Curriculum Vitae

Cellular, Tissue and Gene Therapies Advisory Committee

NAME Chamberlain, Jeffrey S .	POSITION TITLE Professor
eRA COMMONS USER NAME chamberl	POSITION TITLE Professor
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION	DEGREE (if applicable)	YEAR(s)	FIELD OF STUDY
Rice University, Houston, Texas University of Washington, Seattle, Washington Baylor College of Medicine, Houston, Texas	B.S. Ph.D. Post Doc	1978 1985 1990	Biochemistry Biochemistry Molecular Genetics

Professional Positions:

1990-1994
1994-1999
1999-2000
1999-2000
2001-
2002-
2003-

Assistant Professor, Dept. of Human Genetics, U. Michigan Medical School, Ann Arbor, MI.
Associate Professor, Department of Human Genetics, U. Michigan Medical School, Ann Arbor, MI
Interim Director, Center for Gene Therapy, U. Michigan Medical School, Ann Arbor, MI
Professor, Dept. of Human Genetics, U. Michigan Medical School, Ann Arbor, MI
Professor, Dept. of Neurology, University of Washington School of Medicine, Seattle, WA
Professor, Dept. of Medicine, Division of Medical Genetics, University of Washington
Professor, Dept. of Biochemistry, University of Washington

Awards and Other Professional Activities:
1991 1992- 1994 1995 1995- 1996- 1999-2002 2000-2005 2001 2002 2002- 2003-2006 2004 2005-	Basil O’Conner Starter Scholar Research Award, March of Dimes Birth Defects Foundation Policy and Monitoring Board, NIH NHLBI ‘Collaborative Studies on the Genetics of Asthma’ Leadership Award, Service Merchandise Inc. Gift of Hope Award, Jones Intercable Inc. Scientific Advisory Committee, Muscular Dystrophy Association Scientific Review Board, National Gene Vector Laboratory Board of Directors, American Society of Gene Therapy Biological Response Modifiers Advisory Committee, CBER, FDA, ad hoc member Advisory committee on skeletal muscle biology, NIH, CSR Special emphasis review panels (4), chair, NIH Muscular dystrophy task force member, NIH Translational Research Advisory Committee member, Muscular Dystrophy Association Skeletal muscle and exercise physiology study section, NIH, ad hoc member Cellular, Tissue and Gene Therapies Advisory Committee, Center for Biologics Evaluation and Research, FDA
Editorial Boards: Gene Therapy , Human Gene Therapy, Neuromusc Disorders, J Gene Med, Molec Therapy

Publications (from >150)

Chamberlain JS, Jaynes JB and Hauschka SD: Regulation of creatine kinase induction in differentiating mouse myoblasts. Mol Cell Biol 1985;5:484-492.

Chamberlain JS, Pearlman JA, Muzny DM, Gibbs RA, Ranier JE, Reeves AA and Caskey CT: Expression of the murine Duchenne muscular dystrophy gene in muscle and brain. Science 1988; 239:1416-18.

Chamberlain JS, Gibbs RA, Ranier JE, Nguyen PN and Caskey CT: Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res 1988; 16:11141-56.

Lee CC, Pearlman JA, Chamberlain JS, and Caskey CT: Expression of recombinant dystrophin and its localization to the cell membrane. Nature 1991; 349:334-336.

Chamberlain JS, Chamberlain JR, Fenwick RG, et al.: Diagnosis of Duchenne and Becker muscular dystrophies by polymerase chain reaction: A multicenter study. JAMA 1992; 267:2609-2615.

Cox GA, Phelps SF, Chapman VM, Chamberlain JS: New mdx mutation disrupts expression of muscle and nonmuscle isoforms of dystrophin. Nature Genet 1993: 4:87-93.

Cox GA, Cole N, Matsamura K, Phelps SF, Hauschka SD, Campbell KP, Faulkner JA, Chamberlain JS: Overexpression of dystrophin in transgenic mdx mice eliminates dystrophic symptoms without toxicity. Nature 1993; 364:725-729.

Cox GA , Sunada Y, Campbell KP, Chamberlain JS: Dp71 can form a stable dystrophin-associated glycoprotein complex in muscle but fails to prevent dystrophy. Nature Genet 1994; 8:333-338.

Phelps SF, Hauser MA, Cole NM, Rafael JA, Hinkle RT, Faulkner JA, Chamberlain JS: Expression of full-length and truncated dystrophin mini-genes in transgenic mdx mice. Hum Mol Genet 1995; 4:1251-1258.

Kumar-Singh R, and Chamberlain JS: Encapsidated adenovirus minichromosomes allow delivery and expression of a 14 kb dystrophin cDNA to muscle cells. Hum Mol Genet 1996; 5:913-922.

Rafael JA, Cox GA, Jung D, Campbell KP, and Chamberlain JS: Forced expression of dystrophin deletion constructs reveals structure-function correlations. J Cell Biol. 1996; 134:93-102.

Amalfitano A and Chamberlain JS: Isolation of packaging cell lines that co-express the adenovirus E1, DNA polymerase and preterminal proteins: implications for gene therapy. Gene Ther 1997; 4:258-263.

Corrado K, Rafael J, Mills P, Cole N, Faulkner J, Wang K, and Chamberlain J: Transgenic mice expressing a dystrophin gene with a deletion in the actin-binding domain display a “mild Becker” phenotype. J Cell Biol. 1996; 134:873-884.

Straub V, Rafael J, Chamberlain J, and Campbell K. Animal models of muscular dystrophy show different patterns of sarcolemmal disruption. J Cell Biol 1997;139:375-385.

Amalfitano A, Hauser MA, Serra D, Begy C, and Chamberlain JS: Isolation and characterization of improved adenoviral vectors deleted for the E1, E2b, and E3 genes. J Virol 1998; 72:926-33.

Lumeng CN, Phelps SF, Rafael JA, Cox GA, Hutchinson TL, Begy CR, Adkins E, Wiltshire R, and Chamberlain JS: Characterization of dystrophin and utrophin diversity in the mouse. Hum Mol Genet, 1999; 8:593-599.

Lumeng CN, Phelps SF, Hutchinson TL, Walden P, and Chamberlain JS: Interaction of b2 syntrophin with a family of microtubule associated serine/threonine kinases. Nature Neurosci 1999; 7:611-617.

Hartigan-O'Connor DJ, Amalfitano A, Chamberlain JS. Improved production of gutted adenovirus in cells expressing adenovirus preterminal protein and DNA polymerase. J Virol 1999, 73:7835-7841.

Chamberlain JS. The dynamics of dystroglycan. Nature Genet 1999, 23: 256-258.

Hauser M, Robinson A, Hartigan-O’Connor D, Williams-Gregory D, Buskin J, Apone S, Kirk C, Hardy S, Hauschka S, and Chamberlain J: Analysis of muscle creatine kinase regulatory elements in recombinant adenoviral vectors. Mol Ther 2000; 2:16-25.

Crawford GE, Faulkner J, Crosbie R, Campbell K, Froehner S, and Chamberlain J: Assembly of the dystrophin associated protein complex does not require the dystrophin COOH-terminal domain. J Cell Biol 2000; 150:1399-1410.

Lynch GS, Rafael JA, Chamberlain JS, and Faulkner JA: Contraction-induced injury to single permeabilized muscle fibers from mdx, transgenic mdx, and control mice. Am J Physiol (Cell Physiol) 2000; 279: C1290-C1294.

Hodges BL, Serra D, Huimin H, Begy C, Chamberlain JS and Amalfitano A: Multiply deleted [E1, polymerase-, and pTP-] adenovirus vector persists despite deletion of the preterminal protein. J Gene Med 2000; 2:250-259.

Lynch GS, Hinkle RT, Chamberlain JS, Brooks SV and Faulkner JA: Force and power output of fast and slow skeletal muscles from young, adult and old mdx mice. J. Physiol ( London) 2001; 591-600.

Hartigan-O'Connor D, Kirk C, Crawford R, Mule J, and Chamberlain JS: Immune evasion by muscle specific gene expression in dystrophic muscle. Mol Ther 2001, 4:525-533.

Hartigan-O'Connor D, Barjot C, Crawford R, and Chamberlain JS: Efficient rescue of gutted adenovirus genomes allows rapid production of concentrated stocks without negative selection. Hum Gene Ther 2002; 13:519-531.

Warner L, DelloRusso C, Crawford R, Rybakova I, Patel I, Ervasti J, and Chamberlain JS. Expression of Dp260 in muscle tethers the actin cytoskeleton to the dystrophin-glycoprotein complex. Hum Mol Genet 2002; 11:1095-1105.

Barjot C, Hartigan-O’Connor D, Salvatori G, Scott JM, and.Chamberlain JS: Gutted adenoviral vector growth using E1/E2b/E3-deleted helper viruses. J Gene Med 2002, 4:480-489.

Harper S, Crawford R, DelloRusso C, and Chamberlain JS: Spectrin-like repeats from dystrophin and a-actinin-2 are not functionally interchangeable. Hum Mol Genet; 11:1807-1815.

Hartigan-O'Connor D, Barjot C, Salvatori G, and Chamberlain JS: Generation and growth of gutted adenoviral vectors. Methods Enzymol 2002; 346:224-246.

Harper S, Hauser M, DelloRusso C, Duan D, Crawford RW, Phelps SF, Harper HA, Robinson AS, Engelhardt JF, Brooks SV, and Chamberlain JS. Modular flexibility of dystrophin: Implications for gene therapy of Duchenne muscular dystrophy. Nature Med 2002; 8:253-261.

Chamberlain JS. Gene therapy of muscular dystrophy. Hum Mol Genet 2002; 11:2355-2362.

DelloRusso C, Scott J, Hartigan-O’Connor D, Salvatori G, Barjot C, Robinson A, Crawford R, Brooks S, and Chamberlain J: Functional correction of adult mdx mouse muscle using gutted adenoviral vectors expressing full-length dystrophin; Proc Nat’l Acad Sci (USA) 2002; 99:12979-12984.

Gregorevic , P and Chamberlain J. Gene therapy for muscular dystrophy. Expert Opin Biol Ther 2003; 3:803-814.

Ge Y, Molloy M, Chamberlain J, and Andrews P. Tracking the pathophysiology of DMD with proteomics: adenylate kinase 1 (AK 1) is greatly reduced in skeletal muscle from mdx mice. Proteomics 2003; 3:1895-1903.

Friedrich O, Gillis JM, Chamberlain JS, and Fink RHA: Mini-dystrophin restores L-type calcium currents in transgenic mdx mice. J Physiol 2004; 555: 251-265.

Abmayr S, Crawford R and Chamberlain JS: Characterization of ARC, apoptosis repressor interacting with CARD, in normal and dystrophin-deficient skeletal muscle. Hum Molec Genet 2004; 13:213-221.

Yue, Y., Li, Z., Harper, S.Q., Davisson, R.L., Chamberlain, J.S. and Duan, D. Microdystrophin gene therapy of cardiomyopathy restores dystrophin-glycoprotein complex and improves sarcolemma integrity in the mdx mouse heart. Circulation 2003; 108: 1626-1632.

Blankinship M, Gregorevic P, Allen J, Harper S, Harper H, Halbert C, Miller A and Chamberlain J. Efficient transduction of skeletal muscle using vectors based on adeno-associated virus serotype 6. Mol Ther 2004; 10:671-678.

Bachrach E, Li S, Perez AL, Schienda J, Liadaki K, Volinski J, Flint A, Chamberlain JS, And Kunkel LM: Systemic delivery of human microdystrophin to regenerating mouse dystrophic muscle by muscle progenitor cells. Proc Nat’l Acad Sci ( USA) 2004; 101:3581-3586.

Gregorevic P, Blankinship MJ, Allen J, Crawford RW, Meuse L, Miller D, Russell DW and Chamberlain JS: Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nature Med 2004; 10:828-834.

Liu M, Yue Y, Harper SQ, Grange RW, Chamberlain JS and Duan D: Adeno-associated virus-mediated micro-dystrophin expression protects young mdx muscle from contraction-induced injury. Mol Ther 2005; 11:245-256.

Li S, Kimura E, Reyes M, Angello JC, Welikson R, Hauschka SD and Chamberlain JS: Stable transduction of myogenic cells with lentiviral vectors expressing a mini-dystrophin. Gene Therapy 2005; 12: 1099-1108.

Balcaitis S, Weinstein JR, Li S, Chamberlain JS and Moeller T: Lentiviral transduction of microglial cells. Glia 2005; 50:48-55.

Abmayr S, Gregorevic P, Allen JM and Chamberlain JS: Enhanced muscle recovery following co-delivery of micro-dystrophin and Igf-1 to adult mdx muscles. Mol Ther 2005; 12:441-450.

Reyes M, Li S, Kimura E, and Chamberlain JS: Donor origin of multipotent adult progenitor cells in radiation chimeras. Blood 2005; 106:3646-3649.

Lai Y, Yue Y, Liu M, Ghosh A, Engelhardt JF, Chamberlain JS, Duan D: Rescue of muscular dystrophy in mdx mice by trans-splicing adeno-associated virus-mediated ∆H2-R19 mini-dystrophin expression. Nat Biotech 2005; 23:1435-1439.

Blankinship M, Gregorevic P and Chamberlain JS: Gene therapy strategies for Duchenne muscular dystrophy utilizing recombinant adeno-associated virus vectors. Mol Ther 2006; 13:241-249.

Judge L, Haraguchi M and Chamberlain JS: Dissecting the signaling and mechanical functions of the dystrophin-glycoprotein complex. J Cell Sci 2006; in press.

Other Research Support
R37 AR40864	Chamberlain (PI)	04/01/1991 – 03/31/2010
NIH Dystrophin replacement in mdx mice The goals of this project are to generate and analyze dystrophin transgenic mouse models for muscular dystrophy related to exploration of the function of dystrophin and the feasibility of gene therapy for DMD. Role: PI

R01 AR44533	Chamberlain (PI)	04/01/1996 – 03/31/2007
NIH Assembly of the dystrophin associated protein complex The goals of this project are to examine the relationship between defective assembly of the dystrophin-glycoprotein complex (DGC) and the mechanical, signaling, and immune-mediated mechanisms of muscle fiber destruction. Role: PI

PO1 AG015434	Metzger (PI)	05/01/1998 – 04/30/2008
NIH Genetic modifications of striated muscles during aging Project 1: Modified Adenoviral Vectors for Gene Transfer to Muscle Agency: NIH This is a program project grant to study gene transfer in aging muscle. Project 1 is to develop E2b-deleted and helper-dependent or ‘gutted’ adenoviral vectors and to explore their immunology in muscle; and additional aim is to explore new AAV serotypes for gene transfer to diseased and aging muscles. Role: PI of Project 1

U54 AR050741-01	Chamberlain (PI)	09/26/2003-08/31/2008
NIH Muscular Dystrophy Cooperative Research Center This is a cooperative research center focused on conducting pre-clinical studies leading to a phase 1 clinical trial of gene therapy for DMD using adeno-associated viral vectors. I am the Center Director, as well as PI of project 1, which proposes to conduct pre-clinical studies in mice using intramuscular injection of rAAV6/micro-dystrophin. I am also PI of Core B, a viral vector core lab that will make cGMP-grade AAV6 vectors for this Center, and which will make non-GMP vectors for other muscle labs. Role: Center Director, PI of Project 1 and co-PI of Core B (Viral Vector Core).

MDA Supplementary Grant	Chamberlain (PI)	01/01/2004 - 12/31/2007
Muscular Dystrophy Cooperative Research Center Supplement MDA supplement to the NIH MDCRC (previous grant on this list). Role: PI of Project 1 and co-PI of Core B (Viral Vector Core).

P01 AS046788-01	Froehner (PI)	04/01/2004-03/31/2009
NIH Molecular and cellular therapies for muscular dystrophy Project 1: Dystrophin delivery to muscle via myogenic precursors This is a program project application to explore therapeutic options for the muscular dystrophies. Project 1 explores the use of stem cells for ex vivo gene therapy of muscular dystrophy. Role: PI of Project 1 and of Core B, Animal Physiology Core.