Regulation of Type VII Collagen in Patients with Recessive Dystrophic Epidermolysis Bullosa

Abstract

Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a complex, life-threatening genetic skin disorder with painful complications. Currently, there is no cure, but there have been recent developments in both the basic biological research aspects and the translational therapies which make effectively treating this disease more likely in the near future. These advances include the use of stem cells and gene editing as well as new insights into the molecular mechanisms for certain aspects of RDEB pathology. The overall goals of our lab are to better define and characterize RDEB pathology, develop novel approaches for treating RDEB, and to improve upon the ways in which we analyze and understand the outcomes of those therapies. These goals are inherently dependent upon a comprehensive understanding of how type VII collagen is regulated, both during the normal wound healing process and over the course of therapeutic intervention. To that aim, we set out to understand two aspects of regulation of type VII collagen that were poorly understood: one focused on the nature of type VII collagen regulation during wound healing and the other focused on type VII collagen regulation during the hematopoietic stem cell transplantation process. We identified a particular micro RNA, miR-29, which regulates COL7A1 transcriptionally and post-transcriptionally. We also demonstrated that fludarabine, a key component of the hematopoietic cell transplantation (HCT) preparative regimen, modulates type VII collagen expression during hematopoietic stem cell transplantation. Our studies have identified a novel mechanism of regulation for type VII collagen that will hopefully give valuable insight into how to treat RDEB, ameliorate RDEB pathology, and properly evaluate clinical outcomes in patients that have receive HCT to treat RDEB.