Harold H. Hines, Jr., Professor
Chair, Department of Radiation and
The Cancer Research Center
Committee on Cancer Biology
Committee on Molecular Medicine/MPMM
M.D., The University of Chicago, 1971
B.S., The University of Wisconsin, Madison
Phone: (773) 702-0187
The University of Chicago
CAM1338, (MC 9006)
5758 South Maryland Avenue
Chicago, Illinois 60637
Related Research Interests:
Ralph Weichselbaum, M.D.
Signal Transduction Pathways Following Exposure to
Ionizing Radiation; Gene Therapy
Our laboratory is studying 1) signal transduction
pathways following exposure of mammalian cells to ionizing radiation
and 2) gene therapy in the treatment of neoplastic disease. Recent
studies have suggested that radiation exposure is associated with the
expression of the c-jun/fos, Egr, and NF-kB gene families. We proposed
that the activation of transcription factors is important in
transduction of early signals to the expression of late genes which
result in the biological response to x-ray-induced damage. Egr-1 and
c-jun induction are central to tumor promotion, proliferation, and
cycle of radiation and are activated by DNA-damaging agents in
mammalian cells. We have defined the DNA elements and mechanisms
responsible for radiation activation of Egr-1 and jun. We have extended
our work to examine cytoplasmic signaling cascades that induce
radiation-induced signals to the nucleus, including MAP kinase, the
ribosomal protein S6 kinase pp90rsk, and p56/p53lyn. Gene therapy is
generally not well localized. We proposed that ionizing radiation could
be used to activate the transcription of exogenous genes that encodes
cytotoxic or radioprotective proteins. To test this model, we have
generated a vector expressing TNF-alpha under the control of the
radiation-responsive Egr-1 promoter. When this construct was used in an
experimental animal system, we observed an increase in tumor cures
without an increase in normal tissue toxicity.
Hallahan DE, Virudachalam S, Kuchibhotla J, Kufe DW,
Weichselbaum RR. (1994). Membrane-derived second messenger regulates
x-ray-mediated TNF-alpha gene induction. Proc Natl Acad Sci USA,
Kharbanda S, Saleem A, Shafman T, Emoto Y, Weichselbaum
RR, Kufe DW. (1994). Activation of the pp90rsk and mitogen-activated
serine/threonine protein kinases by ionizing radiation. Proc Natl Acad
Sci USA, 91:5416-5420.
Weichselbaum RR, Hallahan DE, Beckett MA, Mauceri J, Lee
H, Sukhatme VP, Kufe DW. (1994). Gene therapy targeted by radiation
preferentially radiosensitizes tumor cells. Cancer Res, 54:4266-4269.
Haraf DJ, Rubin SJ, Sweeney P, Kuchnir FT, Sutton HG,
Chodak GW, and Weichselbaum RR. (1995). Photon Neutron
Mixed-Beam Radiotherapy of Locally Advanced Prostate Cancer.
Journal of Radiation Oncology, Biology, Physics 33:3-14.
Vokes EE, Stupp R, Haraf D, Moran W, Malone D, Wenig B,
Sweeney P, and Weichselbaum RR. (1995).
Hydroxyurea with Continuous Infusion Paclitaxel, 5-Fluorouracil, and
Concomitant Radiotherapy for Poor-Prognosis Head and Neck Cancer.
of Oncology 22: 47-52.
Vokes EE, Haraf DJ, Stenson K, Stupp R, Malone D, Levin
J, Weichselbaum RR. (1995). The Role of Paclitaxel in the
Treatment of Head and Neck Cancer. Seminar of Oncology 22:
Krishnasamy S, Vokes EE, Dohrmann GJ, Mick R, Garcia
JC, Kolker JD, Wollman RL, Hekmatpanah J, and Weichselbaum, RR. (1995).
Concomitant Chemoradiotherapy, Neutron Boost, and Adjuvant Chemotherapy
for Anaplastic Astrocytoma and Glioblastoma Multiforme. Cancer
Investigations 13: 453-459.
Heimann R, Powers C, Halpern HJ, Michel AG, Ewing CA,
Wyman B, Recant W, Weichselbaum RR. (1996). Breast
Preservation in Stage I and II Carcinoma of the Breast. Cancer
Datta R, Kojima H, Banach D, Bump NJ, Talanian RV,
Alnemri E, Weichselbaum RR, Wong WW, Kufe
D. (1996). Activation of a Crm-A-insensitive, p35-sensitive Pathway in
Radiation-induced Apoptosis: Journal of Biological Chemistry
Haraf DJ, Weichselbaum RR,
Vokes EE. (1996). Re-irradiation with Concomitant Chemotherapy of
Recurrent Head and Neck Cancer: A Potentially Curable Disease.
Vijayakumar S, Vaida F, Weichselbaum RR,
Hellman S. (1997). Race and the Will Rogers Phenomenon in Prostate
Cancer Journal, IV: 27-34,1997.
Vokes EE, Liebowitz DN, Weichselbaum RR. (1997).
Nasopharyngeal Carcinoma, Lancet 350: 1087-91.
Mundt AJ, Weichselbaum RR. (1997). Tumors of
The Soft Tissue, 2nd Edition, DasGupta TK, Chaudhuri PK, (eds.),
Appleton & Lange (publs.), Stanford, CT. Radiation Therapy of Soft
Tissue Tumors Chapter 17.
Yuan ZM, Utsugisawa T, Huang Y, Ishiko T, Nakada S,
Kharbanda S, Weichselbaum RR, Kufe D. (1997). Inhibition of
PI 3-kinase by c-Abl in the genotoxic stress response. Journal of
Biological Chemistry 272: 23485-23488.
Chung TDK, Mauceri HJ, Hallahan DE, Yu JJ, Chung S,
Grdina WL, Yajnik S, Weichselbaum R. R., Kufe DW. (1998).
"Tumor necrosis factor- based gene therapy enhances radiation
cytotoxicity in human prostate cancer." Cancer Gene Therapy, V
Yuan ZM, Kharbanda S, Kufe D. (1998). "Involvement of
tyrosine kinase in the apoptotic response to anti-cancer agents."
J and Dive C, eds. Cancer Chemotherapy and Apoptosis. Humana Press.
Mauceri HJ, Salloum RM, Gately S, Hellman S, Beckett
MA, Sukhatme VP, Soff GA, Kufe D.W.and Weichselbaum R. R.
(1998). "Potentiation of the Anti-tumor Effect of Ionizing Radiation by
Concomitant Exposures to Angiostatin." Cancer Research, 58
Kies MS, Haraf DF, Athanasiadis I, Kozloff M, Mittal B,
Pelzer H, Rademaker AW, Wenig B, Vokes EE, Weichselbaum RR.
(1998). "Induction chemotherapy followed by concurrent chemoradiation
advanced head and neck cancer: improved disease control and survival."
of Clinical Oncology, 16 #8 2715-2721.
Kumar S, Pandey P, Bharti A, Jin S, Weichselbaum
RR, Weaver D, Kufe D, Kharbanda S. (1998). "Regulation of
DNA-dependent protein kinase by the Lyn tyrosine kinase." Journal
of Biological Chemistry, 273 25654-58.
Mauceri HJ, Nanna NN, Staba MJ, Beckett MA, Kufe DK and
Weichselbaum RR. (1999). "Radiation-Inducible
genetherapy." C.R. Acad. Sci. Paris, Sciences de la vie/Life
Sciences, 322 225-228.
Hannig J, Yu J, Beckett M, Weichselbaum RR and
Lee RC. (1999). Poloxamine 1107 sealing of radiopermeabilized
membranes." Int. J. Radiat. Biol. 75 3, 379-385.
Gorski DH, Mauceri HJ, Salloum RM, Gately S, Hellman,
S, Beckett MA, Sukhatme VP, Soff GA, Kufe DW, Weichselbaum RR. (1999).
"Potentiation of the antitumor effect of ionizing radiation
by brief concomitant exposures to angiostatin." Cancer Research 58
Vokes EE, Haraf DJ, Brockstein E, Weichselbaum
RR. (1999). "Paclitaxel, 5-Fluorouracil, Hydroxyurea, and
Concomitant Radiation Therapy for Poor-Prognosis Head and Neck Cancer."
Seminars in Radiation Oncology, 9, 2, Suppl 1 70-76.
Faculty and Research