprosy, despite being both treatable and preventable, remains a neglected tropical disease that causes severe stigmatization, disability, and mental health challenges. Achieving a leprosy-free world requires a deeper understanding of the disease’s pathophysiology, transmission, and the development of effective strategies for prevention and cure. That is what Sarah Dunstan aims to contribute to by collaborating with a network of community health workers in Nepal, who will actively search for leprosy cases. <\/p>\n\n\n\n
The insights gained from this research will enhance interventions for diagnosis, treatment, and vaccine strategies and establish a solid framework to achieve the goal of zero transmission of leprosy.<\/p>\n\n\n\n
Combating \u201cflesh-eating disease\u201d<\/strong><\/p>\n\n\n\nProfessor Thomas Sicheritz-Pont\u00e9n from the University of Copenhagen in Denmark receives a grant for his project which will explore Necrotizing Soft Tissue Infections (NSTI), also known as \u201cflesh-eating disease\u201d. <\/p>\n\n\n\n
Flesh-eating disease is rapidly escalating globally, its infections characterized by aggressive skin manifestations. Although prompt surgery and antibiotics serve as a first line of treatment for NSTI, infections often lead to necrosis and therefore amputation, and in worst cases death. <\/p>\n\n\n\n
Flesh-eating disease is primarily caused by Group A Streptococcus (Strep A), and Thomas Sicheritz-Pont\u00e9n aims therefore to decode Strep A\u2019s genetic makeup, carrying out the fundamental work needed to develop a targeted therapy using bacteria-infecting viruses to kill the bacteria rather than antibiotics. His work will build off collaboration across different research hubs to provide vital insights to help combat NTSI. <\/p>\n\n\n\n
Introducing value-based healthcare in psoriasis<\/strong> treatment<\/strong><\/p>\n\n\n\nProfessor Jo Lambert from Ghent University in Belgium is another researcher to receive a grant for her innovative project, which will trial the feasibility of using a value-based healthcare (VBHC) framework for psoriasis management and treatment. <\/p>\n\n\n\n
The novelty of a VBHC framework lies in its optimization of value for patients, as it proposes a model in which providers, including hospitals and physicians, are paid based on patient health outcomes. Jo Lambert will conduct a clinical study in which new patients attending a dedicated psoriasis clinic (PsoPlus) of the Ghent University Hospital will be followed during at least a period of one year. Created value for psoriasis patients will be evaluated and findings distributed to provide a basis for more efficient psoriasis treatment placing patients in the foreground. <\/p>\n\n\n\n
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Read more about all 14 grantees and their projects below.<\/p>\n\n\n\n
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Adelheid Elbe-B\u00fcrger<\/h3>\n Associate Professor, Medical University of Vienna, DKK 3.1m<\/h5>\n <\/div>\n <\/div>\n <\/div>\n \n
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Skin barrier immune defence against the multidrug-resistant fungal pathogen Candida auris<\/strong><\/p>\nAdelheid Elbe-B\u00fcrger\u2019s project investigates the pathogen:host interplay using ex-vivo skin models in relation to infections by Candida auris \u2013 a multidrug resistant fungus.<\/p>\n
Drug-resistant microorganisms represent a serious human health threat worldwide. Candida auris (C. auris) is an emerging, multidrug-resistant human fungal pathogen. Its pronounced skin tropism (i.e., ability to infect) promotes persistent colonization of the skin and facilitates skin-skin transmission within health care facilities, leading to life-threatening infections of high mortality in immunocompromised patients.<\/p>\n
The lack of clinically relevant primary human skin models with a disrupted barrier function has been a serious impediment to better understand the C. auris:host interplay during pathogenesis.<\/p>\n
To counter this, Adelheid Elbe-B\u00fcrger and her team have developed unique, standardized human ex vivo skin models that allow them to study C. auris colonization and penetration as well as identify the immune cells that orchestrate both the recognition and immune defense against this fungus.<\/p>\n
In Adelheid Elbe-B\u00fcrger\u2019s project infected skin biopsies will be analyzed by single-cell RNA-sequencing, flow cytometry as well as confocal microscopy. Culture supernatants will be subjected to multiplex proteomics (i.e., a way to analyze many proteins simultaneously) to decipher host components governing fungal:host interactions.<\/p>\n
The overarching aim is that the results will advance the understanding of tissue-specific mechanisms of anti-C. auris defense and may help to pave the way for improved therapeutic options.<\/p>\n\n <\/div>\n
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Cory Simpson<\/h3>\n Assistant Professor, University of Washington, USA, DKK 4.1m<\/h5>\n <\/div>\n <\/div>\n <\/div>\n \n
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Modeling Hailey-Hailey disease to delineate its pathogenesis and identify therapeutic strategies\u00a0<\/strong><\/p>\nCory Simpson\u2019s project aims to investigate how mutations in the gene encoding the calcium pump SPCA1 cause the skin blistering disease Hailey-Hailey Disease (HHD) using human cellular and tissue models.<\/p>\n
The epidermis forms the body\u2019s outer armor from multiple layers of cells called keratinocytes, which assemble strong connections (desmosomes) to seal the skin tissue and prevent wounds. Several rare blistering disorders are linked to autoantibodies or gene mutations that disrupt desmosomes, causing keratinocyte splitting and skin breakdown. While autoimmune blistering diseases can be controlled by suppressing the immune system, treatments remain elusive for inherited blistering diseases.<\/p>\n
One of these is Hailey-Hailey disease (HHD), which causes recurrent wounds, pain, and infections, leading to stigmatization of patients. Mutations in the ATP2C1 gene, which encodes the calcium pump SPCA1, were linked to HHD more than 20 years ago, yet the disease still lacks any approved therapies.<\/p>\n
While it is known that SPCA1 resides in the Golgi apparatus (an organelle inside the cell responsible for protein processing and trafficking), our limited understanding of how SPCA1 deficiency compromises skin integrity has stalled drug development for HHD; moreover, mice engineered to lack SPCA1 did not replicate HHD.<\/p>\n
Cory Simpson and his team at the University of Washington have built human cellular and tissue models of HHD to define what drives the disease and to discover new treatments. Their preliminary analysis of ATP2C1 mutant keratinocytes revealed impaired expression and trafficking of adhesive proteins, but also identified stress signals from mis-folded proteins and reactive oxygen species.<\/p>\n
In this project, Cory Simpson and team will determine how these cellular dysfunctions compromise keratinocyte cohesion to cause skin blistering and test if cell stress pathways could serve as therapeutic targets for HHD.<\/p>\n\n <\/div>\n
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Friedrich G\u00f6tz<\/h3>\n Professor, University of T\u00fcbingen, Germany, DKK 2.5m<\/h5>\n <\/div>\n <\/div>\n <\/div>\n \n
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NEMFU: Impact of neuromicrobiota in diabetic foot ulcers\u00a0<\/strong><\/p>\nFriedrich G\u00f6tz\u2019s 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).<\/p>\n
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 G\u00f6tz 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.<\/p>\n
In Friedrich G\u00f6tz\u2019s 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 T\u00fcbingen, BG Clinic T\u00fcbingen 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.<\/p>\n
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 G\u00f6tz\u2019s 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.<\/p>\n\n <\/div>\n
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