SIF176D Prominence-to-Preeminence (P2PE) STEM Targeted Initiatives Fund

Immunology and Informatics for Precision ImmunoMedicine (iPRIME) in Cardiovascular Disease

Project Manager: Coleen McNamara

Approved: November 2021

Project Dates: 3/01/2022 – 2/28/2027

Total Funding: $5,500,000

Executive Summary

In collaboration with the Schools of Medicine, Engineering and Applied Science, Nursing, and Data Science, the goal of implement Precision ImmunoMedicine (iPRIME) is to designate UVA as the premier location for targeting the immune-system for research, diagnosis, prognosis and treatment of cardiovascular disease (CVD) using cutting edge technology, advanced clinical imaging, and innovative, sophisticated artificial intelligence. The team has collected substantial data from patient subjects and has the systems in place to recruit and obtain high dimensional immune system and imaging data and clinical outcomes on another 1000 CVD subjects over the next five years. The team has successfully used bioinformatics and machine learning in cohorts to develop algorithms to assist clinical decision making as a proof of concept. Melding all of these data and topics together will lead to fully realizing the potential preeminence for UVA in precision immunomedicine in CVD.

Progress:

Cardiovascular diseases (CVD) are the leading cause of death globally, costing an estimated 17.9 million lives each year. CVD is caused mainly by atherosclerosis, a thickening or hardening of the arteries caused by a buildup of plaque in the inner lining. Importantly, inflammation is recognized as a key component of the disease. Atherosclerotic lesions contain various immune cells coupled with cholesterol infiltrates from the blood. While therapeutics targeting the immune response are currently the fastest growing class of drugs, the challenge of elucidating biomarkers and defining how best to deliver targeted patient-specific approaches remains. Our goal is to reduce barriers for investigators to perform cutting-edge research on cardiovascular diseases, and designate UVA as the premier location for targeting the immune-system for research, diagnosis, prognosis, and treatment of cardiovascular diseases.

Since our inception and funding through the Prominence-to-Preeminence (P2PE) STEM Targeted Initiative Fund in 2021, we have focused on our mission of advancing Precision ImmunoMedicine by linking experts in Immunology, Imaging, and Informatics (iPRIME). Our efforts in year one and year two have focused on building a strong foundation to ensure our collaborative team, our renovated space, and our scientific aims would allow programmatic success. Milestones for year one include: (1) Recruitment and retention of a core iPRIME team focused on supporting Human Translational Immunology Research; (2) Development and implementation of a workflow for human biospecimen collection and novel immunoassay analysis; (3) Creation of informatic pipelines for single-cell data analysis and artificial intelligence approaches; (4) Recruitment of an Immunomodulatory Clinical Trial Physician-Scientist; and (5) Engagement with cross-disciplinary students and faculty. To date, we have enrolled over 1100+ patients undergoing cardiac imaging at UVA. These patient cohorts contain clinical imaging data, high-quality cryopreserved immune cells, DNA, plasma, and relevant clinical data. Milestones for year two include: (1) Catalyzing interdisciplinary research through faculty seed funding and student fellowships; (2) Building a Precision ImmunoMedicine Data Commons in iTHRIV; (3) Increasing knowledge of cardiovascular disease pathogenesis to maximize efficacy and minimize toxicity of treatments; and (4) Inclusion of CVD patients in immunomodulatory clinical trials at UVA.

As we progress into year three, we remain focused on continued discovery of novel biomarkers of disease, using artificial intelligence to predict disease outcome, and determining personalized cardiovascular disease therapy response and risk.