» Research Group web page		James Dabrowiak  Professor Bioinorganic chemistry; biophysics jcdabrow@syr.edu phone: 315-443-4601 / fax: 315-443-4070 Office: CST 2-016D Education: • B.S., 1965, Purdue University • Ph.D., 1970, Western Michigan University • Postdoctoral Research Associate, 1970-1972, Ohio State University Honors & Awards: • American Cancer Society Scholar, 1985 Courses: • CHE 412/612*: Metals in Medicine • CHE 474/674: Structural and Physical Biochemistry • CHE 600: Bioinorganic Chemistry-Nucleic Acids   * denotes current Spring '08 course

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 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, readily reacts with platinum drugs to produce carbonato complexes and these compounds may be 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. Understanding how this mechanism works will be important for ultimately overcoming the resistance that occurs in platinum chemotherapy.

We have also been studying new ways to deliver platinum drugs to cells using nano-technology. In collaboration with T. Asefa of our department we are exploring if and to what extent inorganic mesoporous silica can be used as a high capacity vehicle for delivering toxic drugs to cells. Since equipping mesoporous silica with antibodies results in an assembly that is specific for a certain type of cell, this approach holds promise for directing a high payload of an active drug to a cancer cell. Additional studies with T. Asefa, are directed at constructing gold nano-particle sensors for rapidly detecting common pathogens such as E.coli and salmonella under environmental conditions. In addition to mesoporous silica, other types of newly discovered nano scale structures hold promise for cancer chemotherapy. In conjunction with Y. Luk of our department, we are studying how organic biocompatible nano-assembles can be used to direct a high flux of drug molecules to target cells, This work involves chemical modification of the front line anticancer drug carboplatin and its attachment to vehicles that have specific cell recognition properties through antibody-antigen interactions. The resulting conjugate has the potential to target breast cancer and other malignancies.

Selected Publications Sorokanich, R. S.; Di Pasqua, A. J.; Geier, M.; Dabrowiak, J. C., Influence of carbonate on the binding of carboplatin to DNA, Chem. Biodivers. Submitted. Centerwall, C. R.; Kerwood, D. J.; Goodisman, J.; Toms, B. B.; Dabrowiak, J. C., New extracellular resistance mechanism for cisplatin, J. Inorg. Biochem., 2008, in press. 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, in press. 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.; Dabrowiak, J. C. Modification of carboplatin by Jurkat cells. J. Inorg. Biochem., 2007, 101, 1438-1441. 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. Binter, A.; Goodisman, J.; Dabrowiak, J.C. Formation of monofunctional cisplatin-DNA adducts in carbonate buffer. J. Inorg. Biochem., 2006, 100, 1219-1224. Centerwall, C. R.; Tacka, K. A.; Kerwood, D. J.; Goodisman, J.; Toms, B. B.; Dubowy, R. L.; Dabrowiak, J. C. Modification and uptake of a cisplatin carbonato complex by Jurkat cells. Mol. Pharmacol., 2006, 70, 348-355. DiPasqua, A. J.; Goodisman, J.; Kerwood, D. J.; Toms, B. B.; Dubrowy, R. L.; Dabrowiak, J. C. Activation of carboplatin by carbonate. Chem. Res. Toxicol., 2006, 19, 139-149. On of the top 20 accessed articles of 2006 in, Chem. Res. Toxicol. » View all Publications