About

Joel Chamberlain is a professor in the Department of Neurology at the University of Washington. His research focuses on neuroinflammation, microglia, and ischemic stroke, with particular interest in the role of interferon signaling in microglia and its neuroprotective effects. He is involved in various collaborative projects exploring the cellular mechanisms underlying stroke and neuroinflammatory responses, utilizing transgenic mouse models and neurobehavioral testing paradigms. Dr. Chamberlain has contributed to the understanding of how microglia and immune signaling pathways influence neuroprotection and recovery following ischemic injury. His work is supported by multiple awards, including the NIH/NINDS NRSA Post-Doctoral Research Fellowship, and he has mentored numerous students and research assistants in his laboratory. As a faculty member, he is dedicated to advancing translational research in neurology, particularly in the areas of stroke and neuroinflammation, and collaborates with other leading scientists at the University of Washington and beyond.

Research topics

• Biology
• Genetics
• Internal medicine
• Medicine
• Pathology
• Endocrinology
• Bioinformatics
• Cardiology
• Molecular biology
• Cell biology

Selected publications

• Assessment of systemic AAV-microdystrophin gene therapy in the GRMD model of Duchenne muscular dystrophy

  Science Translational Medicine · 2023 · 67 citations

  • Medicine
  • Internal medicine
  • Pathology

  = 3 each], treated intravenously at 3 months of age with a canine codon-optimized microdystrophin construct, rAAV9-CK8e-c-μDys5, and followed for 90 days after dosing. All dogs received prednisone (1 milligram/kilogram) for a total of 5 weeks from day -7 through day 28. We observed dose-dependent increases in tissue vector genome copy numbers; μDys5 protein in multiple appendicular muscles, the diaphragm, and heart; limb and respiratory muscle functional improvement; and reduction of histopathologic lesions. As expected, given that a truncated dystrophin protein was generated, phenotypic test results and histopathologic lesions did not fully normalize. All administrations were well tolerated, and adverse events were not seen. These data suggest that systemically administered AAV-microdystrophin may be dosed safely and could provide therapeutic benefit for patients with DMD.

  DOI

• Micro-dystrophin gene therapy prevents heart failure in an improved Duchenne muscular dystrophy cardiomyopathy mouse model

  JCI Insight · 2021 · 29 citations

  • Medicine
  • Cardiology
  • Internal medicine

  Gene replacement for Duchenne muscular dystrophy (DMD) with micro-dystrophins has entered clinical trials, but efficacy in preventing heart failure is unknown. Although most patients with DMD die from heart failure, cardiomyopathy is undetectable until the teens, so efficacy from trials in young boys will be unknown for a decade. Available DMD animal models were sufficient to demonstrate micro-dystrophin efficacy on earlier onset skeletal muscle pathology underlying loss of ambulation and respiratory insufficiency in patients. However, no mouse models progressed into heart failure, and dog models showed highly variable progression insufficient to evaluate efficacy of micro-dystrophin or other therapies on DMD heart failure. To overcome this barrier, we have generated the first DMD mouse model to our knowledge that reproducibly progresses into heart failure. This model shows cardiac inflammation and fibrosis occur prior to reduced function. Fibrosis does not continue to accumulate, but inflammation persists after function declines. We used this model to test micro-dystrophin gene therapy efficacy on heart failure prevention for the first time. Micro-dystrophin prevented declines in cardiac function and prohibited onset of inflammation and fibrosis. This model will allow identification of committed pathogenic steps to heart failure and testing of genetic and nongenetic therapies to optimize cardiac care for patients with DMD.

  DOI

• Dystrophin Gene-Editing Stability Is Dependent on Dystrophin Levels in Skeletal but Not Cardiac Muscles

  Molecular Therapy · 2020 · 24 citations

  Senior authorCorresponding
  • Biology
  • Cell biology
  • Genetics
  DOI

Recent grants

• NIH Grant P01NS046788

  NIH · $25.9M · 2014

• Therapeutic potential for AAV/micro-dystrophin transfer to cardiopulmonary tissue

  NIH · $2.0M · 2015–2019

• NIH Grant U54HD047175

  NIH · $8.1M · 2009

• Overcoming limitations for AAV gene therapy

  NIH · $25.1M · 2014–2028

• Assembly of the Dystrophin-Glycoprotein Complex

  NIH · $9.8M · 1997–2022

Frequent coauthors

• Paul Gregorevic

  75 shared

• Louis M. Kunkel

  72 shared

• K. Olek

  Max Perutz Labs

  64 shared

• K.-M Seil

  Heidelberg University

  64 shared

• C Hasslacher

  Heidelberg University

  64 shared

• D. Ratge

  Robert Bosch Hospital

  64 shared

• M Bachern

  64 shared

• Lansheng Hao

  Ruhr University Bochum

  64 shared

Labs

• Weinstein LaboratoryPI

Similar researchers at University of Washington

• Sarah Jaewon Leeh-151
• Jan Hansenh-130
• Linda Simonsenh-120
• Anna Waldh-119
• Jesse Bloomh-117