The Young Investigator Program (YIP) of SKINTEGRITY.CH aims at fostering the academic as well as the personal development of doctoral students and postdocs from groups within SKINTEGRITY.CH. The program is steered by the Young Investigators themselves who organize lectures, workshops, social events and more. It thereby serves as a platform to enhance the interaction between the Young Investigators and opens the possibility for Young Investigators to meet people from academia and industry in a casual setting. Young Investigators are nominated by the SKINTEGRITY.CH PIs.
Giuseppe develops functionalized collagen peptides and explores their value as biological probes and biomaterials. He also determines the suitability of targeting peptides for treatment or diagnosis of fibrotic diseases.
KEYWORDS: drug delivery, extracellular vesicles, liposomes, wound healing
Johannes' research focuses on the loading of nucleic acid drugs into stem cell-derived extracellular vesicles (EVs). The aim of the project is to find a suitable method, which would allow the entrapment of different RNA species inside EVs while preserving their unique wound healing properties. Such engineered nanocarriers could potentially ameliorate impaired wound healing processes.
KEYWORDS: lymphatic vessels, human skin, human fat, sequencing
Aline studies lymphatic vessels in human skin and the underlying adipose tissue. Performing confocal microscopy, single-cell sequencing and in vitro cell culture experiments, she investigates the contribution of lymph flow to shaping the phenotype of the vessel-lining lymphatic endothelial cells in these two different tissue compartments.
Nicole investigates skin-homing pathogenic TH2 cells that participate in inflammatory and malignant skin diseases. These cells are characterised by high expression of both interleukin 9 (IL-9) and its receptor, IL-9R. The focus of my research is to elucidate the function of autocrine and paracrine IL-9 in skin inflammation and to evaluate the potential of its therapeutic manipulation.
KEYWORDS: collagen, drug delivery, lysyl oxyidase, synthetic peptides
Fibrotic diseases represent a major burden on global health. Linus develops molecules for the delivery of therapeutics to treat fibrotic conditions or assist wound healing, exploiting the activity of enzymes that are upregulated during tissue remodelling.
Blaž focuses on metabolic dysregulation in skin fibrosis, with a special interest in systemic sclerosis (SSc). He investigates the role of alpha-ketoglutarate as a new potential treatment strategy to halt myofibroblast activation and suppress fibrotic process in different ex-vivo and in-vivo settings.
KEYWORDS: keratinocytes, proteomics, systems biology, proteolysis
Vahap is studying the role of dermokine in keratinocyte differentiation using CRISPR/Cas9 technology and in vitro skin models. Coupled with advanced mass spectrometry methods, the findings can provide useful insights to extend our comprehension of the mechanisms involved in the epidermal differentiation process.
An important aspect of Michael's research is the analysis of the parallels between tissue repair and cancer at the molecular and cellular level, with a focus on the role of growth factors and matrisomes. In addition, he is currently developing new therapeutic strategies targeting the epithelial stromal crosstalk for the treatment of skin fibrosis and cancer.
Fibrosis is the final path of nearly every form of chronic disease, including skin fibrotic disease, and it is defined by the excessive accumulation of extracellular matrix produced by fibrogenic fibroblasts. Due to the lack of efficient anti-fibrotic therapies, fibrosis leads to lethal organ failure and mortality. Jing's research project aims to establish vaccination-based immunotherapy that can elicit an antigen-specific cytotoxic T cell response, specifically targeting fibrogenic progenitor cells to ameliorate fibrosis.
KEYWORDS: epithelial stem cells, culture, transplantation, cancer
Stéphanie works in collaboration with her colleagues in dissecting the role of PPAR-β in Squamous Cell Carcinoma (SCC). PPARs are nuclear hormone receptors, which have a role in keratinocyte proliferation, skin wound healing, and in keratinocyte response to inflammation and SCC development.
My current project investigates the potential acceleration of dermal fibroblast proliferation by examining their response to various mechanical stimuli. By combining different stimuli and harnessing the scaffold's mechanotransduction properties, this research explores novel approaches to accelerate tissue regeneration and holds promise for applications in tissue engineering and regenerative medicine.
KEYWORDS: 3D hydrogel scaffold, extracellular matrix, in vitro tumor model, squamous cell carcinoma, tumor spheroids
Investigations into skin cancer and potential therapeutics heavily rely on animal experimentation. Gabriela is working on a 3D scaffold-based alternative to mice xenografts, in which tumor growth and invasion can be measured. The models will be validated by comparing molecular and biophysical signatures of tumors in different microenvironments. This is a collaboration with the Dengjel group at the University of Fribourg.
Michela studies the role of the NLRP1 inflammasome, a protein complex of the innate immunity expressed by human keratinocytes, using a novel 3D model of human skin. This will give insights into the molecular mechanisms underlying skin inflammation and skin cancer development.
KEYWORDS: glia, skin 3D model, squamous cell carcinoma, wound healing
Vilius studies wound healing and squamous cell carcinoma of the skin. He is particularly interested in glia cells (the cells surrounding and supporting peripheral neurons), which have been shown to have a crucial role in both of these processes.
Börte's project focuses on designing an immunomodulatory biomaterial for healing of chronic wounds. By engineering a modular and macroporous scaffold, this work aims to accelerate healing by facilitating in-growth of healthy cells and normalizing aberrant signaling through biomolecule release and inactivation.
New blood vessel ingrowth in skin is critical for the survival of skin grafts and tissue-engineered skin substitutes, because abundant vascularization is an absolute requirement for skin homeostasis, regeneration, and wound healing. Zheng's research is aiming to understand how blood vessels grow in skin tissue and how endothelial cells (the main cell types which form blood vessels) orchestrate with other cell types (e.g. fibroblasts, immune cells, etc.) to ensure normal function of skin.
Danielle's current research focuses on atopic dermatitis, a chronic inflammatory skin disease. She investigates differences between European and African patients concerning the immune response, the barrier function of the skin and associated allergies.
KEYWORDS: hydrogels, materials, biomechanics, skin, 3D models
Lorenza's research focuses on the synthesis of hydrogel materials to develop tuneable 3D culture systems for dermal fibroblasts, allowing to investigate and modulate how different physical and chemical stimuli affect cell responses. The proposal integrates expertise in hydrogel design to mimic the in vivo environment of cells with advanced biomechanics characterization and modelling to provide insight on the physical mechanisms underlying skin function and pathology.
KEYWORDS: androgen-receptor signalling, cancer-associated fibroblasts, fibroblasts activation, melanoma, skin cancer
Dr. Ghosh studies the role of Androgen Receptor (AR) signalling in skin cancer development, with a focus on tumor-stroma interaction and cancer-associated fibroblast activation. Understanding the molecular mechanisms underlying AR signaling in skin cancer can provide insights into potential therapeutic targets and strategies for gender-specific medicine.
Olga studies the interaction of lymphatic vessels and migrating cells in various tumor models such as melanoma and cutaneous T cell lymphoma (CTCL). Using various tumor mouse cell lines, transgenic mouse models and human samples, she studies the influence of the tumor microenvironment on tumor growth, cell activity and motility of migrating cells.
Silicone additive manufacturing has recently become available. Marcel explores how silicone additive manufacturing can be applied to develop soft material bioreactors with integrated functionalities to grow skin models. The aim is to simplify and enhance the robustness of skin model production by developing bioreactors with integrated actuation for extrinsic stimulation or perfusion of the skin models and to get closer to in-vivo conditions.
Eduardo studies the interaction between the skin commensal fungus Malassezia and the host, and the role of the host protein AhR, which senses fungal metabolites, in fungal control, T cell immunity and skin integrity.
KEYWORDS: biomimetic structures, fibroblasts, keratinocytes, material properties, skin regeneration
Tobias studies the influence of the composition and organization of different natural and/or synthetic materials on fibroblasts and keratinocytes with the aim to generate biomimetic skin structures. Gaining insight into the mechanical, structural and biochemical requirements needed for proper cellular activities will not only increase our understanding of the relevance of the microenvironment to physiological pro-cesses, but also close the distance towards the fabrication of clinically relevant skin substitutes for re-generative purposes.
In the context of skin diseases, I study the crosstalk between lymphatics and leucocytes in steady-state and inflammatory conditions. In particular, at a single-cell resolution, I investigate how leucocytes migrate through the lymphatic vessels in the skin, especially dendritic cells. For that, I use 3D-imaging using light sheet microscopy in human skin samples. Thus, this would provide us information to better characterize a therapeutic approach targeting the lymphatics in these pathological contexts.
The peripheral nervous system has been shown to promote carcinogenesis by providing a scaffold for the invasion of cancer cells. More specifically, peripheral glial cells play an active role in cancer progression by facilitating cancer cell dispersion and invasion. However, the mechanisms by which peripheral glial cells promote skin carcinogenesis in vivo is currently poorly understood. Khanh's research addresses this question by using a mouse model of squamous cell carcinoma with inducible depletion of peripheral glial cells. This study aims to contribute to the understanding of squamous cell carcinoma by determining important mechanisms in the development of the disease.
KEYWORDS: age, biomechanics, finite element analysis, mechanical characterization, wounds
Håvar Johan is focusing on the mechanical characterization of skin during the course of different biophysical environments, such as wound healing and intrinsic aging. The objective of his research is to improve our understanding of the biomechanics of the skin and to further develop diagnostic tools for different skin diseases, by utilizing both computational and multiscale experimental techniques.
Jihye studies genetic and epigenetic mechanisms of skin inflammation, with a focus on psoriasis and dermal fibroblasts. The aim is to obtain new insights into potential new targets to treat inflammatory skin diseases.
KEYWORDS: exosomes, wound healing, regenerative medicine, drug delivery
Vadim's research focuses on exosomes' regenerative capabilities and their unique wound healing properties. Exosomes gained recognition as potential candidates to replace stem cells for regenerative medicine applications. They contain more growth factors than stem cells, they are non-immunogenic, targeted by ligands, and cannot become cancerous. The option to load exosomes with cargo broadens the potential therapeutic applications to drug-delivery systems.
KEYWORDS: biomechanics, bioreactors, dermal fibroblasts, mechanobiology, 3D culture
Daniela works experimentally towards unravelling the stretch signature of human skin. Understanding the response of dermal fibroblasts to stretch on a tissue-level as well as on the cell-level will improve our understanding of the physiology, disease pathogenesis and potential mechanotherapies for skin.
KEYWORDS: 3D hydrogels, fibrosis, myofibroblasts, skin
Celine studies how dermal fibroblasts respond to physical changes in their microenvironment, such as dynamic stiffening. The goal is to understand how the mechanical properties of the environment regulates the activation of contractile fibroblasts (myofibroblasts) in 3D. These cells are responsible for wound closure, but also for fibrosis if their activity goes unchecked. Therefore, understanding the contribution of the microenvironment in the regulation of myofibroblast fate will contribute to the development of novel approaches to treat fibrosis-linked diseases.
KEYWORDS: cancer evolution, probabilistic graphical models, single-cell sequencing data analysis
Xiang Ge Luo studies mathematical and computational tools applied to the area of cancer evolution. In particular, she is developing probabilistic models of tumor progression for single-cell sequencing data.
Fabian studies the role and function of T-helper cell subsets, more specifically T-helper cells that secrete the cytokine Interleukin 9. This subset of T-helper cells is termed Th9 cells and is associated with acute antigen-mediated skin inflammation. The focus of his research lies in understanding the biological and metabolic properties of these T-helper cells in order to identify therapeutic targets for skin inflammation.
Anastasiya studies various chemomechanical cues that dermal fibroblasts experience when skin is stretched. Understanding the effects of such mechanically coupled stimuli in the skin will improve our understanding of disease pathogenesis and help us to develop improved mechanotherapies for the skin.
Brenno develops peptide probes that anneal to collagen in fibrotic tissues. The specificity of these probes arises from the combination of collagen mimetic peptides and unnatural amino acids that crosslink to the extracellular matrix. By investigating and improving the binding of these synthetic peptides to natural collagen he aims to expand the available tools for the therapy and diagnosis of fibrotic disease.
KEYWORDS: 3D hydrogels, biomechanics, fibroblasts, mechanobiology, co-culture systems
Jaimie is developing tunable 3D culture systems to investigate how changes to the microenvironment affect dermal fibroblast phenotype. A current aim is a phototunable platform to explore how dynamic changes to mechanical properties, rather than static conditions, affect myofibroblast activation, which is relevant in fibrotic diseases. Future aims will involve incorporating immune cells, such as macrophages, into these systems to investigate compatibility and effects on identified mechanotransduction pathways.
Peripheral glia dedifferentiate from their mature form following skin injury and beneficially promote skin wound healing. Recently, we also showed that glia promote cutaneous squamous cell carcinoma (cSCC) initiation, as upon glia depletion cSCC formation is drastically reduced. However, the underlying mechanisms with which glia promote skin repair and cSCC initiation remain poorly understood. Sofia's research aims to investigate the role of peripheral glia cells in wound healing and cSCC. In particular, her research focuses on the interactions between glia and fibroblasts and glia and immune cells in these processes.
Yasutaka's research question is "What kind of cutaneous cell types work together closely, and how do they intereact with each other in the skin?" He uses spatial transcriptomics assays and collects spatial gene expression information from atopic dermatitis patients and healthy controls. Yasutaka identified detailed cell-cell crosstalk in the skin, which helps to understand the complex pathogenesis of atopic dermatitis.
Fibrotic diseases, including skin fibrotic diseases, are characterized by high morbidity and significantly impaired life quality of the patients. Clinical trials with targeted therapies have shown to slow down disease progression, but not to block it. Currently, there is still a high unmet need for new antifibrotic therapies. The focus of my research is to characterize mechanisms of fibrosis and to identify novel antifibrotic targets.
Jessica studies the influence of various extrinsic factors on in vitro skin model quality. Understanding the effects of such external stresses will help us to develop new additively manufactured bioreactors, skin culturing devices and technically assisted workflows to enhance the robustness of skin model production.
KEYWORDS: lysyl oxidase, collagen, synthetic peptides, small molecules
Laura investigates the selectivity of lysyl oxidases (LOX) using synthetic collagen peptides and small molecule probes. Her research will shed more light on LOX reactivity and improve our fundamental understanding of LOX-mediated collagen cross-linking during tissue development and disease.
KEYWORDS: CD8+ T cells, immunoregulation, microbiota
Julia studies unconventional CD8+ T cells, which recognize bacterial peptides via non-classical MHC class I molecules. She thereby aims to elucidate conserved pathways of commensal and pathogen recognition in barrier tissues like skin or gut, and their influence on immunoregulation and effector functions in health and disease.
Gabriel investigates the mechanical behaviour of human skin. He employs a quadriphasic computational model and develops novel experiments in parallel. His objectives are to quantify the electrical potential induced by skin stretch, the associated anisotropic permeability properties and chemical potential gradients, and its connection with transepidermal water loss. Deeper understanding of skin biomechanics helps us predict and tailor the conditions for mechanobiological studies ex-vivo and in-vivo.
KEYWORDS: 3D cell culture, extracellular matrix, fibroblasts, proteomics, skin cancer
Sibilla works on characterizing and modelling cutaneous squamous cell carcinoma by mass spectrometry-based proteomics and three-dimensional cell culture systems. This approach allows to study molecular mechanisms that promote skin cancer cell proliferation and invasion.
Stefanie investigates the functional role of IL-18 in inflammatory skin disease, specifically atopic dermatitis. The focus of her work lies on elucidating the main source of this proinflammatory cytokine, how its secretion is regulated, and its functional effect on pathogenic TH2 cells. Altogether, her research contributes to the identification of potential therapeutic targets for inflammatory skin disease.
Ramon studies the early development of cutaneous squamous cell carcinoma (a frequent type of skin cancer that originates from transformed keratinocytes) on a single cell level. A better understanding of these mechanisms could lead to improved prevention and treatment of such tumors. Moreover, he is investigating the cellular mechanisms of skin toxicities induced by novel immunotherapies against melanoma.
During vertebrate embryonic development, neural crest stem cells give rise to a plethora of cell types, including peripheral glial cells and endoneurial fibroblasts in peripheral nerves (Joseph et al., 2004; Zurkirchen & Sommer, 2017). In the adult, neural crest-derived cells from peripheral nerves have been shown to promote skin wound healing, although the mechanisms underlying this process are largely unknown. Salome's research addresses how neural-crest derived cells contribute to the wound healing process in the skin.
Maša investigates collagen maturation and remodeling by utilizing synthetic peptides and fluorescent sensors. She is expanding the versatility of these chemical tools for visualization and monitoring of lysyl oxidase (LOX)-mediated collagen cross-linking to study fibrotic and malignant diseases.
Using multi-omics single-cell profiling methods (CITE-seq, ATAC-Gene-seq, single-cell immune repertoire profiling), Dr. Tastanova studies cell type composition, heterogeneity and microenvironments of tumors compared to healthy tissues. In particular, she is interested in treatment-induced changes in cutaneous lymphoma, melanoma, and other skin cancers.
Kongchang develops functional polymers and polymer-based biomaterials in different forms, including hydrogels, tissue glues and fibers, to accommodate cells and other bioactive components for skin tissue engineering, protection and regeneration applications.
Lito is establishing 3D whole-mount stainings in human skin to visualize the (lymphatic) vasculature and leucocytes within the dermis. Performing time-lapse confocal / multiphoton imaging in fresh skin, she will study leucocyte migration into and within lymphatic vessels. Alternatively, the method may be used to investigate the activity of adjuvants to induce dendritic cell migration.
KEYWORDS: adipose tissue, inflammatory skin disease, imaging mass cytometry
Reihane studies the immunological functions of subcutaneous adipose tissue (SAT) in the context of skin-based inflammation. She focuses on characterization of immune players in SAT by using novel methodologies for spatial phenotyping of skin tissue at the single cell level. Therefore, modulation of SAT immune responses is an important approach for development of therapies for cutaneous or systemic immune-related diseases.