Comprehensive knowledge about the abundance and variation of cell types present at different body sites in healthy skin will unveil body-site dependent molecular and cellular mechanisms underlying phenotypic and functional differences, fundamental knowledge for uncovering body-site dependent susceptibility to skin diseases.
Background & Significance
Skin at distinct anatomical body sites and between sexes has different prevalence for developing skin disorders, including skin cancer. For example, prevalence of both melanoma and non-melanoma skin cancer differ in overall frequency, cancer type, and by gender, however the reasons behind are largely unknown. Recent advanced in single-cell RNA-seq technology have made it possible to profile entire mammalian organs, and for mouse skin, my research has generated a detailed molecular atlas depicting 56 distinct cell types and states, and cell-differentiation processes. However, for human skin such detailed information on the variation of cell types together with their molecular profiles, and how those differ between anatomical body locations, is entirely lacking. In this project, ESR12 will utilize my labs expertise in single-cell transcriptomics, computational analysis and in situ RNA-FISH (all established for skin analysis) to reveal cell-type specific molecular and cellular differences of healthy human skin from different body sites.
The goal is to generate in-depth knowledge about cell-type variation in human skin dependent on body location. The ESR will (1) learn the use and if necessary optimize our current skin dissociation protocol for human skin assuring broad coverage of skin cell types, (2) learn computational single-cell analysis (in parallel with point 3), (3) generate single-cell transcriptomes from different healthy donor body sites aiming to profile 3 body sites each of 3 women and 3 men. Please note: the N of donors and body sites will be increased if necessary (iterative approach), which can be done either by the ESR (depending on the capacity) or via additional help from researcher(s) in my group, (4) in-depth comparison of cell types present at different body sites, and variation between sex, (5, optional) comparison of data from healthy skin focused on specific cell types, e.g. fibroblasts or immune cells, with then available single-cell data sets from non-melanoma skin cancers and/or immune-regulated skin disorders.
optimize biophysical assays for detecting interactions between STATs and small molecule inhibitors;
assess mechanisms of action for known STAT inhibitors and identify novel targets within the STAT signaling pathway;
aid in the identification and optimization of novel STAT inhibitors;
explore the utility of STAT inhibitors in inflammation and cancer prevention.
Enrolment in Doctoral degree(s):
- Karolinska Institute