Research in the Shaw Lab centers on the cell biology of heart arrhythmias and heart failure: how cardiac ion channels are made, how the cytoskeleton delivers them to exactly where they need to function in the heart muscle cell, and how those processes break down in disease — work that spans from RNA translation to clinical studies of patients with heart failure.
Research Areas
Targeted Delivery
The Shaw Laboratory defined the paradigm of Targeted Delivery: the cytoskeleton delivers membrane proteins directly to their functional membrane subdomain. The lab studies Connexin43 gap junction trafficking to the cardiomyocyte intercalated disc and L-type calcium channel (CaV1.2) trafficking to cardiomyocyte T-tubules. In the failing heart, oxidative stress disrupts this delivery machinery, reducing the number of channels that reach their destination. The structural protein GJA1-20k helps organize the actin and microtubule ‘highways’ that carry channels to the membrane.
Representative publication: Xiao S, et al. J Clin Invest. 2020.
GJA1-20k and Alternative Translation
The Cx43 gene (GJA1) is alternatively translated — in an mTOR-dependent process — to produce up to seven proteins from a single mRNA. The most abundant truncated isoform, GJA1-20k, is essential for forward trafficking of full-length Connexin43 to the intercalated disc and protects it from degradation.
GJA1-20k and Mitochondrial Function
Beyond trafficking, GJA1-20k organizes the actin cytoskeleton to regulate mitochondrial organization, transport, and function, including mitochondrial protection and ischemic preconditioning.
Representative publication: Baum R, et al. J Cell Biol. 2025.
Biomarker and Therapeutic Development
Cardiac BIN1 (cBIN1) folds T-tubule membrane and organizes the calcium-handling machinery of the heart muscle cell. Because cBIN1 is released into the blood, it forms the basis of the cBIN1 Score, a blood-based biomarker of cardiac muscle health being developed with Sarcotein Diagnostics. The lab is also developing cBIN1 gene therapy as a treatment for heart failure.
Representative publication: Hong T, et al. Nat Med. 2014.