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Education and Training:

B.S. Biology, Massachusetts Institute of Technology, Cambridge, MA (1981)

Ph.D. Genetics, The Rockefeller University, New York, NY (1988)

M.D. Medicine, Cornell University Medical College, New York, NY (1989)

Internal Medicine Internship, New England Deaconess Hospital, Boston, MA (1989-90)

Internal Medicine Residency, New England Deaconess Hospital, Boston, MA (1990-91)

Fellow in Hematology, University of Washington School of Medicine, Seattle, WA (1991-94)

Fellow in Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA (1992-94)

David Russell, M.D., Ph.D.
Professor of Medicine
Division of Hematology
Adjunct Professor of Biochemistry
University of Washington School of Medicine

Office Address:
University of Washington Medical Center
Division of Hematology, Box 357720
1959 NE Pacific Street, HSB K-236A
Seattle, WA 98195-7720

Phone:  (206) 616-4562
Fax:      (206) 616-8298
E-mail:  drussell@u.washington.edu
Russell lab:  http://depts.washington.edu/dwrlab/

CURRENT CLINICAL INTERESTS

General hematology/oncology, gene therapy, osteogenesis imperfecta, stem cell transplantation, regenerative medicine


CURRENT RESEARCH INTERESTS


Stem cells, HLA engineering, viral vectors, gene therapy, gene editing


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 Genetic Medicine Center at the University of Washington in Seattle.

Dr. Russell’s 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, mammalian genetics, and regenerative medicine.

Adeno-Associated Virus (AAV) vectors are under investigation, including research on transduction mechanisms, chromosomal integration, and the development of gene editing vectors that introduce precise sequence changes at homologous chromosomal loci. One goal of these studies is to carry out therapeutic gene editing in human cells to treat genetic diseases. This approach is being applied towards the treatment of Osteogenesis Imperfecta (Brittle Bone Disease), and Severe Combined Immunodeficiency (X-SCID). AAV-mediated gene targeting is also being used to engineer human pluripotent stem cells with improved engraftment potential by precise editing of HLA genes. These ”universal donor cells” can be used in many regenerative medicine applications. In addition, our laboratory has used gene editing to model human diseases, including Down Syndrome and hepatocellular carcinoma.

Vectors based on Foamy Viruses (a type of retrovirus) are another research interest. These vectors offer many advantages, such as a lack of pathogenicity, efficient transduction of stem cells, wide host range, large packaging capacity, and a reduced likelihood of activating neighboring oncogenes after integration. 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 cure a canine form of leukocyte adhesion deficiency (LAD) by stem cell gene therapy and a human clinical trial for LAD is currently planned.

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 pluripotent stem cells. We are designing new vectors and transducing a variety of cell types to generate induced pluripotent stem cells. By efficiently introducing genetic changes into stem cells, basic aspects of stem cell biology are being addressed, including studies on developmental potential, transplantation, immune rejection, and epigenetics.


SELECTED PUBLICATIONS

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

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

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.

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

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. PMC296056

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.

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

Miller, D.G., Wang, P., Petek, L.M., Hirata, R.K., Sands, M.S., and Russell, D.W. (2006). Gene targeting in vivo by adeno-associated virus vectors. Nat. Biotechnol. 24:1022-1026.

Donsante, A., Miller, D.G., Li, Y., Vogler, C., Brunt, E.M., *Russell, D.W., and *Sands, M.S. (2007). AAV vector integration sites in mouse hepatocellular carcinoma. Science 317:477. (*co-corresponding authors)

Bauer, T.R., Allen, J.M., Hai, M., Tuschong, L.M., Khan, I.F., Olson, E.M., Adler, R.L., Burkholder, T.H., Gu, Y., *Russell, D.W., and *Hickstein, D.D. (2008). Successful treatment of canine leukocyte adhesion deficiency by foamy virus vectors. Nat. Med. 14:93-97 (*co-corresponding authors).

Khan, I.F., Hirata, R.K., Wang, P., Li, Y., Kho, J., Nelson, A., Huo, Y., Zavajlevski, M., Ware, C., and Russell, D.W. (2010). Engineering of human pluripotent stem cells by AAV-mediated gene targeting. Mol. Ther. 18:1192-1199. PMC2889726

Deyle, D.R., Khan, I.F., Ren, G., Wang, P.R., Kho, J., Schwarze, U., and Russell, D.W. (2012). Normal collagen and bone production by gene-targeted human Osteogenesis Imperfecta iPSCs. Mol. Ther. 20:204-213. PMID: 22031238

Wang, P.R., Xu, M., Toffanin, S., Li, Y., Llovett, J.M., and Russell, D.W. (2012). Induction of hepatocellular carcinoma by in vivo gene targeting. Proc. Natl. Acad. Sci. USA. 109:11264-11269.

Li, L.B., Chang, K.H., Wang, P.R., Hirata, R.K., Papayannopoulou, T., and Russell, D.W. (2012). Trisomy correction in Down syndrome induced pluripotent stem cells. Cell Stem Cell 11:615-619.

Riolobos, L., Hirata, R.K., Turtle, C.J., Wang, P.R., Gornalusse, G.G., Zavajlevski, M., Riddell, S.R., and Russell, D.W. (2013). HLA engineering of human pluripotent stem cells. Mol. Ther. 21:1232-1241.