Germana Rappa, M.D., Ph.D.
Senior Staff Scientist and Associate Professor of Pediatrics
Contact Information:
USA-Mitchell Cancer Institute
1660 Springhill Avenue, Mobile, AL 36607
Telephone: (251) 461-1636
Fax: (251) 460-6994
Email: grappa@usouthal.edu
Background:

Residency, Medical Oncology, National Cancer Institute, Milan, Italy 1986
Research Fellow, Dept. Experimental Oncology, Aviano Cancer Center, Aviano, Italy 1986-1990

Post-doctoral Associate, Dept. of Pharmacology, Yale University Cancer Center, New Haven, CT 1988 & 1990-1991
Junior Research Faculty, Dept. of Pharmacology, Yale University Cancer Center, New Haven, CT 1992-1997
Senior Research Scientist, Norwegian Cancer Center, Oslo, Norway 1997-today
Visiting Professor, USA Mitchell Cancer Institute, USA , Mobile, AL , 2003-2004
Senior Staff Scientist, USA Mitchell Cancer Institute, USA , Mobile, AL, 2005-Present
Research Interests:

Dr. Rappa's work at USA is mainly in the area of preclinical cancer pharmacology, using a gene therapy approach. After the development and study of MRP1 knockout models, the main research focus is now on the design of drug resistance-expressing retroviral vectors to protect the bone marrow of cancer patients from collateral toxicity of chemotherapy. To this aim, in vitro and in vivo models based on bone marrow stem/progenitor cells, are being developed, and new anticancer drug strategies tested.

Selected Recent Publications :
Rappa, G. , Lorico, A., Liu, M-C., Kruh, G. D., Cory, A. H., Cory, J. G., and Sartorelli, A. C. Overexpression of the multidrug resistance genes MDR1, MDR3 and MRP in L1210 leukemia cells resistant to inhibitors of ribonucleotide reductase. Biochem. Pharmacol., 54: 649-655 (1997).

Rappa, G. , Lorico, A., Flavell, R. A., and Sartorelli, A. C. Evidence that the multidrug resistance protein (MRP) functions as a co-transporter of glutathione and natural product toxins. Cancer Res., 57: 5232-5237 (1997).

Lorico, A., Rappa, G. , Finch, R. A., Yang, D., Flavell, R. A., and Sartorelli, A. C. Disruption of the murine MRP (multidrug resistance protein) gene leads to increased sensitivity to etoposide (VP-16) and increased levels of glutathione. Cancer Res., 57: 5238-5242 (1997).

Rappa, G. , Murren, J.R., Johnson, L.-M., Lorico, A., and Sartorelli, A.C. Novobiocin-Induced VP-16 Accumulation and MRP Expression in Human Leukemia and Ovarian Carcinoma Cells. Anticancer Drug Des. Apr;15(2):127-34 (2000).

Murren, J.R., Di Stasio, S.A., Lorico, A., Mc Keon, A., Zuhowski, E.G., Egorin, M.J., Sartorelli, A.C., and Rappa, G. Phase I and Pharmacokinetic Study of Novobiocin in Combination with VP-16 in Patients with Refractory Malignancies. The Cancer Journal 6, 256-265, 2000.
Rappa, G. , Shyam, K., Lorico, A., Fodstad, O., and Sartorelli, A. C. Structure-activity studies of novobiocin analogs as modulators of VP-16 cytotoxicity. Oncology Research, 12, 113-119, 2001.
Rappa, G. , Lorico, A., Hildinger, M., Fodstad, O., and Baum C. Novel Bicistronic Retroviral Vector Expressing ?-Glutamyl Cysteine Synthetase And The Multidrug Resistance Protein 1 (MRP1) Protects Cells From MRP1-Effluxed Drugs And Alkylating Agents. Human Gene Therapy, 12: 1785-96. 2001
Lorico, A., Nesland, J., Emilsen, E., Fodstad, O., and Rappa, G. Role of the Multidrug Resistance Protein 1 (MRP1) gene in the carcinogenicity of aflatoxin B1: investigations using mrp1-null mice. Toxicology 171, 201-205, 2002.
Lorico, A., Bertola, A., Baum, C., Fodstad, O., and Rappa, G. Role of the Multidrug Resistance Protein 1 (MRP1) in protection from heavy metal oxyanions: investigations in vitro and in MRP1-deficient mice. Biochem Biophys Res Commun. 291: 617-622, 2002 .

Rappa, G. , Gamcsik, M P., Mitina, R. L., Baum, C., Fodstad, O. and Lorico A. Retrovirus-Mediated Transfer of the Human Multidrug Resistance Protein 1 (MRP1) cDNA leads to decreased intracellular glutathione and hypersensitivity to L-buthionine-R, S-sulfoximine (BSO). Eur. J. Cancer, 39, 120-128, 2003.

Rappa, G. , Kunke, D., Holter, J., Diep, D. B., Meyer, J., Baum, C., Fodstad, O., Krauss, S., and Lorico, A. Efficient expansion and gene transduction of mouse neural stem/progenitor cells on recombinant fibronectin. Neuroscience, in press.
Lorico, A., Bratbak, D., Meyer, J., Kunke, D., Krauss, S., Baum, C., Fodstad, O., and Rappa, G. g-glutamyl cysteine synthetase and L-buthionine-S,R-sulfoximine (BSO): a new selection strategy for gene-transduced neural and hematopoietic stem/progenitor cells. Gene Therapy, submitted.

USA Mitchell Cancer Institute

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