Decoding the Role of Mechanosensitive Signaling in DIPG/DMG

Diffuse intrinsic pontine glioma (DIPG) is a rare and devastating brain cancer that primarily affects children. It grows in the pons, a critical area in the brainstem that controls breathing, movement, and other vital functions. Because of its location, DIPG cannot be surgically removed, and current treatments are largely ineffective. Most children diagnosed with DIPG survive less than one year, highlighting the urgent need for new therapeutic approaches.

Recent discoveries suggest that DIPG growth is driven not only by genetic changes within tumor cells, but also by signals from the surrounding area. The goal of this research is to understand how physical and neural signals in the pons drive DIPG progression and to use this knowledge to develop new therapeutic strategies. First, we will determine how the physical stiffness of brain tissue influences DIPG growth and invasion. By recreating brain-like environments with different mechanical properties, we will test how tumor cells respond to changes in tissue stiffness and identify the signaling pathways involved. Second, we will investigate how DIPG cells use mechanical sensing to interact with the surrounding neurons. We will test whether the ability of tumor cells to connect with neural circuits and respond to neuronal activity depends on specific mechanosensitive proteins. Understanding this process will reveal how brain activity directly fuels tumor growth. Third, we will develop therapeutic peptides designed to block mechanical signaling. Using cutting-edge protein engineering approaches, we will optimize the peptides for stability and effectiveness, and test whether they can suppress tumor growth in preclinical models of DIPG.

By focusing on how DIPG tumors exploit the physical and neural features of the brain, this work aims to establish a new framework for understanding brain cancer and lay the foundation for therapies that disrupt tumor-environment interactions rather than targeting tumor cells alone.