Barrier diseases

Project 1: Uncovering novel molecular pathomechanisms in AMD by identification of risk SNP binding proteins

Recent advancements in whole genome sequencing have uncovered many genetic variations, so called single nucleotide polymorphisms that correlate with an increased risk to develop age-related macular degeneration during life. Our unique approach aims to discover the biological mechanisms that are affected by these genomic variations, by enrichment and identification of specific proteins and protein complexes which directly bind to the respective genomic regions. As a result from this project, we expect to uncover novel pathways involved in the risk to develop age-related macular degeneration in order to provide the basis for innovative preventive therapies. Since those novel therapies will be based on genome-specific variants, recipients who are most likely to profit due to their genotype can be predicted and a truly personalized intervention could be enabled. The project “Identification of Protein Complexes Binding to Genomic AMD Risk Variants” is currently funded by the BrightFocus Foundation (Principal investigator Dr. Stefanie Hauck, http://www.brightfocus.org/macular/grant/m2015370)

Project 2: Influence of cigarette smoke exposure on cell layer integrity of retinal pigment epithelial cells

Apart from age, cigarette smoke is the main risk factor for age-related macular degeneration, a neurodegenerative eye disease usually affecting older adults and resulting in a loss of vision in the center of the visual field. Oxidative stress, antioxidant depletion and complement activation due to tobacco smoke are thought to lead to atrophy of retinal pigment epithelial (RPE) cells, resulting in the detachment of the retina and loss of photoreceptors. In order to increase the so far limited understanding of cigarette-smoke induced molecular processes, we treat primary RPE cells with different concentrations of cigarette smoke extract and monitor phenotypic alterations as well as changes in protein abundances by label-free quantitative LC-MS/MS based proteomics. By specific targeting of altered biological processes we aim to restore phenotypes of untreated cells and subsequently propose new potential therapeutic entry points for patients suffering from age-related macular degeneration.

Project 3: Chronic hand eczema vs. hand psoriasis - differential diagnosis facilitated by proteomic markers

Aim of this project is to address the urgent medical need for early and reliable differential diagnosis of the skin diseases chronic hand eczema (CHE) and hand psoriasis. Currently, there is a lack of clear molecular, clinical, and laboratory markers for either disease, although their distinction has major implications for therapeutic decisions and outcome and is therefore of great importance for the daily routine of dermatologists. Therefore, we want to analyze the differential protein expression signature in CHE and hand psoriasis using state-of-the-art mass spectrometry (MS) and compare their differential protein expression patterns, both in skin biopsies from patients and in minimal- or non-invasive material like hand sweat or epidermal tape stripping. With this approach we hope to establish a new diagnostic workflow dermatologists can use in daily clinical practice.

The project is currently funded by “Translationale und Klinische Projekte” at HMGU (Principal investigators Dr. Juliane Merl-Pham and PD Dr. Sonja Molin, Klinik und Poliklinik für Dermatologie und Allergologie der LMU München).

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