Research Interests
 Platinum drugs are in wide clinical use for the treatment of many different types of cancer. While it is known that the drugs kill cancer cells by attacking cellular targets including DNA, the forms of the drugs that are present in culture media and blood and the mechanism by which the agents enter the cell have not been identified. This information is important for designing new drugs and for improving treatment protocols for those drugs currently in use. We recently found that carbonate, which is ubiquitous in biological systems, reacts with platinum drugs to produce carbonato complexes and these compounds may be some of the platinum species responsible for cell death. In collaboration with J.
Goodisman with our department, we also uncovered a new extracellular defense mechanism which causes some of the platinum carbonato compounds in solution to be modified before they can enter the cell. Since resistant cells modify more platinum than normal cells, this appears to be a hitherto undiscovered mechanism by which cells protects themselves from attack by a platinum drug.
In addition to mechanistic work on the platinum drugs, we are exploring new ways to deliver the drugs to cells with improved specificity. In conjunction with Y.
Luk of our department, we are studying how organic biocompatible nano-assemblies can be used to direct a high flux of drug molecules to target cells. This work involves chemical modification of front line anticancer drugs and their attachment to vehicles that have specific cell recognition properties through antibody-antigen interactions. The resulting conjugates have the potential to target breast cancer and other malignancies.
Selected Publications
Textbook, Dabrowiak, J. C., Metals in Medicine, John-Wiley & Sons, Ltd, Chichester, UK, 2009. » more info
Di Pasqua, A. J.; Wallner, S.; Kerwood, D. J.; Dabrowiak, J. C., Adsorption of the Pt+2 Anticancer Drug Carboplatin by Mesoporous Silica, Chem. Biodivers., 2009, 6, 1343-9.
Di Pasqua, A. J.; Mishler, R. E.; Ship, Y.-L.; Dabrowiak, J. C.; Asefa, T., Preparation of Antibody-Conjugated Gold Nanoparticles, Materials Lett., 2009, 63, 1876-9.
Di Pasqua, A. J.; Centerwall, C. R.; Kerwood, D. J.; Dabrowiak, J. C., Formation of Carbonato and Hydrogencarbonato Complexes in the Reaction of Platinum Anticancer Drugs with Carbonate, Inorg. Chem. 2009, 28, 1192-7.
Sorokanich, R. S.; Di Pasqua, A. J.; Geier, M.; Dabrowiak, J. C., Influence of carbonate on the binding of carboplatin to DNA, Chem. Biodivers. 2008, 5, 1540-44.
Centerwall, C. R.; Kerwood, D. J.; Goodisman, J.; Toms, B. B.; Dabrowiak, J. C., New extracellular resistance mechanism for cisplatin, J. Inorg. Biochem., 2008, 102, 1044-9.
Di Pasqua, A. J.; Sharma, K. K.; Shi, Y.-L.; Tomes, B. B.; Ouellette, W.; Dabrowiak, J. C.; Asefa, T. Cytotoxicity of mesoporous silica nanomaterials, J. Inorg. Biochem., 2008, 102, 1416-23.
Di Pasqua, A. J.; Goodisman, J.; Kerwood, D. J.; Toms, B. B.; Dabrowiak, J. C. Modification of carboplatin by Jurkat cells. J. Inorg. Biochem., 2007, 101, 1438-1441.
Ravera, M.; Bagni, G.; Mascini, M.; Dabrowiak, J. C.; Oscella, D. The activation of platinum (II) antiproliferative drugs in carbonate medium evaluated by means of a DNA-biosensor, J. Inorg. Biochem., 2007, 101, 1023-1027.
Di Pasqua, A. J.; Goodisman, J.; Kerwood, D. J.; Toms, B. B.; Dubowy, R. L.; Dabrowiak, J. C. Role of carbonate in the cytotoxicity of carboplatin. Chem. Res. Toxicol., 2007, 20, 896-904.
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