Research in the laboratory of David R. Deyle, M.D., is aimed at developing gene and cell therapies for the treatment of genetic disorders through the correction and alteration of the genome in human stem cells. Dr. Deyle and colleagues are working on improved methods of targeted genomic editing using viral vectors for the precise alteration of the human genome. His research team focuses on the genetic modification of mesenchymal stem cells and induced pluripotent cells (iPSCs) and on defining molecular mechanisms that control stem cell differentiation for the regeneration of skeletal tissue. In addition, the team is developing oncolytic viral therapy using measles virus for the treatment of neurofibromatosis 1 (NF1) tumors.
- Genomic editing. Dr. Deyle's laboratory focuses on developing adeno-associated virus (AAV) gene targeting, transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) genomic editing technologies for the treatment of genetic disorders. His team is studying how these approaches may be utilized in tissue culture and in the human body to specifically modify the human genome in stem cells.
- Gene and cell therapy to treat osteogenesis imperfecta. Brittle bone disease (osteogenesis imperfecta, or OI) is a common inherited bone disorder that leads to fractures and other nonskeletal manifestations. Dr. Deyle's team is developing new treatment strategies for OI using iPSC and gene therapy approaches.
- In vivo modeling of genetic skeletal disease. Alterations in bone homeostasis can affect the integrity of bone and also other tissue. Dr. Deyle's group has developed a mouse model that will allow for the monitoring of stem cell fate in vivo and the effects of corrected stem cells on bone biology and other tissues.
- Development of measles virus therapy to treat NF1 tumors. Neurofibromatosis 1 is a genetic disorder that affects one in 3,000 individuals worldwide and leads to the development of nerve sheath tumors. Dr. Deyle's laboratory is testing a measles virus, MV-NIS, as a novel therapeutic agent to treat tumors that arise in patients with NF1.
Significance to patient care
The long-term goal of Dr. Deyle's research is to develop novel therapeutics for the treatment of genetic disorders. Corrected or modified human stem cells will be of particular importance in the development of regenerative medicine therapies, and the knowledge that is gained from understanding and treating genetic disorders can be applied to other more common diseases.
In addition, individuals with NF1 have very limited options for treatment of their tumors. The use of oncolytic viruses to inhibit or regress tumor growth is a novel therapy that has the potential to dramatically alter the treatment options for NF1 patients.