Flordeliza S. Villanueva, MD

Research Interests

Dr. Villanueva 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. 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.

 

Selected Publications

Complete List of Published Articles by Dr. Villanueva

 

  1. Villanueva FS, Abraham JA, Schreiner GF, Csikari M, Fischer D, Mills JD, Schellenberger U, Koci BJ, Lee JS. Myocardial contrast echocardiography can be used to assess the microvascular response to vascular endothelial growth factor-121. Circulation. 2002;105(6):759-65. PMID: 11839634.
  2. Weller GE, Lu E, Csikari MM, Klibanov AL, Fischer D, Wagner WR, Villanueva FS. Ultrasound imaging of acute cardiac transplant rejection with microbubbles targeted to intercellular adhesion molecule-1. Circulation. 2003;108(2):218-24. PMID: 12835214.
  3. Weller GE, Wong MK, Modzelewski RA, Lu E, Klibanov AL, Wagner WR, Villanueva FS. Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide arginine-arginine-leucine. Cancer Res. 2005;65(2):533-9. PMID: 15695396.
  4. Pacella JJ, Villanueva FS. Effect of coronary stenosis on adjacent bed flow reserve: assessment of microvascular mechanisms using myocardial contrast echocardiography. Circulation. 2006;114(18):1940-7. PMID: 17060378.
  5. 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.
  6. Villanueva FS, Wagner WR. Ultrasound molecular imaging of cardiovascular disease. Nat Clin Pract Cardiovasc Med. 2008;5 Suppl 2:S26-32. PMID: 18641604.
  7. Moguillansky D, Leng X, Carson A, Lavery L, Schwartz A, Chen X, Villanueva FS. Quantification of plaque neovascularization using contrast ultrasound: a histologic validation. Eur Heart J. 2011;32(5):646-53. PMID: 20581005.
  8. 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.
  9. 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(1):258-62. PMID: 24139920.
  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;16:1-9. PMID: 24742373.
  11. 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.
  12. Pacella JJ, Brands J, Schnatz F, Chen X, Villanueva FS. Treatment of microvascular micro-embolization using microbubbles and long-tone-burst ultrasound: an in vivo study. Ultrasound Med Biol. 2015;41(2):456-64. PMID: 25542487.
  13. 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. PMID: 26603628.
  14. 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.
  15. Kooiman K, van Rooij T, Qin B, Mastik F, Vos HJ, Versluis M, Klibanov AL, de Jong N, Villanueva FS, 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. PMID: 28686673.
  16. 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.