Grants We Funded

Abstract
Long-term objectives We seek to identify and characterize the human fibroblast stem/progenitor cells (FSC) and the tissue origins of the human scar-forming fibroblasts. This will enhance current understanding of the molecular biology of scarring and enable investigation of the response and contribution of these fibroblasts to number of physiological and pathological changes in the skin, like ageing to cancer. The long-term goal is to identify new targetable surface molecules or signaling pathways that can be manipulated to minimize or prevent scar formation and promote regenerative skin repair following wounding. Aim 1. To define the fibroblast stem cells in unwounded human skin. Rationale There is a lack of cell surface markers for isolating human cutaneous fibroblasts for functional and molecular analysis and to determine the identity of the human FSC. Study design Human skin cells will be screened for their surface marker reactivity to a panel of antibodies to identify which surface markers are expressed on human skin cells. Specific antibodies, or combinations of antibodies, will be assessed for their ability to enrich for cells that express fibroblast genes to identify human cutaneous fibroblasts. Fibroblast identity will be confirmed via gene expression analysis and immunostaining. The ability of the identified fibroblast populations to behave as stem cells in vitro and in vivo will be assessed by demonstrating the capacity for serial self-renewal, and the ability to differentiate into the other unique fibroblast cell types. Single cell RNA sequencing, an unbiased analysis of the whole cell transcriptome, will be used to confirm FSC identity, and to determine signaling receptors that regulate survival and expansion at the single cell level. Aim 2. To define the tissue origins of fibroblasts which give rise to scars in wounded human skin. Rationale The human scar-forming fibroblasts may originate from resident cells (endothelial cells, epidermal cells, or pericytes) or from hematopoietic cells in the blood stream (pericytes or monocytes). Study design To investigate which tissue types give rise to fibroblasts in vitro and in vivo, human skin cells will be isolated and stained for pan-surface markers of each of these tissue lineages, isolated using flow cytometry, and either plated onto culture media, injected intradermally into immunodeficient mice, or into the human scar-forming skin xenografted onto immunodeficient mice.

Biography
Dr. Mimi (Maria) Rosealie Borrelli, MBBS, MSc, BSc, is currently working as a Postdoctoral Research Scholar in the Plastic and Reconstructive Surgery Department at Stanford University under the guidance of Dr. Michael T Longaker. Mimi has a Bachelor’s of Science in Experimental Psychology from the University of Bristol, where she passed with First Class Honors and was awarded ‘The Richard Gregory Prize’ for the most innovative final year dissertation. She also has a Master’s of Science in Cognitive Neuroscience with Distinction, and was awarded ‘The Shallice Prize’ for the best annual performance of her class. Mimi obtained her medical degree from King’s College London, graduating with three Distinctions and was awarded a Merit by the Associate of King’s College. Mimi has a strong interest in the cellular and molecular mechanisms of skin regeneration and scarring. Under the mentorship of Dr. Longaker at Stanford, she is developing strategies to manipulate fibroblast subpopulations and promote regenerative healing in the skin to minimize fibrosis. Her aspiration is to be a Plastic Surgeon-Scientist.