CAREER: Lipid-based Nanotechnologies to Investigate the Role of Hypoxia and Inflammation on Disease Progression through Pathophysiological Mimicry

About This Grant

Hypoxia and inflammation are hallmark characteristics that drive progression of a myriad of diseases including cancer, chronic diseases, diseases of pregnancy, and more. However, there is a lack of tools available to study the biological mechanisms underlying how these environmental conditions drive disease onset and progression. The goal of this project is to develop lipid nanoparticles (LNPs) as tools to study how oxygen levels and inflammation influence pregnancy health. These advances will uncover potential therapeutic strategies to treat diseases of pregnancy and other diseases characterized by low oxygen or excessive inflammation. This research is integrated with educational activities focused on providing early research exposure to increase scientific participation. Specifically, it will provide pathways for undergraduate students at a local community college to work on translational research, integrate the research objectives into undergraduate and graduate coursework, provide summer research opportunities for students, and prepare modules for K-12 outreach. This project aims to develop and use LNPs as tools to study the role of oxygen- or immune-related pathways during healthy and pathologic pregnancy. LNPs have been predominately used for therapeutic nucleic acid delivery to treat and vaccinate against diseases. This work aims to shift the paradigm of using LNPs as therapeutics to also being used as tools to study biological processes underlying healthy and pathologic tissues. Both oxygen levels and immune activity are intricately controlled throughout pregnancy to support healthy placenta development and function, and their dysregulation can lead to pregnancy-related pathologies throughout gestation. However, there is a severe lack of living models, and therefore a lack of treatment options, available to study the pathophysiology of these conditions. To fill this gap, this project will design LNPs that preferentially accumulate in the diseased placenta and use these LNPs to investigate key biological questions relating inflammation and hypoxia to placenta health. This work integrates both non-living and living components to form a fundamental understanding of the molecular drivers of pathophysiology of pregnancy. The successful completion of this work will uncover potential therapeutic avenues to treat diseases of pregnancy, which currently have very limited treatment options. Further, it establishes LNPs as tools for studying pathophysiology across numerous diseases driven by hypoxia or inflammation, revolutionizing the way diseases are studied and leading to the development of new therapeutic approaches. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.