CURRENT CLINICAL
INTERESTS
General hematology/oncology, gene therapy, osteogenesis imperfecta,
stem ell transplantation, regenerative medicine
CURRENT RESEARCH INTERESTS
Stem cells, viral vectors, gene therapy, genetic recombination
RESEARCH DESCRIPTION
Principal Investigator: Dr. Russell is a Professor in the Department of Medicine
(Division of Hematology), Adjunct in the Department of Biochemistry, and an Investigator of the Markey Molecular Medicine
Center at the University of Washington in Seattle.
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 osteogenesis imperfecta (brittle bone disease) by targeting mutant collagen genes in bone-forming mesenchymal stem cells.
Vectors based on foamy viruses (an alternative retroviral vector system) are also a research interest. These vectors offer many advantages, such as improved transduction of stem cells, wide host range, and large packaging capacity, making them a promising vector for gene therapy. Ongoing projects include the development of improved vector production methods, mapping and analysis of vector integration sites, and the testing of vectors 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.
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.
SELECTED PUBLICATIONS
Russell DW and Hirata RK: Human gene targeting by viral vectors.
Nat. Genet. 18:325-330, 1998.
Hirata RK, Chamberlain JC, Dong R, and Russell
DW. Targeted transgene insertion into human chromosomes by adeno-associated virus vectors. Nat. Biotechnol.
20:735-738, 2002.
Vassilopoulos G, Wang P, and Russell DW.
Transplanted bone marrow regenerates liver by cell fusion. Nature 422:901-904, 2003.
Chamberlain JR, Schwarze U, Wang P, Hirata RK, Hankenson KD, Pace JM, Underwood RA, Song KM, Sussman M, Byers PH, and
Russell DW. Gene targeting in stem cells from individuals with osteogenesis imperfecta. Science 303:1198-1201, 2004.
Miller DG, Petek L, and Russell DW.
Adeno-associated virus vectors integrate at chromosome breakage sites.
Nat. Genet. 36:767-773, 2004.
Miller DG, Wang P, Petek LM, Hirata RK, Sands MS, and
Russell DW. Gene targeting in vivo by adeno-associated virus vectors. Nat. Biotechnol. 24:1022-1026, 2006.
Donsante A, Miller DG, Li Y, Vogler C, Brunt EM, Russell
DW, and Sands MS. AAV vector integration sites in mouse hepatocellular carcinoma. Science 317:477, 2007.
Gharwan H, Hirata RK, Wang P, Richard RE, Wang L, Olson E, Allen J, Ware CB, and
Russell DW. Transduction of human embryonic stem cells by foamy virus vectors. Mol. Ther.
15:1827-1833, 2007.
Bauer TR, Allen JM, Hai M, Tuschong LM, Khan IF, Olson EM, Adler RL, Burkholder TH, Gu Y,
Russell DW, and Hickstein DD. Successful treatment of canine leukocyte adhesion
deficiency by foamy virus vectors. Nat. Med. 14:93-7, 2008.
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