Collaborative Patient-Centered Research (CPCR)
Driving collaboration across research centers and leveraging resources to broadly advance science are centerpieces of the Vascular Cures research portfolio. The Collaborative Patient-Centered Research (CPCR) grants fund multi-institutional high-impact projects that create shareable research assets and generate milestones within two years.
2020 CPCR Grant Awards
The 2020 CPCR grants have been awarded to two teams of established clinician-scientists at four leading academic medical centers, supported by a collaborative research laboratory and computational resources at UCSF. The program’s goal is to identify biomarkers of poor response to procedures, to improve the patient prognosis and identify new targets for future drugs.
Peripheral artery disease (PAD) and abdominal aortic aneurysms (AAA) cause significant disability and mortality. Improved technologies have enabled less-invasive treatments, but their long-term effectiveness is limited and new interventions are often necessary. Multiple studies suggest certain molecules in our blood influence vascular repair and may serve as biomarkers to predict a positive, or negative, outcome.
The impact on patient lives would be enormous if researchers could identify the biological factors (biomarkers) that predict the success or failure of these procedures for individual patients. The proposed projects would enable major progress toward the ultimate development of validated tests to predict this response.
Project 1: Identification of Biomarkers of Aortic Aneurysm Growth and Healing Following EVAR
Investigators: Edith Tzeng MD, UPMC (PI), John Curci MD, Vanderbilt University
Currently, AAA are treated surgically with endovascular aneurysm repair (EVAR) but approximately 25% of patients still have persistent AAA growth and remain at risk for rupture – fatal 90% of the time. The AAA project will enroll 80 patients over two years, and also collect blood samples and imaging data.
Project 2: Exosomes as Key Signaling Mediators of Lower Extremity Vein-Graft Outcomes
Investigators: Michael Conte MD, UCSF, Scott Berceli MD, PhD, University of Florida
Dr. Conte and Dr. Bercelli did previous CRM work that provided key insights in terms of the inflammatory response. In this study blood samples will be collected more frequently and at earlier time points after surgery, along with high-resolution ultrasound imaging. 60 patients undergoing leg bypass surgery will be enrolled.
Collaborative Research Labs: Adam Oskowitz, MD, PhD, UCSF and Robert Raffai, PhD, UCSF & Department of Veterans Affairs
For both projects, a panel of biomarkers will be measured and correlated with adverse outcomes post-surgery. Circulating exosomes (agents of intercellular communication, e.g. immune response) will also be isolated, studied for their cell signaling properties, and profiled using cutting-edge RNA sequencing technology.
2016 CPCR Grant Awards
The 2016 grants were awarded to teams led by Dr. Karen Ho at Northwestern University and Dr. Larry Kraiss at the University of Utah School of Medicine
Project 1: Gut Microbe-Dependent Metabolites as Modulators and Biomarkers of Atherosclerosis
Investigators: Karen Ho, MD, Northwestern University (PI), Eugene Chang, MD, Mary McDermott, MD, C. Keith Ozaki, MD
Dr. Karen Ho, with collaborators at the University of Chicago and Harvard, is studying the mechanism by which some of the trillions of microbes that live in our gut influence the development of severe atherosclerosis (narrowing of the arteries), including peripheral arterial disease. The study has already completed its first milestone, a pilot study to expand our understanding of the specific molecules linked to severe atherosclerosis. The results, titled “Microbiome-modulated Metabolites and Advanced Atherosclerosis”, was published in the Journal of Vascular Surgery in 2018. Learn more about Dr. Ho’s work in the recent video Predicting PAD: Your Gut Microbiome.
Project 2: Implementing Pre-operative Frailty Assessment in the Vascular Surgery Clinic
Investigators: Larry Kraiss, MD, University of Utah (PI), Benjamin S. Brooke, MD PhD, Shipra Arya, MD, Philip P. Goodney, MD, Matthew Mel, MD, George K. Lee, MD, Jason Johanning, MD
Dr. Larry Kraiss, with collaborators at Emory, Dartmouth, Stanford, and Nebraska is developing a tool to predict a patient’s ability to maintain independent living following surgery. The goal is to enable patients and clinicians to make fully informed decisions about whether or not to have surgery. Since funding, five sites have initiated the clinical trial approval process and 46 patients have been enrolled to date. Dr. Kraiss’ work is shown on our YouTube channel video Using Frailty to Predict Surgical Outcomes.
2012 PREDICT-PVI Study
Understanding Peripheral Restenosis: Genomic and Proteomic Determinants of Vascular Intervention (PREDICT-PVI) Investigators: Michael Conte MD, UCSF, Scott Berceli, MD PhD, University of Florida
This project was initiated to gather tissue and data to create a national vascular biobank and improve the success rate of procedures to open blocked arteries in the leg for patients suffering from peripheral artery disease (PAD). The inflammatory response and its resolution are critical to the healing of blood vessels. Excessive scarring of vessels is a common cause of failure of angioplasty, stents, bypass grafts and the arteriovenous fistulas that allow for dialysis. Recent work has identified critical pathways of the resolution, including those governed by bioactive lipids derived from omega-3 fatty acids (e.g. fish oils). The goal of the first PREDICT-PVI study is to define a set of protein and lipid inflammatory mediators that exhibit a patterned response after surgery, identifying them as candidate biomarkers or treatment targets to improve vascular healing.