The Carl J. Shapiro Department of Orthopaedic Surgery invites you to the Wilson C. Hayes Distinguished Lecture Series on Musculoskeletal Heath on May 3, 2023 at 8AM EST. Click here to view the lecture flyer and Zoom link.
ENGINEERING THE GENOME TO DEVELOP NEW BIOLOGIC THERAPIES FOR ARTHRITIS
FASRSHID GUILAK, PHD
Mildred B. Simon Research Professor of Orthopaedic Surgery
Department of Orthopaedic Surgery, Washington University in St. Louis
Shriners Hospitals for Children, St. Louis
Arthritis represents a painful and debilitating family of joint diseases that is characterized by progressive degeneration of the articular cartilage; however, there are currently few disease-modifying treatments available. Our lab has focused on tissue engineering approaches for resurfacing entire joints using adult stem cells and biomimetic 3D woven fiber scaffolds. Furthermore, we have used combinations of gene therapy and tissue engineering to develop tissue replacements that possess the capability for biologic drug delivery. In recent years, the advent of synthetic biology and gene-editing methods such as CRISPR-Cas9 has allowed for precise modifying gene networks that control cell behavior. We have applied a combination of principles from these fields to rewire cellular gene circuits in stem cells in a manner that allows us to create a unique, custom-designed cell type that can sense and respond to its biochemical environment in a pre-programmed way. These cells have been used to develop engineered tissue replacements with the ability for tunable, inducible, or feedback-controlled, auto-regulated biological responses. Using this approach, we have recently developed synthetic “mechanogenetic” gene circuits that express therapeutic transgenes in response to defined mechanical signals. In addition to recapitulating the biochemical and biomechanical properties of the tissue, these “smart” cells and constructs can provide controlled drug delivery and immunomodulatory responses to the joint as therapies for cartilage repair or arthritis.