Joel Chamberlain
Research Associate Professor
Medical Genetics

Faculty Information


Joel Chamberlain moved to the University of Washington in 2001 from the University of Michigan Medical School where she had completed graduate training in Cell and Molecular Biology in the laboratory of Dr. David Engelke (Biological Chemistry).  Her postdoctoral training at UW in the laboratory of Dr. David Russell (Hematology) culminated in a first authored manuscript in Science detailing gene targeting using adeno-associated viral vectors (AAV) for dominant bone disease therapy development.  Gene targeting was developed to eliminate the mutant collagen gene in mesenchymal stem cells from individuals with the Brittle Bone disease osteogenesis imperfecta.  As a faculty member in the Division of Medical Genetics in the Department of Medicine at UW Joel Chamberlain has developed a gene therapy research program aimed at treating dominantly inherited muscle disorders.  Her approach is based on RNA interference methods using AAV-mediated muscle delivery for the most common adult muscular dystrophies, myotonic dystrophy (DM) and facioscapulohumeral dystrophy (FSHD).  She is also studying FSHD in both patient muscle biopsies and a tunable mouse model developed in her laboratory.

Education & Training: 
Tulane University
Ph.D., Cellular and Molecular Biology
University of Michigan
Postdoctoral Fellowship in Rheumatology
University of Michigan
Postdoctoral Fellowship in Hematology
University of Washington
Tulane University, Honors in Biology
National Research Service Award, NIH
Keystone Symposium Scholarship, ‘From Stem Cells to Therapy’, E3
(206) 221-4579
Mailing Address: 

University of Washington

Health Sciences Building, K-228C

Box 357720

Seattle, WA 98195

Research & Clinical Interests
Research Interests: 

My research program focuses on understanding pathophysiology of facioscapulohumeral dystrophy (FSHD) and developing therapeutic tools to modulate expression of genes responsible for the most common adult muscular dystrophies, FSHD and myotonic dystrophy (DM).  The approach we are developing for therapy of these dominant genetic diseases guides the endogenous RNA interference (RNAi) pathway to turn down disease-causing gene expression in a sequence specific manner.  RNAi is triggered by processing of double-stranded antisense RNA for sequence-specific gene silencing through direct base pairing with the target mRNA.  Development of RNAi expression cassettes in muscle is a main focus of the laboratory.  Both ubiquitous and tissue-specific promoters are incorporated into muscle tropic adeno-associated virus vectors (AAV) to drive RNA hairpin expression for targeted RNAi throughout the musculature.  The RNAi expression vectors are tested both in cell cultures and in pre-clinical disease models, with the ultimate goal of preventing the effects of unwanted gene expression leading to human disease.


Our challenge is to couple timely intervention with a safe and effective therapy. As we learn more about FSHD and DM and the details of the RNAi pathway, we are better able to show feasibility of this approach in complex living organisms.  To investigate potential disease intervention pathways for FSHD therapy development, a mouse model was generated from expression of the human FSHD disease gene DUX4 in muscle.  The DUX4 promoter and gene are expressed following delivery AAV delivery to normal mouse muscle.  The AAV-DUX4 model manifests many FSHD disease features and mechanisms underlying disease pathophysiology are under investigation.  Mitigating disease in mouse models of both FSHD and DM demonstrated proof-of-principle for the therapeutic RNAi approach.  Studies are underway to refine this and other gene-expression strategies to attain the ultimate goal of producing a therapy for dominant genetic disease of muscle and, in general, for treating disease by modulation of gene expression.


Bengtsson NE, Hall JK, Odom GL, Phelps MP, Andrus CR, Hawkins RD, Hauschka SD, Chamberlain JR and Chamberlain JS:  Enhanced muscle-specific CRISPR/Cas9 editing of the dystrophin gene ameliorates pathophysiology in a mouse model of DMD.  Nat Commun 2017. doi:10.1038/ncomms14454.

Bisset, DR, Stepniak-Konieczna, EA, Zavaljevski, M, Wei, J, Carter, GT, Weiss, MD, and Chamberlain, JR. Therapeutic impact of systemic AAV-mediated RNA interference in a mouse model of myotonic dystrophy. Hu Mol Gen 2015; 24:4971-4983. PMID: 26082468

Bortolanza, SB, Nonis, A, Sanvito, F, Maciotta, S, Sitia, G, Wei, J, Torrente, I, Di Serio, C, *Chamberlain, JR, and *Gabellini, D. AAV6-mediated systemic shRNA delivery reverses disease in a mouse model of facioscapulohumeral muscular dystrophy. Mol Therapy 2011; 19(11):2055-2064. doi:10.1038/mt.2011.153. PMID: 21829175 *Chamberlain and Gabellini co-corresponding authors.

Chamberlain, JR, and Chamberlain, JS. Muscling in: Gene therapies for muscular dystrophy target RNA. Nat Medicine 2009; 16:170-171. PMID: 20134472

Chamberlain JR, Deyle, DR, Schwarze U, Wang P, Hirata RK, Li Y, Byers PH, Russell DW. Gene targeting of mutant COL1A2 allelles in mesenchymal stem cells from individuals with osteogenesis imperfecta. Mol Ther 2008; 16:187-193. PMID: 17955022

Banks, GB, Combs, AC, Chamberlain, JR, and Chamberlain, JS. Molecular and cellular adaptations to chronic myotendinous strain injury in mdx mice expressing a truncated dystrophin. Hum Mol Genet 2008; 17:3975-3986. PMID: 18799475

Chamberlain JR, Schwarze U, Wang PR, Hirata RK, Hankenson KD, Pace JM, Underwood RA, Song KM, Sussman M, Byers PH, Russell DW. Gene targeting in stem cells from individuals with osteogenesis imperfecta. Science 2004; 303:1198-1201. PMID: 14976317

Hirata R, Chamberlain J, Dong R, and Russell DW. Targeted transgene insertion into human chromosomes by adeno-associated virus vectors. Nat Biotechnol 2002; 20:735-738. PMID: 12089561

Chamberlain JR, Lee Y, Lane WS, and Engelke DR. Purification of the nuclear RNase P holoenzyme complex reveals extensive subunit overlap with RNase MRP. Genes Dev 1998; 12:1678-1690. PMID: 9620854

Chamberlain JR, Pagán-Ramos E, Kindelberger DK and Engelke DR. An RNase P RNA subunit mutation affects ribosomal RNA processing. Nucleic Acids Res 1996; 24:3158-3166. PMID: 8774895

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. PMID: 1573747

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; 16:11141-11156. PMID: 3205741

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; 239:1416-1418. PMID: 3347839