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2004 Recipient — Oliver Dorigo, MD, PhD

Oliver Dorigo, MD, PhD

Phenotypic and Molecular Effects if Phosphoinositide 3-Kinase (PI3 Kinase)/Akt Pathway Activation in Mouse Ovary Using Conditional Deletion of Tumor Suppressor Gene PTEN

Project Summary

Cancer cells grow due to a range of different mechanisms such as, the over-expression of oncogenes, or genes that cause cancer, or the shutdown of genes encoding tumor suppressors, or genes that stop cancerous growth. The PTEN gene encodes for a protein that suppresses cancer cell growth. Mutations of the PTEN tumor suppressor gene are seen in various malignancies, including brain, endometrial and ovarian cancer. Lack of PTEN results in the activation of a protein, called Akt, which then activates a variety of cell signals that lead to increased ovarian cancer cell growth. But in ovarian cancer cell cultures and animal experiments, inhibition of the Akt pathway, by over-expression of PTEN, results in significant slower tumor growth and cell death.

This project is designed to further elucidate the role of PTEN and the Akt pathways in ovarian cancer by studying Akt activity in the mouse ovary in an animal engineered to be missing the gene for PTEN. Based on previous observations in a prostate tumor model, Dr. Dorigo expects that activation of the Akt pathway in mouse ovarian tissue will result in significant molecular and cellular changes and possible ovarian tumor disease. He will also study changes in protein and gene expression using microarray technology, a method that allows the analysis of many genes simultaneously. The results from this study will provide insight into the Akt regulated signaling events in mouse ovary with the identification of possibly novel genes that are important in the pathogenesis of ovarian cancer.

Areas of Research:

Bio

Oliver Dorigo, MD, PhD, received his medical degree from the University of Heidelberg Medical School in Germany. Following three years of OB/GYN residency training at the University of Munich, Germany, he moved to the Sidney Kimmel Cancer Center in San Diego, CA, to pursue cancer gene therapy research. Dr. Dorigo joined the UCLA Department of OB/GYN in 1995, and completed his residency in 1999. He subsequently received further basic science training with Dr. Arnold Berk at the Molecular Biology Institute at UCLA. As a member of the STAR (Specialty Training and Advanced Research) program, he received his PhD in Molecular Biology in 2003. After completion of his fellowship in Gynecologic Oncology at UCLA/Cedars Sinai Medical Center in 2005, he joined the UCLA Division of Gynecologic Oncology as Assistant Professor. In his own laboratory, Dr. Dorigo’s current work focuses on the development of novel targeted therapy approaches for ovarian cancer, using cell culture systems, human tissues arrays, and mouse models for ovarian cancer. Dr. Dorigo has published extensively in peer-reviewed journals, including the Proceedings of the National Academy of Science, Journal of Immunology, and Journal of Virology. In addition, he is the author of several book chapters in major textbooks.