PROJECT SUMMARY
Atherosclerotic cardiovascular diseases (ASCVDs) are the leading cause of death in the United States and
worldwide. Atherosclerosis of the arteries underlies these conditions and is characterized by chronic
inflammation and inappropriate proliferation of disease contributing cells. Current medications available for the
treatment of atherosclerosis merely target risk factors, not the disease-causing cells themselves. Additionally,
invasive procedures such as percutaneous coronary intervention (PCI) treat arterial stenosis but can have
adverse effects such as thrombosis. Therefore, despite progress in the field, site-specific and cell-selective
therapies that target the cells that form atherosclerotic plaques while sparing the vascular endothelium are not
available. Thus, the main objective of this research proposal is to test the feasibility of a novel messenger RNA
(mRNA) therapeutic that is site-specific in targeting regions of atherosclerotic plaques only, while specifically
targeting disease causing cells, reducing inflammation, and sparing the vascular endothelium. This research is
highly significant to public health as ASCVDs represent a major public health issue and place an enormous
burden on our Nation. I hypothesize that a combination of microRNA (miRNA) switch and small interfering RNA
(siRNA) technology into a single mRNA construct will allow for a first of its kind RNA therapeutic strategy to
cause atherosclerotic plaque regression and resolution. In order to test the efficacy of this new therapeutic, I
will employ a series of rigorous experiments using in vitro, in vivo, and ex vivo models. Importantly, my ex vivo
model uses freshly isolated coronary arteries from human hearts, giving more clinical relevance to my work
and allowing me to test my therapeutic on human arteries burdened with atherosclerotic plaques. We aim to
make a positive impact on the field by not only designing a novel mRNA therapeutic to treat atherosclerosis,
but also, by providing evidence for the effectiveness of this unique therapeutic strategy that can be modified in
order to treat other diseases. I will work towards this goal under the mentorship of my sponsor, Dr. Hana
Totary-Jain, an expert in the field of CVD as well as RNA therapeutic research, at the supportive research
environment of USF Health’s Morsani College of Medicine. My mentor, committee, additional advisors, and
department will provide me with all the necessary training and resources needed to complete this very
impactful research while also preparing me for my next career stage as a post-doctoral scholar and eventually
a principal investigator.