Resource Core B - Modeling of skin disease for mechanistic analysis and therapeutic discovery

Summary – Resource Core B Many technical, logistical and cost barriers hinder efficient and feasible access to high-end experimental approaches in skin research. Efforts by Core B, “Modeling of skin disease for mechanistic analysis and therapeutic discovery” will systematically overcome these barriers for skin researchers by facilitating access to human skin samples, harnessing our expertise in generating and analyzing sophisticated mouse genetic and human iPSC-derived models of skin disease, and providing a streamlined interface with Core C for genomics and transcriptional analyses. In parallel, the entry barriers to skin biology and diseases research will be lowered by providing Pilot Grants to junior investigators and researchers newly entering the skin biology and diseases field, and the costs of high-end technologies will be defrayed by User Scholarships. Core B will offer users specialized technical, clinical and scientific know-how and services in advanced skin research as well as critical research infrastructure by providing A) clinical and histopathological expertise for easy retrieval of normal and diseased human skin and access to efficient multiplexed skin marker analysis for physiological and skin disease studies; B) scientific expertise and service for physiological studies of fundamental skin functions with advanced genetic mouse models and cell isolation and imaging technologies; and C) scientific expertise and service for human skin disease modeling with patient-derived iPSC technology and with CRISPR-based gene editing and expression manipulation for mechanistic analysis and therapeutic target discovery. These goals will specifically be achieved by 1) providing samples from our vast collection of archived normal and diseased human skin; 2) facilitating access to de-identified fresh human skin samples; 3) advanced multiplexed immunohistochemical imaging of marker proteins; 4) aiding in the generation of state-of-the-art genetic mouse models for skin functional studies; 5) providing training in refined isolation technologies for specific skin cell populations; 5) providing training for advanced live imaging in vitro and in vivo; 6) generating patient iPSCs and differentiating them to skin cells to model human skin disease; and 7) studying candidate skin disease genes by generating isogenic mutant and control iPSC-derived skin cells and through Cas9-based gene expression manipulation.