Vanderbilt University, B.A., 1970-1974, Math/Chemistry
Emory University, M.D., 1974-1979, Medicine
Emory University Hospital, Residency, 1979-1980, Pediatrics
Emory University Hospital, Residency, 1980-1982, Internal Medicine
Medical Staff Fellow, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 1986-89
Senior Staff and Endocrinology Fellow, Molecular and Cellular Endocrinology Branch, National Institute of Diabetes & Digestive & Kidney Diseases, National Institutes of Health, Bethesda, MD, 1989-94
Research in my laboratory is directed at developing novel gene therapy approaches toward cancer. We have focused on the non-viral delivery of antiangiogenic genes utilizing either in vitro or in vivo model systems. Significant accomplishments in my lab include the following: 1) the first group to deliver the p53 gene systemically in a tumor-bearing model, 2) recognition that antiangiogenesis is the primary mechanism by which gene therapy with p53 inhibits tumor growth, 3) discovery that toxic side effects of non-viral delivery systems can decrease therapeutic gene levels; several companies and laboratories now realize that these side effects are a significant hurdle to overcome, 4) demonstrating that non-viral delivery of "antiangiogenic genes" is effective in tumor-bearing animals; an issued patent for this finding has been awarded, and 5) the recent development of a gene therapy polymer comprised of histidine and lysine (H-K). This polymer either alone or in combination with cationic liposomes increases gene expression markedly compared to liposomes. With further development of the H-K carrier, we plan on coupling the most effective "antiangiogenic gene" and non-viral carrier to inhibit further tumor growth in a mouse model.
Chen, Q.R., Zhang, L., Stass, S.A., and Mixson, A.J.: Branched co-polymers of histidine and lysine are efficient carriers of plasmids. Nucleic Acids Research, 2001, 29(6), 1334-40.
Chen, Q.R., Zhang, L., Gasper, W., and Mixson, A.J.: Targeting tumor angiogenesis with gene therapy. Molecular Genetics and Metabolism, 2001, 74, 120-127.
Chen, Q.R., Zhang, L., Luther, P.W., and Mixson, A.J.: Optimal transfection with the HK polymer depends on its degree of branching and the pH of endocytic vesicles. Nucleic Acids Research, 2002, 30, 1338-1345.
Zhang, L., Gasper, W.J.,Stass, S.A., Ioffe, O.B., Davis, M.A., and Mixson, A.J. : Angiogenic Inhibition Mediated by a DNAzyme That Targets Vascular Endothelial Cell Growth Factor Receptor 2. Cancer Research, 2002; 62, 5463-5469.
Zhang, L., Ambulos, N., and Mixson, A.J.: DNA delivery to cells in culture using peptides. Methods in Molecular Biology, 2004, 245, 33-52.
Zhang, L., Leng, Q., and Mixson, A.J.: Alteration in the IL-2 signal peptide affects secretion of proteins in vitro and in vivo. The Journal of Gene Medicine. 2005, 7, 354-65.
Leng, Q. and Mixson, A.J.: Modified branch peptides with a histidine-rich tail enhance in vitro gene transfection. Nucleic Acids Research, 2005, 33, e40.
Leng, Q., Scaria, P., Zhu, J., Ambulos, N., Campbell, P., and Mixson, A.J.: Highly branched HK peptides are effective carriers of siRNA. The Journal of Gene Medicine, 2005, 7, 977-98.
Leng, Q. and Mixson, A.J.: Small interfering RNA targeting Raf-1 inhibits tumor growth in vitro and in vivo. Cancer Gene Therapy, 2005, 12, 682-90.
Schiffelers, R.M., Mixson, A.J.: Ansari, A.M., Fens, M.H., Tang, Q., Zhou, Q., Xu, J., Molema G., Lu, P.Y., Scaria P.V., Storm G., Woodle M.C.. Transporting silence: Design of carriers for siRNA to angiogenic endothelium. Journal of Control Release. 2005, Epub ahead of print.
Zhu, J, Luther, P.W., Leng, Q, and Mixson, A.J.: Synthetic Histidine-Rich Peptides Inhibit Candida and other Fungi in vitro: Role of Endocytosis and Treatment Implications, Antimicrobial Agents and Chemotherapy. In Press.
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