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Roach, Mack [Chair]Barani, IgorChang, AlbertFogh, ShannonFowble, BarbaraGottschalk, AlexanderHaas-Kogan, DaphneHsu, I-Chow (Joe)Larson, DavidMishra, KavitaNakamura, JeanPark, CatherineQuivey, JeanneSethi, RajniSneed, Patricia (Penny)Yom, Sue
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Doctor's Picture

Daphne Adele Haas-Kogan

M.D.

Professor of Radiation Oncology and Neurological Surgery
Program Director and Vice Chair, Department of Radiation Oncology

Helen Diller Family Comprehensive Cancer Center
Box 1708, 1600 Divisadero St, MZ Bldg R H1031
San Francisco, CA 94115
Phone: 415/353-7175 Fax: 415/353-9883
Email: DHaasKogan[at]RadOnc.ucsf.edu

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Professional Focus

Dr. Haas-Kogan's research interests have focused on dissection of the molecular pathogenesis of brain tumors and the cellular response to ionizing radiation. Glioblastoma Multiforme (GM), the highest grade malignant glioma, is a brain tumor that is nearly uniformly fatal. The most common genetic alteration in GM tumors is loss of heterozygosity of chromosome 10q, which is seen in approximately 90% of tumors. PTEN is a tumor suppressor gene that maps to chromosome 10q23. It is mutated in GM tumors as well as in a myriad of additional human malignancies. The research team has recently reported that PTEN regulates the activity of the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB) pathway, a signaling cascade implicated in cancer development. PTEN mutations in GM cell lines lead to increased, dysregulated PKB activity. Since PTEN mutations have been identified in many human malignancies, including 20-40% of GM tumors, the data implicate dysregulation of the PI3K/PKB pathway as a key mediator of human carcinogenesis.

Dr. Haas-Kogan seeks to define how PTEN mutations contribute to the pathogenesis of GM tumors and explore the therapeutic potential of gene-therapy approaches designed to target the dysregulated PI3K/PKB pathway. In the laboratory component of their work the team is exploring the mechanism by which PTEN arrests cell cycle progression in G1 phase and increases protein expression of the cdk inhibitor p27Kip1. In the translational portion of the research they are attempting to define the clinical relevance of PTEN mutations in primary GM tumors. Furthermore, they are currently evaluating the in vivo anti-neoplastic activity of therapies designed to inhibit the PI3K/PKB signal transduction pathway. Dysregulation of the PI3K/PKB cascade in a large proportion of GM tumors establishes this pathway as an important target for therapeutic intervention. The hope is that these studies may allow the use of PTEN and the PI3K/PKB signal transduction cascade as a molecular point of intervention in the treatment of GM tumors.

In a parallel project the research team is investigating the underpinnings of the molecular response to ionizing radiation. Using cDNA expression arrays they have reported that components of the TNF-signaling pathway, TRADD and caspase 8, are transcriptionally activated by radiation in glioma tumors and play an important role in p53-independent apoptosis. Through these complementary lines of investigation they hope to identify molecular targets for novel gene therapies as well as improve standard treatments for glioma tumors, such as ionizing radiation.

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