Duangnapa Kovanich, Ph.D.

2.Unraveling the Nuclear Role of PDE3A2 in Cardiac Myocyte Hypertrophy: A Proteomics-Driven Discovery Subramaniam G, Schleicher K, Kovanich D, Zerio A, Folkmanaite M, Chao YC, Surdo NC, Koschinski A, Hu J, Scholten A, Heck AJR, Ercu M, Sholokh A, Park KC, Klussmann E, Meraviglia V, Bellin M, Zanivan S, Hester S, Mohammed S, Zaccolo M. Integrated Proteomics Unveils Nuclear PDE3A2 as a Regulator of Cardiac Myocyte Hypertrophy. Circ Res. 2023 Mar 31;132(7):828-848. Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, with cardiac hypertrophy being a key pathological adaptation to chronic stressors. In a groundbreaking study, “Integrated Proteomics Unveils Nuclear PDE3A2 as a Regulator of Cardiac Myocyte Hypertrophy,” we employed state-of-the-art proteomics and Förster Resonance Energy Transfer (FRET) imaging approaches to uncover a previously unrecognized nuclear function of phosphodiesterase 3A2 (PDE3A2) in cardiac myocytes. Through a comprehensive integration of interaction proteomics, phosphoproteomics, and FRET imaging, , the study demonstrated that PDE3A2, classically known for its cytoplasmic role in cyclic nucleotide signaling, localizes to the nucleus where it exerts a direct regulatory influence on transcriptional programs associated with myocyte hypertrophy. Our findings reveal a novel mechanistic paradigm, in which nuclear PDE3A2 modulates hypertrophic gene expression by interacting with key nuclear proteins, ultimately shaping the cellular landscape of pathological remodeling. This study not only expands our fundamental understanding of cardiac signaling but also positions nuclear PDE3A2 as a promising therapeutic target for hypertrophic heart disease. By bridging high-resolution proteomics with cellular functional analyses, our work paves the way for innovative therapeutic strategies aimed at mitigating maladaptive cardiac growth at the nuclear level. 3.A Comprehensive Review of Nanodomain cAMP Signaling in Cardiac Pathophysiology: From Fundamental Insights to Targeted Therapeutic Strategies Zaccolo M, Kovanich D. Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions. Physiol Rev. 2025 Apr 1;105(2):541-591. Cyclic adenosine monophosphate (cAMP) signaling is a cornerstone of cardiac physiology, orchestrating a diverse array of cellular processes that regulate heart function. Over the past decades, research has shifted from viewing cAMP as a diffusible second messenger to recognizing its highly compartmentalized nature, with spatially confined nanodomains that enable precise regulation of cardiac signaling pathways. Understanding these localized cAMP signaling microdomains is critical for developing targeted therapeutic strategies for cardiovascular diseases. In this comprehensive review, we provide an in-depth examination of the evolution of compartmentalized cAMP signaling, tracing its conceptual development from early models of global diffusion to contemporary insights into nanodomain organization. We discuss how cAMP-hydrolyzing enzymes, phosphodiesterases (PDEs), and the A-kinase anchoring protein (AKAP) family work together to finely tune cAMP gradients within cardiac cells. These spatiotemporal regulatory mechanisms ensure the precise control of downstream effectors such as protein kinase A (PKA) and exchange proteins directly activated by cAMP (Epac), which are integral to maintaining normal cardiac function. Furthermore, we explore the pathophysiological implications of disrupted nanodomain cAMP signaling in conditions such as heart failure, arrhythmias, and cardiomyopathies. Dysregulation of localized cAMP compartments can lead to aberrant signaling cascades that contribute to disease progression, making these microdomains promising therapeutic targets. We highlight recent advancements in the development of PDE inhibitors, AKAP disruptors, and compartment-specific modulators, which offer potential for precision medicine approaches in treating cardiac disorders. By synthesizing past and present research, this review serves as a definitive resource on nanodomain cAMP signaling in cardiac pathophysiology. We emphasize the importance of spatially targeted interventions and advocate for the continued exploration of compartmentalized signaling mechanisms as a means to develop more effective and selective cardiac therapies.