Andrei Maiseyeu
Case Western Reserve University, OH·Pharmacology
Diseases of the heart muscle, called cardiomyopathies, cause disability and early death, and most forms have no treatment that slows their course. Gene therapy could in principle correct the faulty genes behind some of them, but the viral carriers used to deliver genes end up mostly in the liver instead of the heart.
- Fields
Pharmacology
Biomedical Engineering
Medicine & Clinical Research
- Topics
cardiomyopathy
heart failure
gene therapy
- Grants
- 3 known grants, through May 2028
What they work on
- Define which nanoparticle design parameters govern where adeno-associated virus (AAV) gene therapy vectors travel in the body and how much is taken up by heart muscle.
- Test whether "bait-and-switch" nanoparticles, which block AAV clearance by liver Kupffer cells and transiently alter cardiac sugar coatings, reverse disease features in a genetic mouse model of hypertrophic cardiomyopathy.
- Quantify cardiac gene transfer efficiency of the nanoparticle-AAV approach in a pig model to gauge translational potential.
- Test the risk-benefit, generality and reproducibility of heart-redirected targeting using an engineered polymeric adjuvant co-delivered with AAVs, nanoparticles, oligonucleotides or antibodies, and elucidate its mechanism in human-relevant cell models.
- Test long-term efficacy of heart-redirected delivery of an AAV carrying the frataxin (FXN) gene in a mouse model of Friedreich's ataxia, where cardiomyopathy is the main cause of death.
- Characterize how chronic exposure to fine particulate matter (PM2.5) changes inflammation-resolution pathways and how far these overlap with the effects of dietary manipulation.
- Identify intervention strategies, including diet switching and a pharmacological mimic of exposure cessation, that promote resolution of air pollution-induced inflammation.
More about the research
Two of these projects develop particles and polymers that redirect therapies to heart muscle. A third project studies how fine-particle air pollution drives heart and metabolic disease, and how the inflammation it causes can be resolved.
Why it matters
Cardiomyopathies are a leading cause of disability and premature death with few disease-modifying options. Redirecting gene therapy to the heart could lower doses, reduce immune and liver toxicity, and make treatments feasible for patients with hypertrophic cardiomyopathy or Friedreich's ataxia, where heart failure drives mortality. The air pollution work could point to dietary or drug strategies that blunt the cardiovascular and metabolic harm of PM2.5 exposure.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Ronald G Crystal
Weill Medical College of Cornell University, NY·Medicine & Clinical Research
Secure Investigational New Drug approval and manufacture clinical-grade AAV8hAAT(AVL), a virus vector carrying an oxidation-resistant form of alpha 1-antitrypsin, the protein that blocks lung-digesting enzymes.
Ju Chen
University of California-San Diego, CA·Physiology
Test whether mini-ALPK3, a shortened version of the ALPK3 kinase delivered by the muscle-targeting MyoAAV virus on the first day of life, prevents cardiomyopathy and early death in Alpk3 knockout mice.
Ryan Stowers
University of California-Santa Barbara, CA·Biomedical Engineering
Determine whether cardiomyopathy-driven remodeling of the extracellular matrix alters myocardial viscoelasticity, by mechanically testing human DCM and HCM heart tissue and pig disease-model tissue.
The school
Case Western Reserve University: 34 labs on PI Pages, $643M a year on research, 213 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.