Department of Radiation Oncology

Ann R. Kennedy, D.Sc
PROGRAM DIRECTOR

Mechanisms for the enhancement and suppression of radiation carcinogenesis by modifying agents; Mechanisms for the suppression of oxidative stress induced by the types of radiation encountered during travel in space.

• Kennedy, A.R., Ware, J.H., Guan, H. Donahue, H.H., Biaglow, J.E., Zhou, Z., Stewart,J., Vazquez, M. and Wan, X.S. Selenomethionine protects against adverse biological effects induced by space radiation. Free Radiation Biology and Medicine 236: 259-266, 2004.
• Wan, X.S., Ware, J.H., Zhou, Z., Donahue, J.J.., Guan, J. and Kennedy, A.R.  Protection against radiation-induced oxidative stress in cultured human epithelial cells by treatment with antioxidant agents.  Int. J. Radiat. Oncol. Bio. Phys. 64(5): 1475-1481, 2006.

Steven H. Hahn, M.D.

Evaluation of signal transduction inhibitors as clinical radiosensitizers; Photodynamic therapy for prostate cancer and for serosal malignancies; Evaluation of the tumor microenvironment in glioma patients using F-18 EF5 and MRI.

• Hahn SM, Fraker, DL, Mick, R, Metz, J, Busch, TM, Smith, D, Zhu, T, Rodriguez, C, Dimofte, A, Spitz, F, Putt, M, Rubin, SC, Menon, C, Wang, H-W, Shin, D, Yodh, A, and Glatstein E.  A Phase II Trial of Intraperitoneal Photodynamic Therapy for Patients with Peritoneal Carcinomatosis and Sarcomatosis.  Clin Cancer Res,  April 15, 2006 In Press. 
• Martin, N.E., Brunner, T.B., Kiel, K.D., DeLaney, T.F., Regine, W.F., Mohiuddin, M., Rosato, E.F., Haller, D.G., Stevenson, J.P., Smith, D.,, Pramanik, B., Tepper, J., Tanaka, W.K., Morrison, B., Deutsch, P., Gupta, A.K., Muschel, R.J., McKenna, W.G., Bernhard, E.J., and Hahn, S.M.  A Phase I Trial of the Dual Farnesyltransferase and Geranylgeranyltransferase Inhibitor L-778,123 and Radiotherapy for Locally Advanced Pancreatic Cancer.  Clin Cancer Res 10:5447-5454, 2004.

Theresa M. Busch, Ph.D.  

Photodynamic therapy (PDT) as cancer therapy:  Characterization of PDT effect on tumor microenvironment; Mechanisms inolved in efficacy of Photodynamic therapy.

• Busch TM, Hahn SM, Wileyto EP, Koch CJ, Fraker DL, Zhang P, Putt M, Gleason K, Shin DB, Emanuele MJ, Jenkins K, Glatstein E, Evans SM. Hypoxia and Photofrin uptake in the intraperitoneal carcinomatosis and sarcomatosis of photodynamic therapy patients. Clin. Cancer Res. 10: 4630¡V4638, 2004.
• Yu G, Durduran T, Zhou C, Wang HW, Putt ME, Saunders M, Sehgal CM, Glatstein E, Yodh AG, Busch TM. Noninvasive monitoring of murine tumor blood flow during photodynamic therapy provides early assessment of treatment efficacy. Clin Cancer Res. 11:3543-52, 2005.

Wafik S. El-Deiry, M.D., Ph.D.

Pathways of radiation-induced cell death; Determinants of TRAIL resistance; Mechanism of tumor suppression by BRACA1; c-Myc targets in cell cycle deregulation, apoptosis and transformation.

• Dash, B.C., and El-Deiry, W.S. G2/M-dependent phosphorylation of p21 promotes assembly and cdc2 kinase activity. Mol. Cell. Biol., 25:3364-3387, 2005.
• Finnberg, N., Gruber, J.J., Fei, P., Rudolph, D., Bric, A., Burns, T.F., Ajuha, H., Page, R., Wu, G.S., Chen, Y., McKenna, W.G., Bernhard, E.J., Lowe, S.W., Mak, T.W., and El-Deiry, W.S. DR5 knock-out mice are compromised in radiation-induced apoptosis. Mol. Cell. Biol., 25:2000-13, 2005.

Sydney M. Evans, V.M.D.

Mechanisms of treatment resistance in human cancers.

• Evans, S. M., Fraker, D. L., Hahn, S. M., Gleason, K., Jenkins, W. T., Jenkins, K., Hwang, W.-T., Zhang, P., and Koch, C. J. EF5 Binding and Clinical Outcome in Human Soft Tissue Sarcomas. International J. Radiation Oncology, Biology and Physics, 2006 (in press).
• Evans, S., Judy, K. D., Dunphy, I., Jenkins, W. T., Hwang, W.-t., Nelson, P. T., Lustig, R. A., Jenkins, K., Magarelli, D. P., Hahn, S. M., Collins, R. A., Grady, M. S., and Koch, C. J. Hypoxia is Important in the Biology and Aggression of Human Glial Brain Tumors. Clinical Cancer Research 10: 8177-8184, 2004.

Jeffrey M. Field, Ph.D.

Signal transduction pathways involved in carcinogenesis; Mechanisms of p53 mutagenesis.

• Fryer B.H., Vedantam S.L., Wang C.H., Zhou G.L., Jin S.H., Fletcher L., and Field J. (2006 )PKG Phosphorylates Pak1, Inhibiting Pak/Nck binding and Stimulating Pak/VASP Association J. Biol. Chem, In press.
• Yu, D., Berlin, J.A., Penning, T.M., Field, J.M. (2002) Reactive oxygen species generated by PAH o-quinones cause change-in-function mutations in p53. Chem. Res. Toxicol. 15: 832-842. (Profiled on front cover)

Marcelo G. Kazanietz, Ph.D.

PKC and the regulation of apoptotic responses in prostate carcinogenesis;  Regulation of the Rac pathway;   Chimaerins: novel DAG/phorbol esters with Rac-GAP activity;  Activation of ErbB.

• Wang, H., Yang, C., Coluccio Leskow, F., Sun, J., Canagarajah, B., Hurley, J.H., and Kazanietz, M.G. Phospholipase C/diacylglycerol-dependent activation of 2-chimaerin restricts EGF-induced Rac signaling. EMBO J., in press (2006).
• Gonzalez-Guerrico, A., Meshki, J., Xiao, L., Benavides, F., Conti, C.J., and Kazanietz, M.G. Molecular mechanisms of protein kinase C-induced apoptosis in prostate cancer cells. J. Biochem. Mol. Biol. 38: 639-645 (2005).

Gary D. Kao, M.D., Ph.D.

Novel mechanisms mediating cancer cell cytotoxicity, especially through G2/M checkpoint regulation or through the regulation of gene expression and chromatin remodeling; Novel models for testing the effects of chemo-radiation and modifiers on vertebrate embryonic viability and development; Histone deacetylases (HDACs) as a therapeutic target. 

• Kim M, Murphy K, Liu F, Parker S, Dowling ML, Baff W, Kao GD.  Caspase-mediated specific cleavage of BubR1 is a determinant of the mitotic spindle checkpoint.  Molecular and Cellular Biology,  25(21):9232-48, 2005.
• Liu F, Pore N, Kim M, Voong KR, Dowling M, Maity A, Kao GD.  Regulation of Histone Deacetylase 4 Expression by the SP Family of Transcription Factors.  Molecular Biology of the Cell. Feb;17(2):585-97, 2006.

Cameron J. Koch, Ph.D.

Biochemical and genetic basis for therapy resistance of hypoxic tumor cells; The importance of hypoxia in normal tissues.

• Ayene, I.S., Ford, L.P., Koch, C.J. Ku protein targeting by Ku70 small interfering RNA enhances human cancer cell response to topoisomerase II inhibitor and gamma radiation. Mol. Cancer Therapeutics, 4: 529-536, 2005.
• Ayene, I.S., Stamato, T.D., Mauldin, S.K., Biaglow, J.E., Tuttle, S.W., Jenkins, S.F. and Koch, C.J. Mutation in glucose-6-phosphate dehydrogenase gene leads to inactivation of Ku DNA end binding during oxidative sress. J. Biol. Chem., 277:9929-9935, 2002.

Amit Maity, M.D., Ph.D.

Regulation of VEGF/HIF-1alpha by the PI3K/Akt pathway;  Modulation of radiosensitivity by inhibition of the PI3K/Akt pathway;  Tumor sensitization by the HIV protease inhibitor nelfinavir.

• Pore, N, Liu, S, Shu, H-S, Li, B, Haas-Kogan, D, Stokoe, D, Milanini-Mongiat, J, Pages G, O’Rourke,, DM, Bernhard, E, Maity, A  Akt activation can upregulate VEGF expression independently of hypoxia inducible factor-1 via phosphorylation of Sp1 family members. Mol. Biol. Cell. 15: 4841, 2004.   
• Pore N, Jiang Z, Gupta A, Cerniglia G, Kao GD, Maity A. EGFR tyrosine kinase inhibitors decrease vascular endothelial growth factor (VEGF) expression by both hypoxia inducible factor (HIF)-1 independent and dependent mechanisms. Cancer Res. 66: 3197, 2006.

Randall N. Pittman, Ph.D.

Functional interactions of ataxin-3 with proteins regulating DNA repair and the ubiquitin proteasome system;  Role of ataxin-3 in the ubiquitin proteasome system;   Interactions between  ataxin-3 and Rad23.

• Burnett, B.G. and Pittman, R.N. The polyglutamine neurodegenerative protein ataxin 3 regulates aggresome formation. Proc. Natl. Acad. Sci. USA 102:4330-4335, 2005.
• Burnett, B., Li, F., and Pittman, R.N. The polyglutamine neurodegenerative protein ataxin-3 binds polyubiquitylated proteins and has ubiquitin protease activity. Hum. Mol. Genet., 12:3195-3205, 2003.

Thomas Stamato, Ph.D

• Biaglow JE, Ayene IS, Koch CJ, Donahue J, Stamato TD, Mieyal JJ, Tuttle SW. (2003) Radiation response of cells during altered protein thiol redox.  Radiat Res.159(4):484-94.
•  Ayene IS, Stamato TD, Mauldin SK, Biaglow JE, Tuttle SW, Jenkins SF, Koch CJ. 2002 Mutation in the glucose-6-phosphate dehydrogenase gene leads to inactivation of Ku DNA end binding during oxidative stress. J Biol Chem. 277(12):9929-35.