Joe Gray

faculty photo

Email:
Phone: 503 494-6500
Curriculum Vitae

Current Appointments
Professor and Gordon Moore Endowed Chair, Department of Biomedical Engineering
Director, OHSU Center for Spatial Systems Biomedicine
Associate Director for Biophysical Oncology, Knight Cancer Institute

Office
Collaborative Life Sciences Building
Mail Code: CL3G
2730 SW Moody Ave., Room #3N026
Portland, OR 97201-5042

Dr. Joe W. Gray, a physicist and an engineer by training, holds positions as Professor and Gordon Moore Endowed Chair, Biomedical Engineering Department Vice Chair; Director, Center for Spatial Systems Biomedicine (OCSSB); and Associate Director for Biophysical Oncology, Knight Cancer Institute at the Oregon Health & Science University. He is also Emeritus Professor, University of California, San Francisco; and Senior Scientist, Lawrence Berkeley National Laboratory. He was a Staff Scientist in the Biomedical Sciences Division of the Lawrence Livermore National Laboratory (1972-1991), Professor of Laboratory Medicine at the University of California, San Francisco (1991-2011), and Associate Laboratory Director for Biosciences and Life Sciences Division Director at the Lawrence Berkeley National Laboratory (2003-2011). He is Principal Investigator of the National Cancer Institute / Research Center for Cancer Systems Biology Consortium (CSBC), "Measuring, Modeling and Controlling Heterogeneity" (M2CH) that is aimed at developing a systems level understanding of how intrinsic and extrinsic factors work together to enable triple-negative breast cancer to escape therapeutic control in order to devise robust control strategies; PI of a National Institutes of Health program to contribute to further development of the NIH Library of Integrated Network-based Cellular Signatures program (LINCS) to develop a dataset and computational strategy to elucidate how microenvironmental signals affect cell intrinsic intracellular transcriptional- and protein-defined molecular networks to generate experimentally durable therapies for patients; PI of a Prospect Creek Foundation study "Serial Measurement of Molecular and Architectural Responses to Therapy" (SMMART) to provide a transformative approach to cancer treatment that focuses on each person who faces cancer to create more effective, durable therapies for treatment of prostate cancer, pancreatic cancer and leukemia; PI of a Brenden Colson Center for Pancreatic Health that provides support for a broad-based, team approach to finding causes, early detection and improvement of clinical care for pancreatic diseases including pancreatitis and pancreatic cancer; and PI of a Susan G. Komen project to identify the mechanisms by which ERBB2+ breast cancer cells escape inhibition by ERRB2-targeted therapies.

Dr. Gray's work is described in over 400 publications and in 80 US patents. He is a Fellow of the American Association for the Advancement of Science and the American Institute for Medical and Biological Engineering; an elected a member of the Institute of Medicine of the National Academy of Sciences; a member of the National Institutes of Health, Frederick Advisory Committee to the Director of the National Cancer Institute; a Fellow of the American Association of Cancer Research Academy; and United States Councilor to the Radiation Effects Research Foundation (RERF), Hiroshima, Japan

Professional Associations
Dr. Gray is involved in several projects and collaborations with organizations outside of Oregon Health & Science University.

Research Interests
The Gray Laboratory explores mechanisms by which genomic, transcriptional and proteomic abnormalities occur in selected cancers, elucidates how these abnormalities contribute to cancer pathophysiologies and assesses the ways in which these abnormalities influence responses to gene targeted therapies. Current studies focus on developing: (a) integrated analyses of the spectrum of recurrent abnormalities that influence cancer behavior (b) mathematical models that describe how cancer-associated molecular abnormalities influence individual responses to therapeutic inhibitors (c) novel therapeutic approaches to treat breast or ovarian cancer subpopulations that do not respond well to current aggressive chemotherapeutic strategies (d) proteomic strategies for early detection of breast cancer related proteins in blood (e) automated functional assessment of genes deregulated by genomic abnormalities in cancers, and (f) molecular imaging for early detection of metastasis prone breast cancer.

Integrated analysis
We are assessing abnormalities associated with clinical outcome in breast cancers using a combination of comparative genomic hybridization (CGH), massively parallel sequencing (whole exome sequencing and RNA sequencing) and reverse phase protein lysate arrays to assess allele specific genome copy number, RNA expression, and protein and phosphoprotein levels in cancer related genes. These studies are supported by the NCI Bay Area Breast Cancer SPORE and The Cancer Genome Altas project.

Mathematical models
We are developing mathematical methods to predict individual responses to therapeutic agents using information on responses to these agents in a collection of cell lines grown in vitro. Major emphasis in this project is on breast cancer. Current emphasis is on development of statistical, Bayesian and ODE models of Her-family signaling. Work in this area is supported by an NCI Center for Cancer Systems Biology award.

Novel therapeutic approaches
We are using advanced genomic analysis and high content, high throughput imaging to assess responses to NCI and private sector compounds for our collection of ~100 breast, ovary, prostate and pancreas cancer cell lines. Our goal is to identify therapeutic agents that will be highly effective against tumor subtypes that do poorly on aggressive therapy. In addition, we are developing siRNA therapeutic approaches to treat tumors that amplify and overexpress transcripts to which the tumors become addicted. Current emphasis is on development of strategies to identify and inhibit functionally important genes in regions of amplification associated with poor outcome. This work is supported by an NCI Ovarian Cancer Specialized Program of Research Excellence (SPORE),the NCI Bay Area Breast Cancer SPORE, and the NIH Foundation.

Early detection
We are using information about genomic and transcriptional abnormalities in breast cancer to guide the development of mass spectrometric strategies that can detect breast cancer subtype specific proteins in order to enable early detection of metastasis prone breast cancers. We are giving special attention to detection of aberrant proteins that result from cancer specific alternative splicing, glycosylation or phosphorylation. Mass spectrometry and capillary isoelectric focusing approaches are being developed to detect these proteins in the blood, MRI and PET imaging approaches are being developed for anatomic detection and scanned ion beam mass spectrometry is being developed for improved histopathological analysis. These studies are supported by  a grant from the NCI Clinical Proteomic Technologies for Cancer (CPTAC) program.

Recent Publications

Hu, Z., Mao, J.H., Curtis, C., Huang, G., Gu, S., Heiser, L., Lenburg, M.E., Korkola, J.E., Bayani, N., Samarajiwa, S., Seoane, JA, Dane M.A., Esch, A., Feiler, H.S., Wang, N.J., Hardwicke, M.A., Laquerre, S., Jackson, J., Wood, K.W., Weber, B., Spellman, P.T., Aparicio, S., Wooster, R., Caldas, C., Gray, J.W. (2016) Genome co-amplification upregulates a mitotic gene network activity that predicts outcome and response to mitotic protein inhibitors in breast cancer Breast Cancer Res. 18(1):70. PMC4930593

Guest, S.T., Kratche, Z.R., Irish, J.C., Wilson, R.C., Haddad, R., Gray, J.W., Garrett-Mayer, E., Ethier, S.P. (2016) Functional oncogene signatures guide rationally designed combination therapies to synergistically induce breast cancer cell death. Oncotarget. 7(24):36138-36153. PMID: 27153554

Ngamcherdtrakul, W.,Castro, D.J., Gu, S., Morry, J., Reda, M., Gray, J.W., Yantasee, W. (2016)Current development of targeted oligonucleotide-based cancer therapies:Perspective on HER2 positive breast cancer treatment. Cancer Treat Rev.45:19-29. PMC4826844

Hill, S.M., Heiser, L.M., Cokelaer, T., Unger, M., Nesser, N.K., Carlin, D.E., Zhang, Y., Sokolov, A., Paull, E.O., Wong, C.K., Graim, K., Bivol, A., Wang, H., Zhu, F., Afsari, B., Danilova, L.V., Favorov, A.V., Lee, W.S., Taylor, D., Hu, C.W., Long, B.L., Noren, D.P., Bisberg, A.J.; HPN-DREAM Consortium, Mills, G.B., Gray, J.W., Kellen, M., Norman, T., Friend, S., Qutub, A.A., Fertig, E.J., Guan, Y., Song, M., Stuart, J.M., Spellman, P.T., Koeppl, H., Stolovitzky, G., Saez-Rodriguez, J., Mukherjee, S. (2016) Inferring causal molecular networks: empirical assessment through a community-based effort. Nat. Methods. (4):310-8. PMC4854847

Gu S, Hu Z, Ngamcherdtrakul W, Castro DJ, Morry J, Reda MM, Gray JW, Yantasee W. (2016) Therapeutic siRNA for drug-resistant HER2-positive breast cancer. Oncotarget. 7(12):14727-41. PMC4924747

Shain, A.H., Garrido, M., Botton, T., Talevich, E., Yeh, I., Sanborn, J.Z., Chung, J.,Wang, N.J., Kakavand, H., Mann, G.J., Thompson, J.F., Wiesner, T., Roy, R., Olshen, A.B., Gagnon, A., Gray, J.W., Huh, N., Hur, J.S., Busam, K.J., Scolyer, R.A., Cho, R.J., Murali, R., Bastian, B.C. (2015) Exome sequencing of desmoplastic melanoma identifies recurrent NFKBIE promoter mutations and diverse activating mutations in the MAPK pathway. Nat Genet., 47(10):1194-9. PMC4589486

Gray, J.W., and Mills, G.B. (2015) Large-scale drug screens support precision medicine. Cancer Discov. 5(11):1130-2. PMC4633700

Butler, T.M., Johnson-Camacho, K., Peto, M., Wang, N.J., Macey, T.A., Korkola, J.E., Koppie, T.M., Corless, C.L., Gray, J.W., Spellman, P.T. (2015) Exome sequencing of cell-free DNA from metastatic cancer patients identifies clinically actionable mutations distinct from primary disease.  PLoS One, 10(8):e0136407. PMC4552879

Sanborn, J.Z., Chung, J., Purdom, E., Wang, N.J., Kakavand, H., Wilmott, J.S., Butler, T., Thompson, J.F., Mann, G.J., Haydu, L.E., Saw, R.P., Busam, K.J., Lo, R.S., Collisson, E.A., Hur, J.S., Spellman, P.T., Cleaver, J.E., Gray, J.W., Huh, N., Murali, R., Scolyer, R.A., Bastian, B.C., Cho, R.J. (2015) Phylogenetic analyses of melanoma reveal complex patterns of metastatic dissemination. Proc. Natl. Acad. Sci. USA, 112(35):10995-1000. PMC4568214

Goodspeed, A., Heiser, L.M., Gray, J.W., Costello, J.C. (2016) Tumor-derived cell lines as molecular models of cancer pharmacogenomics. Mol. Cancer Res., 14(1):3-13. PMC4828339

Korkola, J.E., Collisson, E.A., Heiser, L., Oates, C., Bayani, N., Itani, S., Esch, A., Thompson, W., Griffith, O.L., Wang, N.J., Kuo, W.L., Cooper, B., Billig, J., Ziyad, S., Hung, J.L., Jakkula, L., Feiler, H., Lu, Y., Mills, G.B., Spellman, P.T., Tomlin, C., Mukherjee, S., Gray, J.W. (2015) Decoupling of the P13K pathway via mutation necessitates combinatorial treatment in HER2+ breast cancer. PLoS One, 10(7):e0133219. PMC4504492

Ngamcherdtrakul, W., Morry, J., Gu, S., Castro, D.J., Goodyear, S.M., Sangvanich, T., Reda, M.M., Lee, R., Mihelic, S.A., Beckman, B.L., Hu, Z., Gray, J.W., Yantasee, W. (2015) Cationic polymer modified mesoporous silica nanoparticles for targeted siRNA delivery to HER2+ breast cancer. Adv. Funct. Mater., 25(18):2646-2659. PMC4469082

Nan, X., Tamgüney, T.M., Collisson, E.A., Lin, L.J., Pitt, C., Galeas, J., Lewis, S., Gray, J.W., McCormick, F., Chu, S. (2015) Ras-GTP dimers activate the Mitogen-Activated Protein Kinase (MAPK) pathway. Proc. Natl. Acad. Sci. USA, 112(26):7996-8001. PMC4491781

Giuliano, M., Hu, H., Wang, Y.C., Fu, X., Nardone, A., Herrera, S., Mao, S., Contreras, A., Gutierrez, C., Tao, W., Hilsenbeck, S.G., De Angelis, C., Wang, N.J., Heiser, L., Gray, J.W., Lopez-Tarruella, S., Pavlick, A., Trivedi, M.V., Chamness, G.C., Chang, J.C., Osborne, C.K., Rimawi, M.F., Schiff, R. (2015) Upregulation of ER signaling as an adaptive mechanism of cell survival in HER2-positive breast tumors treated with anti-HER2 therapy. Clin. Cancer Res., 21(17):3995-4003. PMC4558260

Daemen, A., Griffith, O.L., Heiser, L.M., Wang, N.J., Enache, O.M., Sanborn, Z., Pepin, F., Durinck, S., Korkola, J.E., Griffith, M., Hur, J.S., Huh, N., Chung, J., Cope, L., Fackler, M.J., Umbricht, C., Sukumar, S., Seth, P., Sukhatme, V.P., Jakkula, L.R., Lu, Y., Mills, G.B., Cho, R.J., Collisson, E.A., van 't Veer, L.J., Spellman, P.T., Gray, J.W. (2015) Erratum to: Modeling precision treatment of breast cancer. Genome Biol., 16(1):95. PMC4426644

Issued United States Patents

Finding leaks in a tandem Van de Graff accelerator

  • Gray, J.W., Hartnell, G.W., and Legg, J.C. Method of locating defects in a high-voltage insulating tube. U.S. Patent #3,76l,720 (1974)
Flow cytometry and sorting
  • Gray, J.W., Alger, T.W., and Lord, D. Fluidic assembly for an ultra-high-speed chromosome flow sorter. U.S. Patent #4,361,400 (1982)
  • Gray, J.W., Hirschfeld, T.B., and Norgren, R.M. Method and apparatus for fringe-scanning chromosome analysis. U.S. Patent #4,596,036 (1986)
BrdUrd/DNA analysis
  • Dolbeare, F. and Gray, J.W. Flow cytometric measurement of total DNA and incorporated halodeoxyuridine. U.S. Patents #4,585,736 (1986); #4,780,406 (1988); #4,812,394 (1989)
Fluorescence in situ hybridization (FISH)
  • Gray, J.W. and Pinkel, D. Methods of preparing and applying single stranded DNA probes to double stranded target DNAs in situ. U.S. Patent #5,028,525 (1991)
  • Gray, J.W. and Pinkel, D. Methods for chromosome-specific staining. U.S. Patents #5,447,841 (1995); #6,596,479 (1995); #6,607,877 (2003); #6,872,817 (2005)
  • Gray, J.W., Pinkel, D., and Tkachuk, D. Method of detecting genetic translocations identified with chromosomal abnormalities (BCR/ABL translocation). U.S. Patent #6,280,929 (2001)
  • Gray, J.W. and Pinkel, D. Methods of biological dosimetry employing chromosome-specific staining. U.S. Patent #6,132,961 (2000)
  • Gray, J.W., Pinkel, D., Kallioniemi, O.-P., Kallioniemi, A., and Sakamoto, M. Methods of staining target chromosomal DNA employing high complexity nucleic acid probes. U.S. Patent #7,115,709 (2006)
  • Pinkel, D., Kallioniemi, O.-P., Kallioniemi, A., Waldman, F., Gray, J.W., and Sakamoto, M. Genomic probing. U.S. Patent #5,856,097 (1995)
  • Weier, H.-U. and Gray, J.W. Repeat sequence chromosome specific nucleic acid probes and methods of preparing and using. U.S. Patent #5,427,932 (1995)
  • Gray, J.W., Stokke, T., and Pinkel, D. Detection of amplified or deleted chromosomal regions. U.S. Patents #5,472,842 (1995); #5,633,365 (1997).
  • Gray, J.W. and Weier, H.-U. Y-Chromosome specific nucleic acid probe and method for determining the y-chromosome in situ. U.S. Patents #5,840,482 (1998); #5,888,730 (1999); #6,300,066 (2001)
  • Gray, J. and Weier, H.-U. Quantitative DNA fiber mapping. U.S. Patent #5,851,769 (1998)
Comparative genomic hybridization (CGH)
  • Pinkel, D., Gray, J.W., Kallioniemi, A., Kallioniemi, O.-P., and Waldman, F. Comparative genomic hybridization (CGH). U.S. Patent #5,665,549 (1997); #5,721,098 (1998); #5,965,362 (1999); #5,976,790 (1999); #6,159,685 (2000); #6,335,167 (2002); #7,238,484 (2007), #7,537,895 (2009)
  • Pinkel, D., Albertson, D., and Gray, J.W. Comparative fluorescence hybridization to nucleic acid arrays. U.S. Patents #5,830,645 (1998); #6,562,565 (2003)
  • Pinkel, D. and Gray, J.W. High density array fabrication and readout method for a fiber optic biosensor. U.S. Patents #5,690,894 (1997); #6,146,593 (2000); #6,417,506 (2002)
  • Pinkel, D., Albertson, D.G., and Gray, J.W. Array-based detection of genetic alterations associated with disease. U.S. Patents #6,210,878 (2001); #7,267,947 (2007)
  • Gray, J.W., Pinkel, D., Albertson, D., Collins, C.C., and Baldocchi, R. Comparative fluorescence hybridization to oligonucleotide microarrays. U.S. Patent #6,465,182 (2002)
  • Pinkel, D., Albertson, D.G., Gray, J.W., Hamilton, G., Brown, N.W., and Clark, S.M. High-efficiency microarray printing device. U.S. Patent #6,855,538 (2005)
  • Albertson, D., Pinkel, D., Fridyland, J., Huey, B., Snijders, A., Gray, J.W., Kallioniemi, A., Kallioniemi, O., Waldman, F. Detection of nucleic acid differences by comparative genomic hybridization. U.S. Patent #7,534,567 (2009)
Diagnostic markers
  • Christman, M.F., Gray, J.W., Levin, N.A., Brzoska, P., and Nakamura, H. Genetic alterations that correlate with lung carcinomas. U.S. Patent #5,670,314 (1997)
  • Gray, J.W., Pinkel, D. Collins, C., Kallioniemi, O.-P., and Tanner, M. Amplification of chromosomal region 20q13 as prognostic indicator in breast cancer. U.S. Patents #5,801,021 (1998); #6,268,184 (2001)
  • Gray, J., Collins, C., Godfrey, T., Kowbel, D., Hwang, S., and Rommens, J. Genes from the 20Q13 amplicon and their uses. U.S. Patents #5,892,010 (1999); # 6,808,878 (2005); # 7,049,424 (2006); # 7,413,899 (2008)
  • Shayesteh, L. and Gray, J.W. Genetic aberrations associated with cancer (PIK3CA). U.S. Patents #6,110,673 (2000); #6,277,563 (2001); #6,475,732 (2002); #6,537,761 (2003); # 7,670,767 (2010)
  • Gray, J.W., Pinkel, D., Kallioniemi, O.-P., Kallioniemi, A., and Sakamoto, M. Chromosome-specific staining to detect genetic rearrangements associated with chromosome 3 and/or chromosome 17. U.S. Patents #6,475,720 (2002); #6,344,315 (2002); #RE40,929 (2009)
  • Gray, J.W., Pinkel, D., Tkachuk, D., and Westbrook, C. Chromosome specific staining to detect genetic rearrangements. U.S. Patent Application #09/765,291 (2001, amendment filed 2007)
  • Gray, J.W. and Pinkel, D. Methods and compositions for chromosome 21-specific staining. U.S. Patent #6,500,612 (2002)
  • Albertson, D.G., Pinkel, D., Collins, C., and Gray, J.W. Amplicon in the 20q13 region of human chromosome 20 and uses thereof. U.S. Patent #6,664,057 (2003)
  • Giacomini, K.M., Gray, J.W., Lapuk, A.V., and Zhang, S. Use of organic cation transporters for cancer diagnosis and therapy. U.S. Provisional Patent Application #60/793,803 (2006)
  • Albertson, D., Pinkel, D., Collins, C., Gray, J.W., Ystra, B. Detecting CYP24 expression level as a marker for predisposition to cancer. U.S. Patent #7,648,826 (2010)
End sequence profiling (ESP)
  • Collins, C., Volik, S., and Gray, J.W. End sequence profiling. U.S. Patent #6,785,614 (2004)
Mass spectrometric imaging of mass tag labeled specimens
  • Felton, James S., Wu, Kuang Jen J., Knize, Mark G., Kulp, Kristen S., Gray, Joe W. Imaging mass spectrometer with mass tags. US Patent #7,728,287 (2010)
Others
  • Ginzinger, D., Godfrey, T., Jensen, R., and Gray, J.W. Quantitative PCR method to enumerate DNA copy number. U.S. Patent #6,180,349 (2001)
  • Fulwyler, M.J. and Gray, J.W. Capillary array and related methods. US Patents #6,610,499 (2003); #6,818,184 (2005); #6,898,237 (2006); #7,741,104 (2010)