Nenad Petrovic
Lecturer in Pharmacogenomics
Qualifications
BS (Hons) Belgrade, MS Belgrade, PhD University of New York, USA
Contact Detalis
University of Sydney
Tel: +61 2 9036 3360
Fax: +61 2 9036 3139
Email:
Room 103 (Pharmacogenomics)
K25 - Medical Foundation Building
92 Parramatta Road
Camperdown NSW 2050
Short Resume
- PhD: State University of New York, USA
- Postdoctoral Researcher: Roswell Park Cancer Institute, Buffalo, NY USA
- Research A/Prof: Medical College of Pennsylvania, Philadelphia, PA USA
- Research Officer: University of Western Australia, Perth, Australia
- Research A/Prof: University of Connecticut, Hartford, CT USA
Research Interests
At USYD Dr Petrovic has developed active research program investigating dietary regulation of tumour angiogenesis and metastasis by omega-3 polyunsaturated fatty acids. This research includes development of new in vitro models involving human endothelial cells as well as in vivo mouse models of angiogenesis, directed tumorigenesis and metastasis. Effects of dietary fats on cancer risk and progression are attracting considerable interest within the community. Both epidemiologic and experimental findings indicate that the omega-3 polyunsaturated fatty acids (φ-3 PUFA), almost absent in typical Western diets today, exert protective effects against cancers. Since the mechanisms by which these fats suppress cancer are still unknown, further research in this area is needed. One of the potential targets for φ-3 PUFA effects on carcinogenesis is angiogenesis, a process of new blood vessel formation within rapidly growing tumour. Extent of tumour angiogenesis is one of the major factors affecting cancer progression and patient mortality. In our preliminary studies using human vascular endothelial cells in vitro we have determined that φ-3 PUFA affect all major pro-angiogenic cellular processes, namely cell activation, migration (also the main process affecting tumour metastasis) and protease secretion. Future research is designed to further expand our in vitro studies using animal models of angiogenesis and metastasis in vivo. Subsequent projects will be directed toward identifying the most effective ω-3 PUFA and their derivatives that could be used as potential anticancer therapeutics.

Second research direction that is developing is related to the investigation of cytochrome P450 1A2 (CYP1A2) genetic polymorphism and in Australian population affecting induction and expression of this gene. The CYPs are monooxygenases which catalyse many reactions involved in drug metabolism of which CYP1A2 is an important member. Inter-individual differences in human CYP1A1 expression appear to be associated with variability in risk toward various types of environmental toxicity and cancer. Several studies have indicated the presence of wide inter-individual and ethnic differences in CYP1A2 levels affecting metabolism of various drugs. Future projects are designed to investigate genetic variability of CYP1A2 in Australian population and to correlate these differences with CYP1A2 expression.

Recent Research Publications
CONCOMITANT ACTIVATION OF EXTRACELLULAR SIGNAL-REGULATED KINASE AND INDUCTION OF COX-2 STIMULATES MAXIMUM PROSTAGLANDIN E2 SYNTHESIS IN HUMAN AIRWAY EPITHELIAL CELLS
Petrovic N, Knight D, Bomalaski J, Thompson P, and Misso N. Prostaglandins and Other Lipid Mediators (2006, in press)
PROSTATE-SPECIFIC MEMBRANE ANTIGEN REGULATES ANGIOGENESIS BY MODULATING INTEGRIN SIGNAL TRANSDUCTION
Conway RE, Petrovic N, Li Z, Heston W, Wu D and Shapiro LH. (2006) Mol. Cell. Biol. 26: 5310-5324
This report has been chosen by the editor of Science as the “pick of the week” paper in cell biology in July 2006
AMINOPEPTIDASE N (CD13)
Petrovic N, Schacke W and Shapiro LH (2005) Nature Mol Pages (invited review)
CD13/AMINOPEPTIDASE N IN TUMOUR GROWTH AND ANGIOGENESIS
Petrovic N, Shacke W and Shapiro LH. Invited book chapter in Aminopeptidases in Biology and Disease (Kluwer Plenum Publishers, London) (2004)
αVβ3 INTEGRIN INTERACTS WITH THE TGF β TYPE II RECEPTOR TO POTENTIATE THE PROLIFERATIVE EFFECTS OF TGF β 1 IN LIVING HUMAN LUNG FIBROBLASTS
Scaffidi KA, Petrovic N, Moodley PY, Fogel-Petrovic M, Kroeger MK, Seeber RM, Eidne KA, Thompson PJ and Knight DA. (2004) J Biol Chem 27: 37726-37733
CD13/APN TRANSCRIPTION IS INDUCED BY RAS/MAPK MEDIATED PHOSPHORYLATION OF ETS-2 IN ACTIVATED ENDOTHELIAL CELLS
Petrovic N, Bhagwat SV, Ratzan WJ, Ostrowski MC and Shapiro LH. (2003), J Biol Chem 278: 49358–49368
THE ANGIOGENIC REGULATOR CD13/APN IS A TRANSCRIPTIONAL TARGET OF RAS SIGNALING PATHWAYS IN ENDOTHELIAL MORPHOGENESIS
Bhagwat SV, Petrovic N, Okamoto Y, and Shapiro LH. (2003) Blood 101: 1818-1826
CRITICAL ROLES OF A CYCLIC AMP RESPONSIVE ELEMENT AND AN E-BOX IN REGULATION OF MOUSE RENIN GENE EXPRESSION
Pan L, Black TA, Shi Q, Jones CA, Petrovic N, Loudon J, Kane C, Sigmund CD, Gross KW. (2001) J Biol Chem. 276: 45530-45538
A SIMPLE ASSAY FOR A HUMAN SERUM PHOSPHOLIPASE A2 THAT IS ASSOCIATED WITH HIGH-DENSITY LIPOPROTEINS
Petrovic N, Grove C, Langton P, Misso N and Thompson PJ (2001) J Lipid Res 42: 1706-1713