Download PHS 398 (Rev. 9/04), Biographical Sketch Format Page

Principal Investigator/Program Director (Last, First, Middle):
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
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NAME
POSITION TITLE
Brown, J. Martin
Professor
eRA COMMONS USER NAME
MARTIN.BROWN
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
YEAR(s)
FIELD OF STUDY
Birmingham University, UK
BS
1963
Physics
Radiation Physics &
London University, UK
MS
1965
Radiation
Biology
Oxford University, UK
PHD
1968
Cancer
Biology
A. Positions and Honors.
Positions Held:
Stanford University, Dept. Radiation Oncology 1968–present
Post-doctoral Fellow, l968–70
Research Associate, l970–7l
Assistant Professor, l97l–77
Associate Professor, l977–84
Professor, 1984–
Director, Division of Radiation and Cancer Biology, 1984–2003
Director, Program in Cancer Biology, 1990–2002
Honors and Awards:
Ninth Radiation Research Society Research Award, l980.
Henry S. Kaplan Memorial Teaching Award, 1989.
Radiation Study Section, 1992–96 (Chair, 1994–96)
Science Council RERF 1997-2002 (Chair 99-02).
AACR Bruce Cain Memorial Awardee, 1999.
ASTRO Gold Medal, 1999.
1st Int Conf on Translational Research, G.E. Adams Award, 2000.
Failla Award, Radiation Res Soc, 2000.
Weiss Medal, Assoc Radiation Res, 2001
Honorary member of the European Society for Therapeutic Radiology & Oncology
Henry S. Kaplan Distinguished Scientist Award, International Association of
Radiation Research, 2007
Current Associate Editor of Anticancer Research, Radiotherapy &
Oncology, Neoplasia, Cancer Letters, Molecular Cancer Therapeutics and Cancer
Biology & Therapy. Senior Editor for Biology International J Radiation Oncology,
Biology Physics.
B. Selected peer-reviewed publications from past 10 years (from total of 295).
Liu, S.C., Minton, N.P., Giaccia, A.J., and Brown, J.M. (2002) Anticancer efficacy of systemically delivered
anaerobic bacteria as gene therapy vectors targeting tumor hypoxia/necrosis. Gene Ther. 9: 291–296.
Birrell, G.W., Brown, J.A., Wu, I., Giaever, G., Chu, A.M., Davis, R.W., and Brown, J.M. (2002) Transcriptional
response of Saccharomyces cerevisiae to DNA-damaging agents does not identify the genes that protect
against these agents. PNAS 99(13): 8778–8783.
Peters, K.B. and Brown, J.M. (2002) Tirapazamine: A hypoxia-activated topoisomerase II poison. Cancer
Res. 62: 5248–5253.
Chen, G.K., Lacayo, N.J., Durán, G.E., Wang, Y., Bangs, C.D., Rea, S., Kovacs, M., Cherry, A.M., Brown,
J.M., and Sikic, B.I. (2002) Preferential expression of a mutant allele of the amplified ABCB1 gene in drugresistant variants of a human sarcoma. Genes Chromosomes Cancer 34: 372–383.
Vordermark, D., Menke, D.R., and Brown, J.M. (2003) Similar Radiation Sensitivities of Acutely and
Chronically Hypoxic Cells in HT 1080 Fibrosarcoma Xenografts. Radiat. Res. 159: 94–101.
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Principal Investigator/Program Director (Last, First, Middle):
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Game, J.C., Birrell, G.W., Brown, J.A., Shibata, T., Baccari, C., Chu, A.M., Williamson, M.S., and Brown, J.M.
(2003) Use of a genome-wide approach to identify new genes that control resistance to Saccharomyces
cerevisiae to ionizing radiation. Radiat. Res. 160: 14–24.
Delahoussaye, Y.M., Hay, M.P., Pruijn, F.B., Denny, W.A., and Brown, J.M. (2003) Improved potency of the
hypoxic cytotoxin tirapazamine by DNA-targeting. Biochem. Pharmacol. 65(11): 1807–1815.
Brown, J.M. and Wilson, G. (2003) Apoptosis genes and resistance to cancer therapy: what do the
experimental and clinical data tell us? Cancer Biol. Ther. 2(5): 477–490.
Brown, J.M. and Wilson, W. (2004) Exploiting tumour hypoxia in cancer treatment. Nat. Rev. Cancer 2(5):
437–447.
Wu, H.I., Brown, ,J.A., Dorie, M.J., Lazzeroni, L. and Brown, J.M. (2004) Genome-wide identification of genes
conferring resistance to the anticancer agents cisplatin, oxaliplatin and mitomycin C. Cancer Res. 64:
3940–3948.
Haugen, A.C., Kelley, R., Collins, J.B., Tucker, C.J., Deng, C., Afshari, C.A., Brown, J.M., Ideker, T., and Van
Houten, B. (2004) Integrating phenotypic and expression profiles to map arsenic-response networks.
Genome Biol. 5(12): R95.
Brown, J.M. and Attardi, L.D. (2005) The role of apoptosis in cancer development and treatment response.
Nat. Rev. Cancer 5(3): 231–237.
Deng, C., Brown, J.A., You, D, and Brown, J.M. (2005) Multiple Endonucleases Function to Repair Covalent
Topoisomerase I Complexes in S. cerevisiae. Genetics 170(2):591-600
Chen Y, Feldman D.E, Deng C, Brown J.A, De Giacomo A.F, Gaw A.F, Shi G, Le Q.T, Brown J.M, Koong A.C
(2005) Identification of mitogen-activated protein kinase signaling pathways that confer resistance to
endoplasmic reticulum stress in Saccharomyces cerevisiae. Mol Cancer Res. 12:669-677.
Brown, J.A., Sherlock, G., Myers, C.L., Burrows, N.M., Deng, C., Wu, H.I., McCann, K.E., Troyanskaya, O.G.,
and Brown, J.M. (2006) Global analysis of gene function in yeast by quantitative phenotypic profiling. Mol
Syst Biol, (Epub Jan 17)
Game, J.C, Marsha S. Williamson, M.S., Spicakova, T. and Brown, J.M. (2006): The RAD6/BRE1 histone
modification pathway in Saccharomyces confers radiation resistance through a RAD51-dependent
process that is independent of RAD18. Genetics 173: 1951-168.
Hicks, K.O., Pruijn, F.B., Secomb, T.W., Hay, M.P., Hsu, R., Brown, J.M., Denny, W.A., Dewhirst, M.W.,
and Wilson, W.R. (2006) Penetration of three dimensional tissue cultures predicts in vivo activity of
hypoxia-targeted anticancer drugs. J. Nat. Cancer Instit ;98:1118-28
Ahn, G-O, and Brown, M. (2007) Targeting tumors with hypoxia-activated cytotoxins. Frontiers in
Bioscience 12: 3483-3501
Evans J.W., Chernikova, S.B., Kachnic, L.A., Banath, J.P., Sordet O., Delahoussaye, Y.M., Treszezamsky,
A., Chon, B.H., Feng, Z., Gu Y., Wilson, Wi.R., Pommier, Y., Olive, P.L., Powell, S.N., and Brown J. M.
(2007) Homologous Recombination is the Principal Pathway for the Repair of DNA Damage induced by
Tirapazamine in Mammalian Cells. Cancer Res 68: 257-265
Ahn, G-O, and Brown, M. (2008) Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for
angiogenesis: Role of bone marrow-derived myelomonocytic cells, Cancer Cell 13: 193-205.
Liu, S-C, Ahn, G-O, Kioi, M, Dorie, M.J, Patterson A.V. and Brown, J.M. (2008) Optimized ClostridiaDirected Enzyme Prodrug Therapy Improves the Antitumor Activity of the Novel DNA-Cross-Linking
Agent PR-104, Cancer Res 68:7995-8003.
Spicakova, T., McCann. K. and Brown, J.M. (2008) A Role for Lsm1p in Response to Ultraviolet Radiation
Damage in Saccharomyces cerevisiae Rad Res 170: 411-421.
Song S, McCann KE, Brown JM.( 2008) Radiosensitization of yeast cells by inhibition of histone h4
acetylation. Radiat Res. 170(5):618-27
Ahn G-O and Brown J.M. (2009) Role of endothelial progenitors and other bone marrow-derived cells in the
development of the tumor vasculature. Angiogenesis 12(2):159-64.
Diehn M., Cho R.W., Lobo N.A., Kalisky T., Dorie M.J, Kulp A.N., Qian D., Lam J.S., Ailles L.E., Wong M,
Joshua B, Kaplan M.J., Wapnir I, Dirbas F, Somlo G, Garberoglio C., Paz B., Shen J., Lau S.K., Quake
S.R., Brown J.M., Weissman I.L., Clarke M.F. (2009) Association of reactive oxygen species levels and
radioresistance in cancer stem cells. Nature Feb 4, PMID: 19194462
Ahn,G-O., and Brown, J.M. (2009) Influence of bone marrow-derived hematopoietic cells on the tumor
response to radiotherapy: Experimental models and clinical perspectives. Cell Cycle Apr 1;8(7):970-6.
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Principal Investigator/Program Director (Last, First, Middle):
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Gu Y, Patterson AV, Atwell GJ, Chernikova SB, Brown JM, Thompson LH, Wilson WR. (2009) Roles of
DNA repair and reductase activity in the cytotoxicity of the hypoxia-activated dinitrobenzamide mustard
PR-104A. Mol Cancer Ther.;8(6):1714-23
Singleton,RS Guise, CP, Ferry, DM Pullen, SM, Dorie, MJ, Brown, JM, Patterson, AV, Wilson WR.(2009)
DNA crosslinks in human tumor cells exposed to the prodrug PR-104A: relationships to hypoxia,
bioreductive metabolism and cytotoxicity Cancer Res 69:3884-91
Coffelt, SB, Lewis, CE, Naldini, L, Brown, JM, Ferrara, N, De Palma M (2010) Elusive Identities and
Overlapping Phenotypes of Proangiogenic Myeloid Cells in Tumors. American J Pathology 176:1564-76
Kioi, M, Vogel, H, Schultz, G., Hoffman, RM., Harsh, GR., Brown, JM (2010) Inhibition of vasculogenesis, but
not angiogenesis, prevents the recurrence of glioblastoma following irradiation in mice. J Clin Invest
120:694-705.
Ahn, GO Tseng, D, Liao, CH, Dorie, MJ. Czechowicz, A. Brown, JM (2010) Inhibition of Mac-1 (CD11b/CD18)
enhances tumor response to radiation by reducing myeloid cell recruitment. PNAS 107(18):8363-8,
Brown, JM (2010) The remarkable yin and yang of tumour hypoxia. Int J. Radiat. Biol 2010 Nov;86(11):907-17.
Chernikova SB, Dorth JA, Razorenova OV, Game JC, Brown JM. (2010) Deficiency in Bre1 Impairs
Homologous Recombination Repair and Cell Cycle Checkpoint Response to Radiation Damage in
Mammalian Cells. Radiat Res. 174(5):558-65
Brown JM, Diehn M, Loo BW Jr. (2010( Stereotactic ablative radiotherapy should be combined with a hypoxic
cell radiosensitizer. Int J Radiat Oncol Biol Phys. Oct 1;78(2):323-7.
Carlson DJ, Keall PJ, Loo BW Jr, Chen ZJ, Brown JM. (2011) Hypofractionation results in reduced tumor cell
kill compared to conventional fractionation for tumors with regions of hypoxia. Int J Radiat Oncol Biol Phys.
Mar 15;79(4):1188-95.
Mayes P, Dolloff, N Daniel C, Liu J, Hart L, Kuribayashi K, Allen J, Jee, D Dorsey J, Liu Y, Dicker D, Brown
JM, Furth E, Klein P , Sears R El-Deiry W (2011) Overcoming hypoxia-induced apoptotic resistance
through combinatorial inhibition of GSK-3 and CDK1. Cancer Res 71(15):5265-75
Tseng D, Vasquez-Medrano DA, Brown JM. (2011) Targeting SDF-1/CXCR4 to inhibit tumour vasculature for
treatment of glioblastomas. Br J Cancer. Jun 7;104(12):1805-9.
Chernikova, SB, Game, JC Brown, JM (2012). Inhibiting homologous recombination for cancer therapy,
Cancer Biology and Therapy, 13:2 1-8
Brown JM. (2012) Imaging Tumor Sensitivity to a Bioreductive Prodrug: Two for the Price of One! Clin Cancer
Res.;18(6):1487-9.
Chernikova SB, Razorenova OV, Higgins JP, Sishc BJ, Nicolau M, Dorth JA, Chernikova DA, Kwok S, Brooks
JD, Bailey SM, Game JC, Brown JM (2012) Deficiency in Mammalian Histone H2B Ubiquitin Ligase Bre1
(Rnf20/Rnf40) Leads to Replication Stress and Chromosomal Instability. Cancer Res.72(8):2111-9.
C. Research Support.
Ongoing Research Support
1 R01 CA128873 Brown (PI)
07/01/08- 05/31/13
NIH/NCI
Effect of Bone Marrow Cells on the Radiosensitivity of Brain and Mouth Cancers
Role: PI
The goal of this project is to determine whether the radiosensitivity of brain and head and neck cancers can
be increased by inhibition of vasculogenesis from bone marrow derived cells.
1R01 CA149318 Brown (PI)
08/01/11- 05/31/16
“Development of Clinical Strategies to Prevent GBM Recurrences After Radiotherapy”
Role: PI
The goal of this project is to test various strategies in preclinical models of inhibiting vasculogenesis to improve the
cure rate of glioblastomas
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BROWN, J. Martin
Genzyme Corporation Brown (PI)
07/01/10- 06/01/12
“Investigation of Biomarkers and Timing of Plerixafor Administration after Local Irradiation of GBM in Mice for
Optimum Tumor Response”
Role: PI
The goal is to determine the optimum time for administration of plerixafor in relation to SDF-1 plasma levels
for control of intracranial GBM in the mouse by irradiation.
Completed Research Support
5 P01 CA-067166 Giaccia (PI)
02/09/07-01/31/12
NIH/NCI
Tumor Hypoxia: Molecular Studies & Clinical Exploitation
The major goals of this project are to investigate the molecular, cellular, and clinical implications of tumor
hypoxia, to understand the mechanism of the activity of the hypoxic toxin tirapazamine and to discover new
proteins that can be used to predict the level of tumor hypoxia in cancer patients.
Role: Project Leader
1 R01 CA-118202 Brown (PI)
07/01/06-05/31/11
NIH/NCI
Experimental Radiotherapy and Chemotherapy with a Potent New Hypoxic Cytotoxin
The goal of this project is to investigate the mechanism and clinical potential of a new hypoxic cytotoxin PR104
Role: PI
2 P01 CA-082566 Brown (PI)
04/01/04–03/31/09
NIH/NCI
Development of New Hypoxic Cytotoxins for Cancer Therapy
The goals of these projects are to develop optimum second-generation TPZ analogs for use with fractionated
radiation and cisplatin-based chemotherapy, to develop drugs for use with clostridia-directed enzyme prodrug
therapy, and to identify drugs selectively toxic to cells expressing HIF-1.
Role: PI
James S McDonnell Foundation Brown (PI)
09/01/07- 08/31/08
Increasing the Radiocurability of GBM by Inhibition of Tumor Vasculogenesis.
Role: PI
The goal of this project is to demonstrate that the radiosensitivity of experimental GBM can be increased by
inhibition of vasculogenesis from bone marrow derived cells.
1 R01 GM-073879 Brown (PI)
08/01/05-07/31/08
NIH/NIGMS
Yeast Gene Ontology by Phenotypic Profiling
The goal of this project is to perform functional profiling with the yeast deletion pool to determine the function
of genes whose function is unknown.
Role: PI
W81XWH-04-1-0451 Brown (PI)
04/05/04–04/04/07
Dept of Defense/Army, Breast Cancer Research Program
A Novel Yeast Genomics Method for Identifying New Breast Cancer Susceptibility Genes.
This project employs a new reporter construct to identify yeast genes that lead to genomic instability.
Role: PI
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Principal Investigator/Program Director (Last, First, Middle):
BROWN, J. Martin
Accelerate Brain Cancer Cure Brown (PI)
09/01/06–08/31/07
Sensitization of Brain Tumors to Radiotherapy by Depletion of Bone Marrow Derived Cells
The goal of this project is to identify the bone marrow derived cells that are responsible for the protection of
brain-implanted gliomas to irradiation and to target these cells or their growth factor products in combination
with fractionated local tumor irradiation.
Role: PI
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