Gabriela Chiosis

Human diseases have a multifaceted origin involving internal and external factors that disrupt cells, tissues, organs, and organisms. These disruptive agents, referred to as stressors, can be acute or chronic, and their effects on biological systems are complex. The response to stressors, whether it leads to adaptation or maladaptation, is influenced by factors such as the duration, intensity, predictability, and controllability of the stressors, as well as genetic and environmental factors. To develop realistic drugs and therapies that target the intricate and biologically relevant networks underlying diseases, a shift in perspective, away from the unitary protein approach, is required. Particularly, protein-protein interaction (PPI) networks play a vital role in this context as they encode and execute the flux of information linking stressors to phenotype at the cellular level. As cells do not function in isolation, the effect of PPI networks reverberates and extends beyond individual cells, and into tissue and whole organism levels. The disease PPI network, which represents the alterations in cellular PPIs caused by stressors and their impact on the system, becomes a target for therapeutic interventions. From a network standpoint, proteins are not treated as isolated entities but rather as interconnected elements whose significance is defined by the number and structure of their connections within the network.  

To effectively combat diseases, it is thus crucial to comprehend and leverage the unique biological networks that arise from the interplay between genetic and environmental stressors. This necessitates moving away from a reductionist approach focused solely on individual proteins and instead targeting the specific dysfunctions within context-specific PPI networks. The primary objective of the Chiosis lab is to gain insights into such disease-causing dysfunctions within PPI networks, ultimately identifying, targeting, and manipulating these dysfunctions to achieve therapeutic efficacy and enable precision medicine. By understanding how stressors disrupt PPI networks and the resulting system perturbations, we aim to uncover potential targets for therapeutic intervention. This knowledge can lead to more effective and tailored treatments for complex diseases such as cancers and neurodegenerative disorders.