Grants We Funded

Abstract
Long-term objectives Our objective is to understand the effects of c-Jun on moderating a fibroproliferative wound healing response in mouse and human skin. This work will advance our understanding on the key molecular and genetic changes within fibroblast subpopulations that are responsible for the formation of a scar. The long-term objective is to identify targetable fibrotic pathways within key dermal fibroblast subpopulations that can be manipulated to minimize scar formation and promote regenerative skin healing. Aim 1. To the explore the action of c-Jun overexpression in fibroblast subsets and infiltrating immune cells in a mouse model of inducible c-Jun overexpression Rationale: We have recently described a mouse model of inducible c-Jun overexpression and demonstrated how global c-Jun induction results in global tissue fibrosis. In aim 1, we will explore the effects of c-Jun overexpression in the setting of a cutaneous wound and explore specifically the role of c-Jun in distinct fibroblast subpopulations. Study design: c-Jun doxycycline-inducible mice and control mice will be wounded and the cells within the wound bed will be induced to overexpress c-Jun. Developing wounds will examined histologically to assess skin structure and fibrosis, and flow cytometry will be used to analyze the changes in abundance of certain fibrogenic sub-populations. RNA sequencing will be used to explore the effects of c-Jun overexpression on the gene expression within the fibroblast subpopulations in c-Jun, compared to control mice. Aim 2. To explore the role of c-Jun in human fibroblasts from normal and scarred skin Rationale: To explore the effects of c-Jun in moderating a fibroproliferative wound healing response in human skin, the effect of c-Jun deletion on functional activity of human skin fibroblasts will be studied. Human dermal fibroblasts will be derived from healthy control skin, scarred skin, hypertrophic scars, and keloids. A CRISPR-Cas9 method will be used to delete c-Jun, and the consequences of c-Jun deletion on fibroblast proliferation, apoptosis, and collagen production will be explored. RNA sequencing will be used to explore the effects of c-Jun deletion on the gene expression within the fibroblast with and without c-Jun.

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.