• Publications
• Experience
• About

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.

Education

1986	Harvard University	AB	Biochemistry and Molecular Biology, magna cum laude
1991	UCSF	MD	School of Medicine
1991-1992	California Pacific Medical Center, San Francisco	Internship	Internal Medicine
1992-1994	UCSF	Postdoctoral Research Fellowship
1994-1997	UCSF	Resident	Radiation Oncology
1996	UCSF	Chief Resident	Radiation Oncology

Professional Experience

2008-present	UCSF	Professor	Radiation Oncology
2002-2008	UCSF	Associate Professor	Radiation Oncology
1997-2002	UCSF	Assistant Professor	Radiation Oncology
1996-1997	UCSF	Chief Resident	Radiation Oncology

Awards & Honors

1985	Joseph L. Barrett Award for Teaching, Harvard University
1986	Phi Beta Kappa, Harvard University
1986	Thomas T. Hoopes Prize awarded to Senior Honors Thesis
1986	Summa cum laude awarded to Senior Honors Thesis
1991	Alpha Omega Alpha, University of California, San Francisco
1995	ASTRO Basic Scientist Research Award
1995	Junior Scientist Travel Award, 10th International Congress of Radiation Research
1995-1996	American Cancer Society Clinical Oncology Fellowship
1997-1998	Radiological Society of North America Scholar Award
1998	UCSF Dean representative to Association of American Medical Colleges Professional Development Seminar for Junior Women Faculty, Santa Fe, New Mexico
1999	Pfizer Scholars Grant for New Faculty
1999	First place: CAP competition, General Clinical Research Center National Meeting; Arlington, VA
1999	UCSF-Mount Zion Clinical Investigator Award
1999	American Society of Clinical Oncology Career Development Award
2002	Henry J. Kaiser Award for Excellence in Teaching, UCSF School of Medicine
2002	UCSF Nominee for Association of American Medical Colleges (AAMC) Humanism in Medicine Award
2003	Nominated for Teaching Award, UCSF School of Medicine
2004	Nominee: Henry J. Kaiser Award for Excellence in Teaching, UCSF School of Medicine
2005	Selected one of Best San Francisco Doctors for San Francisco Magazine, January 2005
2006	Alpha Omega Alpha, nominated by Medical Student Class of 2007 for AOA membership in the alumni category at UCSF
2007-2008	The Best Doctors in America ®

Publications (Partial Listing, since 2000)

Shu, H-KG; Julin, CM; Furman, F; Yount, GL; Haas-Kogan, DA; Israel, MA. Overexpression of E2F-1 in Glioma-derived Cell Lines Induces a p53-independent Apoptosis that is Further Enhanced by Ionizing Radiation. Neuro-Oncology 2000, 2(1):16-21.

Zundel, W; Schindler, C; Haas-Kogan, DA; Koong, A; Kaper, F; Chen, E; Gottschalk, AR; Ryan, HE; Johnson, RS; Jefferson, AB; Stokoe, D; Giaccia, AJ. Loss of PTEN facilitates Hif-1 mediated gene repression. Genes and Developement, 2000, 14:391-396.

Haas-Kogan DA, Fisch BM, Wara WM, Swift PS, Farmer DL, Harrison MR, Albanese C, Weinberg V, Matthay KK. Intraoperative Radiation Therapy For High Risk Pediatric Neuroblastoma. Int J Rad Onc Bio Phy, 2000, 47(4):985-992.

Bertucio, CS; Wara, WM; Matthay, KK; Johnston, JO; Ablin, AR; Weinberg VK, O’Donnell, RJ; Haas-Kogan, DA. Functional Outcome Of Limb-Sparing Therapy For Pediatric Soft-Tissue Sarcomas of the Extremity. Int J Rad Onc Bio Phy, 2001, 49(3):763-769.

Gottschalk, AR; Basila, D; Wong, M; Dean, NM; Stokoe, D; Haas-Kogan, DA. The PTEN-induced G1 Growth Arrest Requires p27Kip1 and is Independent of p53. Cancer Research, 2001, 61:2105-2111.

Yount GL, Afshar G, Ries S, Korn M, Shalev N, Aldape KD, McCormick, F, and Haas-Kogan DA. Transcriptional Activation of TRADD Mediates p53-independent Radiation-induced Apoptosis of Glioma Cells. Oncogene, 2001, 20:2826-2835.

Haas-Kogan DA, Bristow R, and Maity A. Young Investigators Workshop-Radiation Research Program, Radiation Oncology Sciences Program, National Cancer Institute, NIH, August 1-2, 2000. Int J Rad Onc Bio Phy, 2001, 49(5):1505-1516.

Ermoian RO, Furniss CS, Lamborn DR, Basila D, Berger MS, Gottschalk AR, Nicholas MK, Stokoe DF, Haas-Kogan DA. Dysregulation of PTEN and PKB is Associated with Glioma Histology and Patient Survival. Clinical Cancer Research, 2002, 8(5):1100-1106.

Pore N, Liu S, Haas-Kogan DA, O'Rourke DM, Maity A. PTEN Mutation And Epidermal Growth Factor Receptor Activation Regulate Vascular Endothelial Growth Factor (VEGF) mRNA Expression In Human Glioblastoma Cells By Transactivating The Proximal VEGF Promoter. Cancer Research, 2003, 63(1):236-241.

Haas-Kogan DA, Missett BT, Wara WM, Sarah SS, Lamborn KR, Prados MD, Fisher PG, Huhn SL, Fisch BM, Berger MS and Le QT. Radiation Therapy for Intracranial Germ Cell Tumors. Int J Rad Onc Bio Phy, 2003, 56(2):511-518.

Haas-Kogan, DA, Swift, PS, Selch M, Haase, G, Seeger, RC, Gerbing, RB, Stram,DO, Matthay, KK. Radiotherapy for High-Risk Neuroblastoma: A Children's Cancer Group Study. Int J Rad Onc Bio Phy, 2003, 56(1):28-39.

Hirose Y, Katayama M, Stokoe D, Haas-Kogan DA, Berger MS, Pieper RO. The p38 mitogen-activated protein kinase pathway links the DNA mismatch repair system to the G2 checkpoint and to resistance to chemotherapeutic DNA-methylating agents. Mol Cell Biol. 2003, 23(22):8306-8315.

Pore N, Li B, Shu HK, Li B, Haas-Kogan DA, Stokoe D, Milanini-Mongiat J, Pages G, O’Rourke DM, Bernhard E and Maity A. Sp1 is involved in Akt-mediated induction of VEGF expression through a HIF-1 independent mechanism. Mol Biol Cell, 2004,15(11):4841-4853.

Yount GL, Qian Y, Moore D, Basila D, West J, Aldape K, Arvold N, Shalev N, Haas-Kogan DA. Berberine Sensitizes Human Glioma Cells, but Not Normal Glial Cells, to Ionizing Radiation In Vitro. The Journal of Experimental Therapeutics and Oncology, 2004, J Exp Ther Oncol, 2004, 4(2):137-143.

Gottschalk AR, Doan A, Nakamura JL, Haas-Kogan DA and David Stokoe. Inhibition of PI3 kinase causes cell death through a PKB dependent mechanism and growth arrest through a PKB independent mechanism. Int J Rad Onc Bio Phy, 2005, 61(4):1183-1188.

Nakamura JL, Karlsson A, Arvold ND, Gottschalk AR, Pieper R, Stokoe D, and Haas-Kogan DA. PKB/Akt mediates radiosensitization by the signaling inhibitor LY294002 in human malignant gliomas. J Neurooncol. 2005, 71(3):215-22.

Laprie A, Pirzkall A, Haas-Kogan DA, Cha S, Banerjee A, Barkovich J, Prados MD, Le T, Crawford F, Lu Y, Nelson, S, and McKnight. Longitudinal Multivoxel MR Spectroscopy study of Pediatric Diffuse Brainstem Gliomas treated by Radiotherapy. Int J Rad Onc Bio Phy, 2005; 62(1):20-31.

Arvold ND, Guha N, Wang D, Matli M, Deen DF, Warren RS, and Haas-Kogan, DA. Hypoxia-induced Radioresistance Is Independent of Hypoxia-inducible Factor-1α in Vitro. Int J Rad Onc Bio Phy, 2005; 62(1):207-212.

Haas-Kogan DA, Prados MD, Tihan T, Eberhard DA, Jelluma N, Arvold ND, Baumber R, Lamborn KR, Kapadia A, Malec M, Berger MS, and Stokoe D. Epidermal Growth Factor Receptor, Protein Kinase B/Akt, and Glioma Response to Erlotinib. Journal of the National Cancer Institute, 2005; 97(12):880-887.

Gomez DR, Missett BT, Wara WM, Lamborn KR, Prados MD, Chang S, Berger MS and Haas-Kogan, DA. High failure rate in spinal ependymomas with long-term follow-up. Neuro-Oncology, 2005; 7(3):254-259.

Haas-Kogan, D. A., Prados, M. D., Lamborn, K. R., Tihan, T., Berger, M. S. and Stokoe, D. Biomarkers to predict response to Epidermal Growth Factor Receptor inhibitors. Cell Cycle, 2005, 4(10):95-98.

Mellinghoff IK, Wang Y, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Koji Yoshimoto K, Huang JHY, Chute DJ, Riggs BL, Horvath S, Liau LM, Cavenee WK, Rao N, Beroukhim R, Lee JC, Sellers WR, Stokoe D, Prados M, Cloughesy TF, Sawyers CL, and Mischel PS.  Molecular determinants of EGFR kinase inhibitor response in glioblastoma.  N Engl J Med. 2005; 353(19):2012-24.

Entin-Meer M, Rephaeli A, Yang X, Nudelman A, VandenBerg SR, and Haas-Kogan DA. Butyric acid prodrugs are histone deacetylase inhibitors that show antineoplastic activity and radiosensitizing capacity in the treatment of malignant gliomas.  Mol Cancer Ther. 2005; (12):1952-61.

Rephaeli A, Entin-Meer M, Angel D, Tarasenko N, Gruss-Fischer T, Bruachman I, Phillips DR, Cutts SM, Haas-Kogan DA, Nudelman A. The selectivty and anti-metastatic activity of oral bioavailable butyric acid prodrugs.  Invest New Drugs. 2006, 24:383-392.

Afshar G, Basila D, Furniss S, Yount GL, Arvold ND, Koller E, Haas-Kogan DA. Radiation-induced caspase-8 expression mediates p53-independent apoptosis in glioma cells. Cancer Res. 2006, 66:4223-32.

Tran QNH, Kim AC, Gottschalk AR, Wara, WM, Phillips TL, O'Donnell RJ, Weinberg V, and Haas-Kogan DA. Clinical Outcomes of Intraoperative Radiation Therapy for Extremity Sarcomas, Sarcoma, 2006, 1:1-6.

Mishra KK, Puri DR, Missett BT, Lamborn KR, Prados MD, Berger MS, Banerjee A, Gupta N, Wara MW and Haas-Kogan DA. The role of up-front radiation therapy for incompletely resected pediatric WHO grade II low-grade gliomas. Neuro-oncol. 2006, 8(2):166-74.

Jelluma N, Yan X, Stokoe D, Evan GI, Dansen TB, and Haas-Kogan DA. Glucose withdrawal induces oxidative stress followed by apoptosis in glioblastoma cells but not in normal human astrocytes. Mol Cancer Res. 2006, 4(5):319-30.

Huang K, Haas-Kogan, DA, Weinberg V, and Krieg, R. Higher Radiation Dose with Shorter Treatment Duration Improves Outcome for Locally Advanced Carcinoma of Anal Canal. World J Gastroenterol. 2007, 13(6):895-900.

Entin-Meer M, Yang X, Vandenberg, SR, Lambron KR, Nudelman A, Rephaeli A, and Haas-Kogan DA. In vivo efficacy of a novel histone deacetylase inhibitor in combination with radiation for the treatment of gliomas. Neuro-Oncol. 2007, 9(2):82-88.

Entin-Meer M, Rephaeli A, Yang X, Nudelman A, Nudelman A, and Haas-Kogan DA. AN-113, a novel prodrug of 4-phenylbutyrate with increased anti-neoplastic activity in glioma cell lines. Cancer Letters, 2007, 253(2):205-14.

Wiencke JK, Zheng S, Jelluma N, Tihan T, Lamborn K, Baumber R, Berger MS, Wrensch MR, Haas-Kogan, DA, and Stokoe D.  Methylation of the PTEN promoter in low-grade gliomas contributes to increased PKB Phosphorylation, Neuro-Oncol. 2007, 9(3):271-279.

Gillis AM, Sutton E, DeWitt KD, Matthay KK, Weinberg V, Fisch BM, Chan A, Gooding C, Daldrup-Link H, Wara WM, Farmer DL, Harrison MR and Haas-Kogan DA. Long-term outcome and toxicities of intraoperative radiation therapy for high-risk neuroblastoma. Int J Rad Onc Bio Phys., 2007, 69(3):858-864.

Nakamura JL, Haas-Kogan DA, and Pieper RO. Malignant Glioma Invasion in a Co-Culture System.  Int J Radiat Oncol Biol Phys. 2007, 69(3):880-6.

McBride SM and Haas-Kogan DA. Nutrient-sensitive, antagonistically pleiotropic genes and their contribution to malignant behavior. Med Hypotheses. 2008, 70(2):444-53.

Chen JS, Zhou LJ, Entin-Meer M, Yang X, Donker M, Knight Z, Weiss W, Shokat K, Haas-Kogan DA, and Stokoe D. Characterization of structurally distinct, isoform-selective PI3-kinase inhibitors as radiosensitizing agents in the treatment of human gliomas. Mol Can Therap, in press.

Haas-Kogan DA, Kocak M, Banerjee A, Prados MD, Geyer RJ, Fouladi M, McKnight T, Poussaint TY, Broniscer A, Blaney SM, Boyett JM, and Kun LE. Phase I Trial of Tipifarnib in Pediatric Patients with Newly Diagnosed Non-Disseminated Intrinsic Diffuse Brainstem Gliomas: A Pediatric Brain Tumor Consortium Study. Neuro-Oncol. In press.

Matthay KK, C. Patrick Reynolds CP, Seeger RC, Shimada H, Adkins ES, Haas-Kogan DA, Gerbing RB, London WB, and Villablanca JG. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: A Children’s Oncology Group study. J Clin Oncol, in press.

McBride SM, Daganzo SM, Banerjee A,  Gupta N, Lamborn KR, Prados MD, Berger MS, Wara WM, and Haas-Kogan DA. Radiation is an Important Component of Multimodality Therapy for Pediatric Supratentorial Neuroectoderm Tumors. Int J Rad Onc Bio Phys., in press.

Haas-Kogan DA and Stokoe D. PTEN in Brain Tumors. Expert Review of Neurotherapeutics, in press.

Book Chapters

Margolis LW, Haas-Kogan DA, Meyler TS, Morita ET. What Happens in Radiation Therapy. In: Everyone's Guide to Cancer Therapy, Fourth Edition. Dollinger M, Rosenbaum EH, Tempero M, Mulvihill SJ eds. Kansas City, MO: Andrews McMeel Publishing, 2002.

Billingsley K, Byrd D, Rosenbaum EH, Pellegrini C, Meyler TS, Margolis LW, Dollinger M, Haas-Kogan DA, Mulvihill SJ. Esophagus. In: Everyone's Guide to Cancer Therapy, Fourth Edition. Dollinger M, Rosenbaum EH, Tempero M, Mulvihill SJ eds. Kansas City, MO: Andrews McMeel Publishing, 2002.

Jahan TM, Glassberg AB, Cornett P, Haas-Kogan DA, Anatassiou P, Jablons D. Lung: Nonsmall Cell. In: Everyone's Guide to Cancer Therapy, Fourth Edition. Dollinger M, Rosenbaum EH, Tempero M, Mulvihill SJ eds. Kansas City, MO: Andrews McMeel Publishing, 2002.

Jahan TM, Glassberg AB, Cornett P, Haas-Kogan DA, Anatassiou P, Jablons D. Lung: Small Cell. In: Everyone's Guide to Cancer Therapy, Fourth Edition. Dollinger M, Rosenbaum EH, Tempero M, Mulvihill SJ eds. Kansas City, MO: Andrews McMeel Publishing, 2002.

Weil MD, Haas-Kogan DA, Wara WM. Pediatric Tumors of the Central Nervous System. In: Textbook of Radiation Oncology, Second Edition. Leibel SA, Phillips TL eds. New York, NY: Elsevier Science, Inc. 2003.

Editor: Pediatric Central Nervous System Tumors. Eds. Gupta N, Haas-Kogan DA, Banerjee A, Springer Verlag, Publishers, 2004.

Lieuw KH, Haas-Kogan DA, Ablin A. Intracranial Germ Cell Tumors. In: Pediatric Central Nervous System Tumors, Eds. Gupta N, Haas-Kogan DA, Banerjee A, Springer Verlag, Publishers, 2004.

Tseng TS, Haas-Kogan DA. Craniopharyngioma. In: Pediatric Central Nervous System Tumors, Eds. Gupta N, Haas-Kogan DA, Banerjee A, Springer Verlag, Publishers, 2004.

Haas-Kogan DA, Fisch BM. Advances in Radiation Therapy. In: Pediatric Central Nervous System Tumors, Eds. Gupta N, Haas-Kogan DA, Banerjee A, Springer Verlag, Publishers, 2004.

Matthay KK, Haas-Kogan DA, Constine LS. Neuroblastoma. In: Pediatric Radiation Oncology Eds. Halperin E, Constine L, Tarbell N, Kun L. Lippincott Williams & Wilkins Publishers, Philadelphia, 4th edition. 2004.

Nakamura, JL and Haas-Kogan, DA. PI3 -kinase, PKB/Akt, mTOR and Internal Signaling Pathways. In: Handbook of Brain Tumor Chemotherapy, Ed Newton H. Elsevier Publishing, 2005.

Charolotte DY, Nakamura JL, Haas-Kogan, DA, and Larson, DA. Central Nervous System. In: Hansen EK, Roach MR (Editors). Handbook of Radiation Oncology. New York: Springer, 2006.

Missett B and Haas-Kogan, DA. Small Cell Lung Cancer. In: Hansen EK, Roach MR (Editors). Handbook of Radiation Oncology. New York: Springer, 2006 (in press).

Hansen EK and Haas-Kogan, DA. Non-Small Cell Lung Cancer. In: Hansen EK, Roach MR (Editors). Handbook of Radiation Oncology. New York: Springer, 2006.

Hansen EK and Haas-Kogan, DA. Pediatric (Non-CNS) Tumors. In: Hansen EK, Roach MR (Editors). Handbook of Radiation Oncology. New York: Springer, 2006.

Marcus K and Haas-Kogan, DA. Radiation Therapy. In: Nathan and Oski (Editors) Textbook of Pediatric Hematology and Oncology.

Margolis LW, Haas-Kogan DA, Meyler TS, Morita ET. What Happens in Radiation Therapy. In Everyone’s Guide to Cancer Therapy, Fi Edition. Dollinger M, Rosenbaum EH, Tempero M, Ko A, eds. Kansas City, MO: Andrews McMeel Publishing, 2007.