Our research program focuses on the development of improved methods for manipulating mammalian genomes in living cells. The technologies being developed have applications in stem cell biology, gene therapy, and somatic cell genetics.

Adeno-Associated Virus (AAV) vectors are under investigation, including research on transduction mechanisms, chromosomal integration, and the development of gene targeting vectors that introduce precise sequence changes at homologous chromosomal loci. One goal of these studies is to carry out therapeutic gene targeting in human cells to treat genetic diseases. This approach is being applied towards the treatment of osteogenisis imperfecta (brittle bone disease) by targeting mutant collagen genes in bone-forming mesenchymal stem cells. AAV-mediated gene targeting is also being used to engineer human embryonic stem cells with improved engraftment potential.

Vectors based on Foamy Viruses (an alternative retroviral vector system) are another research interest. These vectors offer many advantages, such as a lack of pathogenicity, efficient transduction of stem cells, wide host range, and large packaging capacity. Ongoing projects include the development of improved vector production methods, analyzing the effects of vector integration, and testing in pre-clinical animal disease models. Recent work has shown that Foamy Virus vectors can efficiently transduce hematopoietic stem cells from mice, dogs, and humans. Vectors are being developed for the treatment of leukocyte adhesion deficiency and AIDS.

A particular focus of the laboratory is the genetic manipulation of stem cells. Experiments are underway with hematopoietic stem cells, mesenchymal stem cells, hepatic stem cells, and embryonic stem cells. The genetic manipulation of cells used for cloning by nuclear transfer is a related research interest. By efficiently introducing genetic changes into stem cells, basic aspects of stem cell biology are being addressed, including studies on developmental potential, transplantation, cell fusion, and nuclear reprogramming.