Frontiers in Signaling and Post-Translational Modification (PTM) Research 2026

This is a Research Topic initiated by NAVBO, the North American Vascular Biology Organization. Our goal is to identify the next frontiers in atherosclerosis research and to drive the development of innovative clinical approaches.

Over the past decades, the field of signaling and PTMs has evolved dramatically. A wide array of signaling pathways and PTM mechanisms have been uncovered, revealing the intricate complexity of molecular interactions and their roles in cellular function and disease. Kinases and phosphorylation events, for example, have revolutionized cancer therapy, leading to the development of targeted drugs that are now widely used in oncology. However, the translation of these advances into cardiovascular medicine has been limited. This discrepancy stems from several challenges: cardiovascular diseases tend to be chronic, making long-term application of kinase inhibitors more prone to resistance—an issue also observed in cancer treatment. Moreover, the development of highly specific inhibitors or activators remains difficult due to the overlapping nature of signaling pathways and PTMs. Similar challenges apply to other PTMs such as PARylation, SUMOylation, and Neddylation, which often affect multiple substrates and downstream processes, complicating therapeutic targeting.

Given these complexities, our goal is to foster bold, innovative, and even provocative ideas that challenge existing paradigms and open new directions for the field. We understand that such visionary concepts—especially those that break from traditional frameworks—may face challenges in gaining acceptance elsewhere. Therefore, this Research Topic is designed to provide a dedicated platform for transformative thinking, welcoming submissions that push boundaries and offer fresh perspectives on signaling and post-translational modification in health and disease.

To overcome these limitations, the integration of AI-based approaches offers a promising path forward. Machine learning and computational modeling can help decode complex signaling networks, predict PTM sites, and simulate dynamic interactions across cellular systems. These tools enable researchers to better understand feedback mechanisms, chronic versus acute signaling phases, and the convergence of protein, RNA, and metabolic regulation. By embracing interdisciplinary strategies, we aim to foster transformative ideas that challenge existing paradigms and open new directions for research and clinical innovation.

We invite original research articles, reviews, and perspectives on topics including, but not limited to:

• Discovery of novel PTMs and their substrates

• Functional consequences of signaling interactions

• Emerging models of signaling transduction, including feedback loop dynamics in both acute and chronic phases of cardiovascular disease

• Roles of signaling and PTMs in cellular senescence and aging

• Integration of protein, mRNA, and metabolic networks through signaling and PTMs

• Epigenetic regulation, including DNA methylation and histone modifications, and their modulation by signaling and PTMs

• Integrated signaling and post-translational modification networks regulating endothelial and mitochondrial function in vascular health and disease.

• Comparative analysis of acute vs. chronic signaling phases and their implications in cardiovascular pathology

We look forward to your contributions and to collectively advancing the next chapter in signaling and PTM research.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Review
• Study Protocol
• Systematic Review

Keywords: Signaling Pathways, Post-Translational Modifications, Cardiovascular Disease, Kinase Inhibitors, Artificial Intelligence, Machine Learning, Protein Networks, Epigenetic Regulation, Cellular Senescence, Computational Modeling

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.