Joseph Chen

Hyperglycemia Acutely Increases Cytosolic Reactive Oxygen Species via <i>O</i> -linked GlcNAcylation and CaMKII Activation in Mouse Ventricular Myocytes

Circulation Research · 2020-03-18 · 145 citations

Rationale: Diabetes mellitus is a complex, multisystem disease, affecting large populations worldwide. Chronic CaMKII (Ca 2+ /calmodulin-dependent kinase II) activation may occur in diabetes mellitus and be arrhythmogenic. Diabetic hyperglycemia was shown to activate CaMKII by (1) O -linked attachment of N-acetylglucosamine ( O -GlcNAc) at S280 leading to arrhythmia and (2) a reactive oxygen species (ROS)–mediated oxidation of CaMKII that can increase postinfarction mortality. Objective: To test…

mTORC2 controls the activity of PKC and Akt by phosphorylating a conserved TOR interaction motif

Science Signaling · 2021-04-13 · 111 citations

-F-pT), which controls the phosphorylation of the hydrophobic motif of PKC and Akt and the activity of these kinases. The TIM is invariant in mTORC2-dependent AGC kinases, is evolutionarily conserved, and coevolved with mTORC2 components. Mutation of this motif in Akt1 and PKCβII abolished cellular kinase activity by impairing activation loop and hydrophobic motif phosphorylation. mTORC2 directly phosphorylated the PKC TIM in vitro, and this phosphorylation event was detected in mouse brain. Ove…

Parallel Lineage-Tracing Studies Establish Fibroblasts as the Prevailing In Vivo Adipocyte Progenitor

Cell Reports · 2020 · 89 citations

Despite decades of studies suggesting that the in vivo adipocyte progenitor resides within the vascular niche, the exact nature of this progenitor remains controversial because distinct studies have attributed adipogenic properties to multiple vascular cell types. Using Cre recombinases labeling distinct vascular lineages, we conduct parallel lineage tracing experiments to assess their degree of contribution to de novo adipogenesis. Although we detect occasional adipocytes that were lineage trac…

Transcriptional readthrough at <i>Atf4</i> locus suppresses <i>Rps19bp1</i> and impairs heart development

Cardiovascular Research · 2025-11-14 · 2 citations

AIMS: Activating transcription factor 4 (ATF4) functions as a transcriptional regulator in various cell types and tissues under both physiological and pathological conditions. While previous studies have linked ATF4 activation with promoting cardiomyocyte (CM) death in dilated cardiomyopathy (DCM), atrial fibrillation, and heart failure, its role in developing CMs remains unexplored. METHODS AND RESULTS: We generated multiple distinct CM-specific (Atf4cKO(e2/3/pA) and Atf4cKO(e2)) and global Atf…

A Novel miniALPK3 Gene Therapy for ALPK3-Associated Cardiomyopathy

Circulation · 2025-11-17 · 1 citations