Department of Biochemistry Box 357350 University of Washington Seattle, WA 98195
 



 
 
 

         
David Russell         


Adjunct Professor of Biochemistry
Professor of Medicine (Hematology)
Investigator of the Markey Molecular Medicine Center

206.616.4562 V
drussell@u.washington.edu

 

Research

Dr. Russell's research program focuses on the development of improved methods for manipulating mammalian chromosomes, including transduction with viral vectors. The technologies being developed will find applications in somatic cell genetics, the engineering of mutant animals, and gene therapy.

Transduction by adeno-associated virus (AAV) vectors is an active area of investigation, including investigations on the mechanisms of AAV transduction, and the development of homologous gene targeting strategies based on AAV vectors, with the ultimate goal of therapeutic gene correction. Vectors based on other types of parvoviruses are also being developed, as these may have different host ranges or transduction mechanisms.

Vectors based on foamy viruses (an alternative retroviral vector system) are also being studied. Foamy virus vectors offer many advantages, such as improved transduction of stem cells, wide host range, and large packaging capacity. In addition to studies on the basic biology of foamy viruses, the potential of foamy virus vectors for gene therapy applications is being explored, including the development of improved vector production methods, and the testing of vectors in pre-clinical animal models. Recent findings from the group have shown that foamy virus vectors can efficiently transduce hematopoietic stem cells from animals and humans, suggesting that they will be useful in a variety of clinical applications.

A particular focus of the group is the genetic manipulation of stem cells. Experiments are underway with several different stem cell systems, including hematopoietic stem cells, mesenchymal stem cells, hepatic stem cells, and embryonic stem cells. The genetic manipulation of cells to be used for cloning by nuclear transfer is a related research interest, as is more recent work on in vivo cell fusion and nuclear reprogramming.


Selected Publications

Russell, D.W., and Hirata, R.K. (1998). Human gene targeting by viral vectors. Nat. Genet. 18: 325-330.

Rutledge, E.A., Halbert, C.L., and Russell, D.W. (1998). Infectious clones and vectors derived from adeno-associated virus (AAV) serotypes other than AAV type 2. J. Virol. 72: 309-319.

Vassilopoulos, G., Trobridge, G.D., Josephson, N., and Russell, D.W. (2001). Gene transfer into murine hematopoietic stem cells with helper-free foamy virus vectors. Blood 98: 604-609.

Hirata, R.K., Chamberlain, J.C., Dong, R., and Russell, D.W. (2002). Targeted transgene insertion into human chromosomes by adeno-associated virus vectors. Nat. Biotechnol. 20:735-738.

Josephson, N.C., Vassilopoulos, G., Trobridge, G.D., Priestley, G.V., Wood, B.L., Papayannopoulou, T., and Russell, D.W. (2002). Transduction of human NOD/SCID-repopulating cells with both lymphoid and myeloid potential by foamy virus vectors. Proc. Natl. Acad. Sci. USA 99:8295-8300.

Miller, D.G., Rutledge, E.A., and Russell, D.W. (2002). Chromosomal effects of adeno-associated virus vector integration. Nat. Genet. 30: 147-148.

Trobridge, G., Josephson, N., Vassilopoulos, G., Mac, J, and Russell, D.W. (2002). Improved foamy virus vectors with minimal cis-acting sequences. Mol. Ther. 6:321-328.

Hendrie, P.C., Hirata, R.K, and Russell, D.W. (2003). Chromosomal integration and homologous gene targeting by replication-incompetent vectors based on the autonomous parvovirus Minute Virus of Mice. J. Virol. 77:13136-13145.

Miller, D.G., Petek, L.M., and Russell, D.W. (2003). Human gene targeting by adeno-associated virus vectors is enhanced by DNA double strand breaks. Mol. Cell. Biol. 23:3550-3557.

Vassilopoulos, G., Wang, P., and Russell, D.W. (2003). Transplanted bone marrow regenerates liver by cell fusion. Nature 422:901-904.

Chamberlain, J.R., Schwarze, U., Wang, P., Hirata, R.K., Hankenson, K.D., Pace, J.M., Underwood, R.A., Song, K.M., Sussman, M., Byers, P.H., and Russell, D.W. (2004). Gene targeting in stem cells from individuals with osteogenesis imperfecta. Science 303:1198-1201.

Hirata, R.H., Xu, C., Dong, R., Miller, D.G., Ferguson, S., and Russell, D.W. (2004). Efficient PRNP gene targeting in bovine fibroblasts by adeno-associated virus vectors. Cloning Stem Cells 6:31-36.

Miller, D.G., Petek, L., and Russell, D.W. (2004). Adeno-associated virus vectors integrate at chromosome breakage sites. Nat. Genet. 36:767-773.

Hendrie PC, Russell DW (2005) Gene targeting with viral vectors. Mol Ther 12: 9-17.

Miller DG, Trobridge GD, Petek LM, Jacobs MA, Kaul R, Russell DW (2005) Large-scale analysis of adeno-associated virus vector integration sites in normal human cells. J Virol 79: 11434-11442.