Dr. Melvin E. Klegerman
The University of Texas Health Science Center at Houston
Department of Internal Medicine - Cardiology
- Molecular Targeting
- Stem Cells
The molecular targeting program of the cardiology research laboratories is focused on liposomal (and other particulate) targeting strategies aimed at developing improved modalities for diagnosis and treatment of cardiovascular and other diseases; molecular aspects of protein-lipid interactions; energetics of non-covalent interactions; molecular strategies for ultrasound imaging enhancement; biochemical, cellular and immunologic mechanisms of atherogenesis; immunochemical and biochemical assay development; and mechanisms of thrombosis and thrombolysis. Cardiology research wet lab facilities on the 5th floor of the new Behavioral and Biomedical Sciences Building (BBSB) on the south campus currently include access to a cell culture module, clinical and research ultrasound instrumentation, animal catheterization laboratory, large animal micro CT, a near infrared fluorescent imaging system, a UV/VIS spectrophotometer, lyophilizers, liquid chromatography and electrophoresis instrumentation, light microscopes, sonicators, table-top and high-speed centrifuges, flow cytometers, microplate readers, fluorescence microscopes and an ultracentrifuge. Our animal research protocols are performed in state-of-the-art facilities on the 6th floor of BBSB, in the adjacent CABIR building and in the Medical School Extension. Computer resources are focused on biomedical engineering applications with an emphasis on imaging algorithms.
Research opportunities for graduate students at the cardiology research laboratory in BBSB 5110 and other locations include 1) in vitro dynamic modeling of targeted echogenic liposome adherence to vessel surfaces, involving a flow circuit with intravascular ultrasound imaging capabilities that aims to test mathematical models of targeted diagnostic and therapeutic delivery vehicles; 2) site-directed stem cell delivery to atheroma in mouse and miniswine models, directed toward the development and optimization of liposome-based strategies enabling the survival, proliferation and trans-differentiation of both hematopoietic and mesenchymal stem cells into vascular endothelial and smooth muscle cells to stabilize vulnerable plaques; 3) development of strategies for delivery of bioactive gases for amelioration of cardiovascular and other pathologies; and 4) a translational research project investigating the safety and efficacy of liposome-encapsulated thrombolytics.
Hamilton, A., Rabbat, M., Jain, P., Belkind, N., Huang, S.L., Nagaraj, A., Klegerman, M., MacDonald, R., and McPherson, D.D.: A Physiologic Flow Chamber Model to Define Intravascular Ultrasound Enhancement of Fibrin Using Echogenic Liposomes. Invest. Radiol. 37:215-21 (2002).
Tiukinhoy-Laing, S.D., Huang, S., Klegerman, M., Holland, CK., and McPherson, D.D.: Ultrasound-Facilitated Thrombolysis Using Tissue-Plasminogen Activator-Loaded Echogenic Liposomes. Thromb. Res. 119:777-84 (2007).
Klegerman, M.E., Huang, S., Parikh, D., Martinez, J., Demos, S.M., Onyuksel, H.A., and McPherson, D.D.: Lipid Contribution to the Affinity of Antigen Association with Specific Antibodies Conjugated to Liposomes. Biochim. Biophys. Acta 1768:1703-16 (2007).
Klegerman, M.E., Zou, Y., and McPherson, D.D.: Fibrin-Targeting of Echogenic Liposomes with Inactivated Tissue Plasminogen Activator. J. Liposome Res. 18:95-112 (2008).
Herbst, S.M., Klegerman, M.E., Kim, H., Shelat, H.S., Wassler, M., Moody, M.R., Yang, C.M., Ge, X., Zou, Y., Clubb, F.J., Kraemer, D.C., Holland, C., McPherson, and D.D.,Geng, Y.J.: Enhancement of stem cell adhesion to porcine aortic endothelium with echogenic liposomes conjugated to antibodies against CD34 and intercellular adhesion molecule-1. Mol. Pharm. 7:3-11 (2010).
Klegerman, M.E., Wassler, M., Huang, S.L., Zou, Y., Kim, H., Shelat, H.S., Holland, C.K., Geng, Y.J., and McPherson, D.D.: Liposomal modular complexes for simultaneous targeted delivery of bioactive gases and therapeutics. J. Control. Rel. 142:326-31 (2010).