Grants We Funded

Abstract
Aberrations in the tightly regulated biological process of wound healing can lead to disfiguring hypertrophic scars. Myofibroblasts in the dermis play a central role in hypertrophic scar formation by expressing excessive amounts of extracellular matrix and promoting robust tissue contraction. Studies in recent years have focused on the roles of mechanical force and TGF-beta in promoting myofibroblast differentiation. However, little is known about how paracrine mediators secreted by epidermal keratinocytes modulate myofibroblast differentiation, in vitro and in vivo. Integrins are the major family of extracellular matrix receptors, and they play critical roles in both cell adhesion and regulation of paracrine communication between different cellular compartments of the skin. Previous studies by our co-investigators have identified two integrins on epidermal keratinocytes that play critical roles in scar formation and the fibrotic phenotype. We hypothesize that interrupting this integrin-dependent crosstalk between epidermal keratinocytes and dermal myofibroblasts will reduce hypertrophic scar formation. Several previously developed transgenic mouse lines with epidermis-specific knockout of these key integrins will be used. Incisional wounds will be created on the backs of both transgenic and wild type mice and then hypertrophic scarring will be induced using an established mechanical loading device. This device is necessary to overcome the loose-skinned nature of rodents, and to induce mechanical tension such that the mechanical microenvironment of the wound is similar to that seen in humans. Proteomics, immunohistology, and other techniques will be used to identify putative targets that are critical to crosstalk from epidermal keratinocytes to myofibroblasts in the dermis. The proposed studies hold great promise to uncover key targets for the development of novel therapeutic agents to prevent or reverse hypertrophic scar formation.

Biography
Paschalia (Lina) Mountziaris was born in Princeton, NJ. She earned a B.S.E. from Princeton University in 2005, graduating magna cum laude with high departmental honors in Chemical Engineering and dual minor degrees in Engineering Biology and French Literature. She was subsequently recruited by the Baylor College of Medicine and Rice University Medical Scientist Training Program and earned a Ph.D. degree in Bioengineering (2011) and an M.D. (2012). Her doctoral dissertation research on “Harnessing Inflammatory Signaling to Promote Bone Regeneration and Mitigate Joint Damage” was supervised by Professor Antonios G. Mikos, a Member of the National Academy of Medicine and the National Academy of Engineering. After completing a postdoctoral research appointment in Bioengineering at Rice, she became an Integrated Plastic Surgery Resident at Albany Medical Center in 2013. Dr. Mountziaris is the author of 18 peer-reviewed publications and has received several awards for her research and academic accomplishments, including the Mary F.D. Morse Graduate Fellowship for Academic Achievement and Excellence in Healthcare-Related Research, the 2012 Outstanding Ph.D. Thesis Award in Bioengineering from Rice University and the 2012 Award for Outstanding Ph.D. Research from the Society for Biomaterials.