Flordeliza Villanueva, MD

  • Vice Chair for Pre-Clinical Research
  • Director of Non-Invasive Cardiovascular Imaging
  • Director of the Center for Molecular Imaging & Therapeutics
  • Professor of Medicine and Clinical and Translational Science

    Education & Training

  • Medical School – Boston University – MD
  • Residency – Duke University – Internal Medicine
  • Fellowship – University of Pittsburgh – Cardiac Transplant
  • Fellowship – University of Virginia – Cardiology Clinical and Research
Research Grants

NIH Grants:  R01, T32

Research Summary

She has focused her research on the development of ultrasound contrast agents (microbubbles) for the assessment of coronary microcirculation, ultrasound molecular imaging, and ultrasound-mediated therapeutics. In this regard, Dr. Villanueva is the Director of the Center for Molecular Imaging and Image-Guided Therapeutics at the University of Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute. The Center is a multidisciplinary translational research program that brings together scientists with expertise in physiology, cell biology, acoustics, biomedical engineering, chemistry, physics, imaging, molecular biology, and clinical medicine. Together, this team implements a vision to develop novel imaging methods to identify patient-specific disease markers that can simultaneously function as tailored treatments for cardiovascular disease and beyond.

Dr. Villanueva’s unique and collaborative approach to this research has made Pittsburgh one of the epicenters of ultrasound and ultrasound contrast agent research in the world. Her laboratory was the first to engineer molecularly-targeted microbubbles to bind to biological surfaces, ultimately allowing ultrasonic imaging of disease-specific biomarkers. It also houses the UPMC cam, an ultra-high-speed microscopy imaging system capable of acquiring images at up to 25 million frames per second in either bright-field or fluorescence modes, which is currently the fastest camera in the world. Dr. Villanueva’s team is developing strategies for using ultrasound to non-invasively dissolve blood clots that occur during heart attacks, and has led the development of ultrasound-induced vibration of drug- or gene-carrying microbubbles in the bloodstream to achieve delivery of therapeutics exclusively to the diseased organ – simultaneously using the ultrasound to navigate and instigate the delivery process. This platform has applications to the treatment not only of cardiovascular disease but of cancer and neurologic disease.

Dr. Villanueva has had a career-long commitment to training the next generation of physician-scientists. Over the course of her research, she has mentored numerous trainees spanning high school students to MD and PhD post-doctoral fellows, many of whom have received awards for their research and subsequently moved on to independent faculty positions in Pittsburgh, other parts of the United States, Canada, and Europe.

Representative Publications
  1. Kopechek JA, McTiernan CF, Chen X, Zhu J, Mburu M, Feroze R, Whitehurst DA, Lavery L, Cyriac J, Villanueva FS.   Ultrasound and microbubble-targeted delivery of a microRNA inhibitor to the heart suppresses cardiac hypertrophy and preserves cardiac function.  Theranostics. 2019;9(23):7088-98.
  2. Helfield B, Chen X, Villanueva FS.  Mechanistic insight into sonoporation with ultrasound-stimulated polymer microbubbles.  Ultrasound Med Biol. 2017;43(11):2678-89.
  3. Kooiman K, van Rooij T, Villanueva FS, Qin B, Mastik F, Vos HJ, Klibanov AL, de Jong N Chen X. Focal areas of increased lipid concentration on the coating of microbubbles during short tone-burst ultrasound insonification.  PLoS One. 2017;12(7):e0180747.
  4. Chen X, Wang, J, Pacella JJ, Villanueva FS.  Dynamic behavior of microbubbles during long ultrasound tone-burst excitation: mechanistic insights into ultrasound-microbubble mediated therapeutics using high-speed imaging and cavitation detection.  Ultrasound Med Biol. 2016;42(2):528-38.
  5. Helfield B, Chen X, Watkins S, Villanueva FS. The biophysics of sonoporation through direct correlation of microbubble cavitation and enhanced endothelial cell membrane permeability. Proc Nat Acad Sci. 2016;113(36):9983-8.
  6. Yu FTH, Chen X, Wang J, Qi B, Panday R, Villanueva FS. Low intensity ultrasound mediated liposomal doxorubicin release, cellular uptake kinetics and growth inhibition using polymer microbubbles. Mol Pharmaceutics. 2016;13:55−64.
  7. Pacella, JJ, Brands J, Schnatz F, Chen X, Villanueva FS.  Treatment of microvascular microembolization using microbubbles and long tone burst ultrasound:  an in vivo study.  Ultrasound Med Biol. 2015;41:456-64.
  8. Chen X, Leeman JE, Wang J, Pacella JJ, Villanueva FS.  New insights into mechanisms of sonothrombolysis using ultra-high speed imaging. Ultrasound Med Biol. 2014;40:258-62.
  9. Kopechek J, Carson AR, McTiernan C, Grandis J, Sen M, Hasjim B, Chen X, Villanueva FS.  Ultrasound targeted microbubble destruction-mediated delivery of a transcription factor decoy inhibits STAT3 signaling and tumor growth.  Theranostics. 2015;5(12):1378-87.
  10. Leng X, Wang J, Carson A, Chen X, Fu H, Ottoboni S, Wagner WR, Villanueva FS.  Ultrasound detection of myocardial ischemic memory using an E-selectin targeting peptide amenable to human application. Mol Imaging. 2014 Apr 1;16:1-9.
  11. Chen X, Wang J, Versluis M, de Jong N, Villanueva FS. Ultra-fast bright field and fluorescence imaging of the dynamics of micrometer-sized objects.  Rev Sci Instrum. 2013;84(6):063701-1-13.