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Flordeliza Villanueva, MD

  • Professor of Medicine
  • Vice Chair for Pre-Clinical Research, Department of Medicine
  • Director, Non-Invasive Cardiovascular Imaging
  • Director, Center for Ultrasound Molecular Imaging and Therapeutics

Dr. Villanueva received her BA (summa cum laude, Phi Beta Kappa) and MD (Alpha Omega Alpha Honor Society) from Boston University.  She completed her internal medicine residency at Duke University and cardiology fellowship at the University of Virginia.  In 1992, she joined the faculty at the University of Pittsburgh, where she is currently Professor of Medicine in Cardiology.  She is also the Director of Non-Invasive Cardiovascular Imaging at the UPMC Heart and Vascular Institute, overseeing the clinical imaging programs in Echocardiography, Nuclear Cardiology, and Cardiac Magnetic Resonance.  Academically, she has focused her research on the development of ultrasound contrast agents (microbubbles) for assessment of the microcirculation, ultrasound molecular imaging, and ultrasound-mediated therapeutics.  Dr. Villanueva directs the Center for Ultrasound Molecular Imaging and Therapeutics, a multidisciplinary translational research facility espousing the philosophy that moving technologies from pre-clinical status to the bedside requires strong traditional science, engineering, and entrepreneurship.  Her laboratory was the first to demonstrate that molecularly-targeted microbubbles bind to biological surfaces overexpressing the molecular target, ultimately allowing ultrasonic imaging of disease/function-specific epitopes in vivo.  Her group has led the study of how unique acoustic behaviors of microbubbles can be harnessed to therapeutic effect, such as drug/gene delivery or sonothrombolysis.  

Representative Publications

  1. Villanueva FS, Lu E, Bowry S, Kilic S, Tom E, Wang J, Gretton J, Pacella JJ, Wagner WR. Myocardial ischemic memory imaging with molecular echocardiography. Circulation. 2007;115(3):345-52 (with Editorial Comment). PMID: 17210843.
  2. Carson AR, McTiernan CF, Lavery L, Grata M, Leng X, Wang J, Chen X, Villanueva FS. Ultrasound-targeted microbubble destruction to deliver siRNA cancer therapy. Cancer Res. 2012;72(23):6191-9. PMID: 23010078.
  3. Helfield B, Chen X, Watkins S, Villanueva FS. Biophysical insight into mechanisms of sonoporation. Proc Natl Acad Sci. 2016;113(36):9983-8. PMID: 27551081.
  4. Kopechek JA, Carson AR, McTiernan CF, Chen X, Hasjim B, Lavery L, Sen M, Grandis JR, 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. PMID: 26681983.
  5. 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.

Research Interests

  • Molecular imaging using ultrasound
  • Therapeutic applications of contrast agents/microbubbles
  • Ultrasound-mediated drug and gene delivery

Research Grants

Current research support

1R01 HL146465-01                            Gomez (PI)                                                                 04/01/19-03/31/24

Epigenetic control of smooth muscle cell phenotype during microvascular remodeling Role: Co-Investigator.  Goal: To identify the functional role of epigenetic programming in controlling smooth muscle cells phenotype and participation in microvascular remodeling, which may lead to novel therapeutic approaches to improve lower extremity vascularization in patients with Peripheral Artery Disease.

1R01HL146489                                   Porter (PI)                                                                   09/01/19-08/31/22

Scar Detection and Treatment with Droplet Activation. Role: Co-Investigator. Goal: To use reactivated nanometer-sized droplets of ultrasound contrast agents to detect and quantify early scar formation within the heart and alter the natural course of scar formation.

R01 EB026966                                   Villanueva (PI)                                                            07/01/18-06/30/22

Biological and physical mechanisms of ultrasound/microbubble-mediated therapeutic gene delivery across the endothelial barrier. Role: Principal Investigator. Goal: To develop and explore the underlying mechanisms of a technology employing ultrasound-triggered cavitation of RNA-loaded microbubbles for safe, non-invasive, site-specific, imaged-guided delivery of therapeutic RNA drugs.

Research Council of Norway             Davies (PI)                                                                  07/01/19-02/21/22

Acoustic Cluster Therapy for Improved Treatment of Cancer and Brain Diseases.  Project 1:  Characterization of bubble creation, behavior and biomechanical effects on vessel wall.   Role: Co-Investigator on Project 1.  Goal: To develop a unique approach using phase change nanoemulsion contrast agents for ultrasound mediated therapy of cancer and neurodegenerative disease.

HL129964-01                                      Villanueva (PI)                                                                        2016-2021

National Institutes of Health (NHLBI) T32. Training Program in Imaging Sciences in Translational Cardiovascular Research. Role:  Director.

UG3 HL143192                                   Gladwin (PI)                                                                05/15/19-10/30/20

Sickle Cell Disease and CardiovAscular Risk – Red cell Exchange Trial (SCD-CARRE Trial). Role: Co-Investigator. Goal: To perform a clinical trial to evaluate the effects of automated exchange blood transfusion on patient morbidity and mortality, compared to standard of care among 150 adult high risk SCD patients.

Drexel University                                Wrenn (PI)                                                                  10/01/18-09/30/20

Electrophysiologically-Activated Intravenous Ultrasound Contrast Agent for Imaging the Heart. Role: Co-Investigator.

3R01EB026966-02S1                         Villanueva (PI)                                                           08/20/19-06/30/20

Administrative supplement. Role: Principal Investigator. Adds an Alzheimer’s Disease component to above R01.

3P50CA097190                                  Villanueva (PI Project 2)                                            07/01/15-06/30/20

Specialized Program of Research Excellence (SPORE) – Head and Neck Cancer. Project 2: Optimization of STAT3 Decoy Delivery for Head and Neck Cancer Treatment. Role: Co-Principal Investigator on Project 2. Goal: To clinically translate targeted ultrasound-mediated delivery of STAT3 decoy for metastatic head and neck cancer.

R01HL125777                                     Pacella (PI)                                                                07/01/15-06/30/20

Microbubble-mediated Ultrasonic Therapy for Microvascular Obstruction. Role:  Co-Investigator. Goal: To develop a new treatment for post-ischemic microvascular ‘no reflow’ occurring post stenting for acute myocardial infarction using ultrasound and microbubbles, and to understand mechanisms of action of “sonothrombolysis.”

American Heart Association Go Red for Women Center Grant       Hubel/Catov (PIs)        07/01/15-06/30/20

Women’s Cardiovascular Health and Microvascular Mechanisms: Novel Insights from Pregnancy. Project 2: Glycocalyx Pathways Linking Pregnancy Profile with Microvascular Dysfunction Postpartum. Project 3:  The Placenta as a Window to Maternal Microvascular Disease Risk. Role:  Co-Investigator on Projects 2 and 3.  Goal: To correlate placental abnormalities with coronary flow reserve abnormalities in later life (using myocardial echocardiography to evaluate microvascular flow reserve).

Previous research support (past 3 years)

R01 EB016516                                   Villanueva (PI)                                                             07/01/12-05/31/18

Ultrasound-activated Microbubbles for Targeted siRNA Delivery to Tumor.  Role:  Principal Investigator.  Goal:   To develop approaches to enhance the delivery of siRNA-mediated therapeutics to cancer cell targets based on unique biophysical interactions between siRNA-loaded microbubbles, cells, and ultrasound.

HVI/VMI Innovator Grant                    Villanueva (PI)                                                           05/01/17-04/30/18    

Novel Imaging Strategies of Cerebrovascular Dysfunction in Sickle Cell Disease. Role: Co-Principal Investigator.  Goal: To evaluate intracranial microvascular disease in sickle cell disease using myocardial contrast echocardiography and ultrasound molecular imaging. 

R21EB019582                                     Villanueva (PI)                                                           07/01/16-01/30/18

Targeted Drug Delivery Using Liposomes, Microbubbles, and Ultrasound. Role:  Principal Investigator. Goal:  To optimize doxorubicin-liposome-polymer microbubble constructs for targeted ultrasound delivery to solid tumors.

7POST33420160                                 Helfield (PI)                                                                            2016-2018

American Heart Association Post-Doctoral Fellowship Grant on mechanisms of sonoporation. Role: Research Sponsor.  Goal: To study biophysical mechanisms of ultrasound-mediated cell poration.

F32HL126421                                     Kopechek (PI)                                                            01/01/15-12/31/17

NRSA Fellowship Grant on ultrasound-mediated modulation of microRNAs for treatment of cardiac hypertrophy. Role: Research Sponsor/Mentor. Goal: To develop targeted ultrasound-mediated miRNA delivery to regress LVH.