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Todd Giorgio

Professor of Biomedical Engineering
Professor of Chemical and Biomolecular Engineering
Professor of Cancer Biology

Biomedical Engineering
Chemical and Biomolecular Engineering

Intellectual Neighborhoods

Research Focus

Protease-responsive biosensors for siRNA and drug delivery in vitro and in vivo, advanced materials for immunomodulation devices for sepsis treatment.

Current Projects

Description of Research Program: 
The characterization of many interesting and important problems in biology and medicine demands rapid, perhaps continuous, measurements conducted on single cells. Our research team seeks to develop quantitative analytical and calculational tools used to understand fundamental cellular behavior. The application of these tools, which are primarily optical techniques, to the solution of significant problems in mammalian systems is our overall aim.

The practical application of human gene therapy delivered by cationic liposome vehicles has been limited by insufficient transgene synthesis. Our group is working toward identification of the key regulatory events in intracellular plasmid delivery and processing. We use our results to design and test specific, directed modifications of the gene delivery process for optimization of transgene synthesis.

Understanding the cellular roles in vascular disease and post-angioplasty restenosis is critical to the development of successful clinical interventions. The relatively uncontrolled conditions of most in vivo studies, however, often leads to difficult interpretation of the measurements obtained by these techniques. Our team seeks to characterize platelet-leukocyte-endothelial cell interactions in an in vitro model of vascular damage which includes controlled fluid shear forces to test and develop antithrombotic strategies.

Current Projects include:

  1. In a single cell, how is intracellular plasmid copy number related to transgene expression?
  2. What mechanisms are responsible for cellular binding and incorporation of cationic liposome/plasmid complexes?
  3. How does intracellular processing of delivered plasmid modulate transgene expression?
  4. What is the significance of platelet activation in the fluid suspension in modulating platelet and leukocyte adhesion to vascular damage?
  5. Which lymphocytes form platelet conjugates and adhere to vascular damage during exposure to fluid shear stress?
  6. What is the role of lymphocyte-platelet conjugates in the cellular response to vascular damage?

Environmentally sensitive contrast agents for imaging proteolytic activity in human pathologies. 
Over the past decade, a substantial body of research has produced a wide range of nanoscale contrast agents for interrogating microenvironments specific to human pathologies of interest, such as atherosclerosis and cancer. In these two cases, passive targeting of the contrast agents to sites of disease has been achieved through the enhanced permeation and retention (EPR) effect, while active targeting has been achieved using methods such as the immobilization of antibodies, peptides, or other ligands on nanoparticles.

In order to achieve further site specificity, we are working on developing novel nanomaterials that respond in the presence of specific microenvironments, such as the proteolytic environment in tumors. Our active projects seek to achieve this goal on quantum dots, dendrimers, gold nanoparticles, and iron oxide nanoparticles, in order to develop a nanoparticle toolbox for use with a wide range of imaging modalities.

Researchers: Bell, Lowery, Ortega, Scherer, Yu

Maximizing PEGylation, ligand loading on nanoparticle platforms. 
The advantages of using nanoparticles for in vivo delivery of a contrast agent or a bioactive moiety or drug include, among many, the high surface-to-volume ratios achievable on nanoparticle platforms. As a result of the high surface areas, sensitivity of a targeted agent for its destination is greatly increased. A good deal of this sensitivity depends on the ability to construct nanoparticles with high surface densities of reactive groups onto which ligands, drugs, and molecules of interest can be tethered. Nanoparticle multivalence can greatly enhance its ability to bind to targets with great avidity and sensitivity.

Here, with the nonbiofouling polymer polyethylene glycol (PEG) as a model ligand and gold nanoparticles as the substrate, we are investigating grafting conditions that can lead to optimum ligand loading of nanoparticle platforms.

Researchers: Bell

Publications

Tseng W, Haselton, FR and Giorgio TD: Mitosis activates transgene expression of plasmid delivered by cationic liposomes. Biochimica Biophysica Acta 1999, 1445, 53-64.

Mehta A, Haselton FR and Giorgio TD: Quantitative estimation of binding sites for cationic liposomes in mammalian endothelial cells. Biochimica Biophysica Acta 1998, [in review].

Tseng W, Haselton, FR and Giorgio TD: Transfection by cationic liposomes using simultaneous single cell measurements of plasmid delivery and transgene expression. Journal of Biological Chemistry1997, 10 October, 25641-25647.

Montero GA, Giorgio TD and Schnelle KB: Supercritical fluid extraction of contaminated soil. The Journal of Environmental Science and Health 1997,A32, 481-495.

Tseng W, Purvis NB, Haselton FR and Giorgio TD: Cationic liposomal delivery of plasmid to endothelial cells measured by quantitative flow cytometry.  Biotechnology and Bioengineering 1996,50, 548-554.

Montero GA, Giorgio TD and Schnelle KB: Scale-up and economic analysis for the design of supercritical fluid extraction equipment for remediation of soil.  Environmental Progress  1996, 15, 112-121.

Giorgio TD and Yek SH: The effect of bilayer composition on calcium ion transport facilitated by fluid shear stress. Biochimica Biophysica Acta 1995, 1239, 39-44.

Rozga J, Morsiani E, LePage E, Moscioni AD, Giorgio T and Demetriou AA: Isolated hepatocytes in a bioartificial liver: a single group view and experience. Biotechnology and Bioengineering 1994, 43, 645-653.

Purvis NB, Giorgio TD, Stelzer, GT and Shults, KE: Shear-induced platelet activation measured by flow cytometry. Annals of the New York Academy of Sciences 1994, 714, 309-311.

Purvis NB and Giorgio TD: Cell size and surface area determined by flow cytometry. Annals of the New York Academy of Sciences 1994, 714, 306-308.

Tseng W, Haselton, FR and Giorgio TD: Transfection by cationic liposomes using simultaneous single cell measurements of plasmid delivery and transgene expression. Journal of Biological Chemistry 1997, 272, 25641-25647.

Tseng W, Haselton, FR and Giorgio TD: Mitosis activates transgene expression of plasmid delivered by cationic liposomes. Biochimica Biophysica Acta 1999, 1445, 53-64.

James M and Giorgio TD: Nuclear-associated plasmid, but not cell-associated plasmid, is correlated with transgene expression in cultured mammalian cells. Molecular Therapy 2000, 1, 339-346. [Commentary in Leopold PL: Fluorescence methods reveal intracellular trafficking of gene transfer vectors: The light toward the end of the tunnel. Molecular Therapy 2000, 1, 302-303.]

Hallahan DE, Qu S, Geng L, Cmelak A, Chakravarthy A, Martin W, Scarfone C, Giorgio T: Radiation-mediated control of drug delivery. American Journal of Clinical Oncology 2001, 24, 473-480.

Hallahan DE, Geng L, Qu C, Scarfone S, Giorgio T, Donnelly E, Gao X, Clanton J: Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels. Cancer Cell 2003, 3, 63-74.

Pfeiffer S, Zorn GL, Zhang JP, Farley SM, Giorgio TD, Robson SC, Azimzadeh AM and Pierson RN: Hyperacute lung rejection in the pig-to-human model: platelet receptor inhibitors synergistically modulate complement activation and lung injury. Journal of Transplantation 2003, 75, 953-959.

Banks GA, Roselli RJ, Chen R and Giorgio TD: A model for the analysis of nonviral gene therapy. Gene Therapy 2003, 10, 1766-1775.

Smith RA and Giorgio TD: Quantitation and kinetics of CD51 surface receptor expression: implications for targeted delivery. Annals of Biomedical Engineering 2004, 32, 635-644.

Smith RA and Giorgio TD: Cell-based screening: a high throughput flow cytometry platform for identification of cell-specific targeting molecules. Combinatorial Chemistry and High Throughput Screening 2004, 7, 141-151.

Harris SS and Giorgio TD: Convective flow increases lipoplex delivery rate to in vitro cellular monolayers. Gene Therapy 2005, 12, 512-520.

Kuhn SJ, Hallahan DE and Giorgio TD: Characterization of superparamagnetic nanoparticle interactions with extracellular matrix in an in vitro system. Annals of Biomedical Engineering 2006, 34, 51-58.

Kuhn SJ, Finch SK, Hallahan DE and Giorgio TD: Proteolytic surface functionalization enhances in vitro magnetic nanoparticle mobility through extracellular matrix. NanoLetters 2006, 6, 306-312.