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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, 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 Genetic Medicine Center at the University of Washington in Seattle.

Dr. Russellís 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 pluripotent stem cells with improved engraftment potential.

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 oncogens 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 plutipotent 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, recombination, and nuclear reprogramming.

rincipal 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.

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.

Khan IF, Hirata RK, Wang P, Li Y, Kho J, Nelson A, Huo Y, Zavajlevski M, Ware C, and Russell DW.  Engineering of human pluripotent stem cells by AAV-mediated gene targeting. Mol. Ther. 18:1192-1199, 2010.

Deyle, DR, Li, Y, Olson, EM, and Russell, DW. Non-integrating foamy virus vectors. J. Virol. 84:9341-9349, 2010.