RESEARCH INTERESTS

• Development of systemically administered plasmid-based gene delivery systems for the treatment of cancer.  Specifically, applications for eliminating brain cancer.  Plasmid DNA formulations are developed that deliver genes to the tumor endothelium.  Therapeutic gene products are then secreted from the endothelium into the adjacent tumors.  Therapeutic genes under investigation include cell cycle inhibitors that prevent the tumor cells and tumor endothelium from proliferating.  These proteins usually reside in the cell. To increase the impact of the cancer gene medicine, the proteins are engineered to be secreted from the transfected cell and diffuse across the membrane into the cytoplasm of the adjacent tumor cell. Using peptides to model these studies, an active moiety has been identified and is being tested for in vivo performance in a brain cancer animal model.  Biochemical and molecular biological technology is being applied to the gene delivery systems to selectively deliver the genes only to the tumor vasculature, thus avoiding expression in non-tumor tissue. The research is being conducted in collaboration with Dr. Ron Mandel, Associate Professor, Department of Neuroscience, University of Florida.  The above research is currently funded through a grant from the J.S.McDonnell Foundation.
• Another active area of research is the development of targeted liposomes with encapsulated conventional drugs targeted to dendritic cells and leukemic stem cells.  Dendritic cells are hypothesized to be the reservoir for latent HIV in AIDS patients.  Current AIDS therapy is a strict dosing regimen that results in reduction of viral load in the blood below detection levels of 100 copies of virus.  However, viral infection returns within two to three months from termination of the therapy.  This is due to the reinfection of T helper cells by the latent viral reservoir. Attachment of ligands to drug delivery systems, such as liposomes, can target these cells and selectively delivery the anti-viral drug to these cells, thus eliminating the reservoir. This same strategy is being applied to treat myeloid leukemic stem cells.  Once again, the purpose is to attack the source of the proliferation.  An antibody raised to the alpha subunit of IL-3 receptor is attached to liposomes with entrapped anticancer drug.  The antibody targets the liposome-laden drugs to the cancer cells and selectively kills these cells. The project is in the in vitro stage of validation.  The project is funded though a donation from Let There Be Hope Foundation, Beverley Hills, CA.
• The final research application is in the area of angiogenesis.  We are part of a larger collaboration with Dr. Maria Grant,  Department of Pharmacology and Therapeutics, University of Florida to apply gene therapy strategies to inhibit retinal revascularization that leads to both diabetic retinopathy and retinopathy of prematurity.  Both gene delivery vehicles and molecular biology approaches to restrict gene expression to proliferating endothelium are being developed.  This research is funded through NIH.

• Drug Delivery (liposome based and polymer based), Gene Therapy, Biochemistry, Biophysics, Pharmacology, Molecular Biology, and Cell Biology.

• Drug Delivery: specifically related to liposomes.
• Drug Development:  Product Discovery, Preclinical Development.
• Areas of Disease:  Cancer, Anti-virals, Arthritis, Angiogenesis

1. Boomer J.A.,  Thompson D.H.,  Sullivan S.M.  “Formation of Plasmid-Based Transfection Complexes with an Acid-labile Cationic Lipid: Characterization of In Vitro and In Vivo Gene Transfer.”  Pharm. Res., (2002) (In Press).
2. Anwer K., Kao G., Proctor B., Anscombe I., Florack V., Earls R., Wilson E., McCreery T., Unger E., Rolland A., Sullivan S.M. “Ultrasound Enhancement of Cationic Lipid Mediated Gene Transfer to Primary Tumors Following Systemic Administration.” Gene Therapy, 7:1833-1839 (2002).
3. Bailey A., Sullivan S.M.  “Ethanol and Calcium Mediated Plasmid Entrapment in Neutral Liposomes.” Biochim Biophys Acta., 1468:239-252 (2002).
4. Anwer K., Meaney C., Kao G., Hussain N., Shelvin R., Earls R.M., Leonard P., Rolland A.P., Sullivan S.M.  “Cationic Lipid-based Delivery System for Systemic Cancer Gene Therapy.” Cancer Gene Therapy, 7(8):1156-64 (2002).
5. Anwer K., Meaney C., Kao G., Shelvin R., Earls R.M., Leonard P., Rolland A.P., Sullivan S.M.  “Optimization of Cationic Lipid/DNA Complexes for Systemic Gene Transfer to Tumor Lesions.”  Journal of DrugTarget, 8(2):125-35 (2000).