April Craft’s lab studies the development of cartilage and other synovial joint tissues, with hopes of applying this knowledge toward the development of therapeutics for disease attenuation and tissue regeneration and repair.
Research in the Craft Lab
Our research focuses on both developmental biology and translational medicine, and involves the use of pluripotent stem cells to understand how musculoskeletal lineages, primarily articular chondrocytes and cartilage tissues, are specified during embryonic development and how mature cells and tissues are maintained or regenerated after birth and in the adult. The goal is to apply this knowledge towards the development of improved therapeutics for skeletal diseases including congenital joint disorders and arthritis.
Degenerative joint disease, also known as osteoarthritis, is among the top five most costly medical conditions in the Unites States. One of the challenges of repairing the articular cartilage that lines our joints is that this tissue forms prenatally, and regeneration does not normally occur after birth.
We hypothesize that a better understanding of how joint tissues arise during embryonic development will enable us to develop better approaches for treating damaged joint tissues in patients.
By providing developmental signals that mimic how cartilage is specified in the embryo, our lab has developed methods that enable us to reproducibly and efficiently generate two distinct cartilage lineages from human embryonic stem cells and induced pluripotent stem cells (collectively hPSCs). One chondrocyte lineage has the ability to generate stable cartilage in vivo (a function of articular cartilage) and the other produces a cartilaginous tissue that undergoes ossification (a function of growth plate cartilage to form new bone). Our efforts are now focused on further understanding how these different types of cartilage are specified and how they are maintained in the adult.
Damage to articular cartilage can occur for a number of reasons (e.g., joint injury, mechanical instability, genetic predisposition). Because many patients do not feel pain during the early stages of degeneration, progressive deterioration of the cartilage ensues. Thus, the impact of these factors and others on cartilage health is difficult to assess. Our approach to identify early cartilage-specific changes that can result in progressive degeneration and disease takes advantage of our ability to generate articular cartilage tissues from hPSCs.
In a proof-of-principle experiment, we observed pathologically relevant catabolic changes in hPSC-derived articular cartilage in response to environmental stresses, such as the pro-inflammatory cytokines found in arthritic joints. Furthermore, the use of cartilage derived from patient-specific iPSCs will be invaluable to understand the genetic basis of disease mechanisms.
April Craft received her B.S. cum laude from Westminster College (PA) and her Ph.D. from the University of Pittsburgh School of Medicine. Her graduate research was performed in the gene therapy-based laboratory of Dr. Joseph Glorioso where she engineered non-toxic viral vectors suitable for gene expression in stem cells, and developed viral replication-based functional genomics platforms to screen for genes that activate developmental programs. In Dr. Gordon Keller’s lab at the McEwen Centre for Regenerative Medicine in Toronto, Dr. Craft initiated a successful cartilage research program as a post-doctoral fellow.