Joe W. Gray, Ph.D.

Joe Gray, PhD

He is Principal Investigator of a NationalCancer Institute Center for Cancer Systems Biology 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 and devise robust control strategies; PI of a National Institutes of Health Library ofIntegrated 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 observable phenotypes; and Co-PI of a Serial Measurement of Molecular and Architectural Responses to Therapy (SMMART) Treatments program that focuses on identification of mechanisms by which advanced individual cancers of the breast, prostate, pancreas and AML become resistant to treatment to better treat the individual cancers. 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 and he is an elected member of the National Academy of Medicine. He serves as a United States Councilor to the Radiation Effects Research Foundation (RERF), Hiroshima, Japan.

Major awards include the Radiation Research Society Research Award (1985), the E.O. Lawrence Award, United States Department of Energy (1986); Curt Stern Award, American Society for Human Genetics (2001); Honorary Doctorate, University of Tampere, Finland (2005); Brinker Award for Scientific Distinction, Susan G. Komen® Foundation (2007); Team Science Award, American Association for Cancer Research (2008); the Fulwyler Award, International Society for the Advancement of Cytometry (2010); the William L. McGuire Memorial Lecture Award, AACR San Antonio Breast Cancer Conference (2011) ; Lawrence Livermore National Laboratory Entrepreneur's Hall of Fame Honoree (2012); Simon M. Shubitz Award from the University of Chicago (2012); an Honorary Doctorate of Engineering, Colorado School of Mines (2012); the 18th Annual Alfred G. Knudson Award Lecture in Cancer Genetics (2014) and Fellow, American Association of Cancer Research Academy Class of 2016.

Contribution to Science
Dr. Gray's first major scientific contributions involved development of flow cytometric techniques for cell and genome analysis. These included techniques for high-speed chromosome sorting1-3, and BrdUrd/DNA analysis of cell proliferation4. Sorter-purified chromosomes were cloned to produce chromosome-specific DNA libraries that were distributed world-wide and were used to assemble early chromosome maps in the human genome project. Aspects of high speed sorting that they developed are now incorporated in all modern sorters.  BrdUrd/DNA analysis has become a standard technique for assessment of cell proliferation.

1.           Gray, J.W., Carrano, A.V., Steinmetz, L.L., Van Dilla, M.A., Moore, D.H. II, Mayall, B.H. and Mendelsohn, M.L. (1975) Chromosome measurement and sorting by flow systems. Proc. Natl. Acad. Sci. USA, 72:231-1234.

2.           Gray, J.W., Langlois, R.G., Carrano, A.V. and Van Dilla, M.A. (1979) High resolution chromosome analysis: One and two parameter flow cytometry. Chromosoma,73:9-27.

3.           Gray, J.W., Dean, P.N., Fuscoe, J.C., Peters, D.C., Trask, B., van den Engh, G., and Van Dilla, M.A. (1987) High speed chromosome sorting. Science, 238:323-9.

4.           Dolbeare, F., Gratzner, H., Pallavicini, M.G., Gray, J.W. (1983) Flow cytometric measurement of total DNA content and incorporated bromodeoxyuridine. Proc.Natl. Acad. Sci. USA, 80:5573-7. US Patent #4,780,406

The availability of chromosome specific libraries inspired the Gray and Pinkel Laboratories to develop fluorescence in situ hybridization (FISH) to stain specific chromosome regions5. FISH dramatically simplified metaphase chromosome classification and enabled detection of numerical and structural aberrations in interphase cells. Their papers describe the first uses of FISH for gene amplification (specifically ERBB26), gene deletion (specifically RB18) and translocation(specifically BCR-ABL7) in clinical samples. FISH has been licensed to Abbott Diagnostics and is now used world-wide for disease diagnosis, molecular assessment of chromosome abnormalities and analysis of the organization of interphase nuclei.

5.           Pinkel, D., Landegent, J., Collins, C., Fuscoe, J., Seagraves, R., Lucas, J., and Gray, J.W. (1988) Fluorescence in situ hybridization with human chromosome specificlibraries: Detection of trisomy 21 and translocations of chromosome 4. Proc.Natl. Acad. Sci. USA, 85:9138-42. US patent # 5,447,841, #6,500,612

6.           Kallioniemi,O.-P., Kallioniemi, A., Kurisu, W., Thor, A., Chen, L.-C., Smith, H. S., Waldman,F., Pinkel, D., Gray, J.W. (1992). ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridization. Proc. Natl. Acad. Sci. USA, 89:5321-25. US Patent #5,856,097

7.           Tkachuk, D.C., Westbrook, C.A., Andreeff, M., Donlon, T.A., Cleary, M.L., Suryanarayan, K., Homge, M., Redner, A., Gray, J.W., Pinkel, D. (1990) Detection of bcr-ablfusion in chronic myleogeneous leukemia by in situ hybridization. Science, 250:559-62.US Patent #6,280,929

8.           Kallioniemi, A., Kallioniemi, O.-P., Waldman, F.M., Chen, L.-C., Yu, L.-C., Fung, Y.K., Smith, H.S., Pinkel, D., Gray, J.W. (1992) Detection of retinoblastoma genecopy number in metaphase chromosomes and interphase nuclei by fluorescence insitu hybridization. Cytogenet. Cell Genet., 60:190-3.

Experience with FISH led the Gray, Pinkel and collaborating laboratories to the invention of comparative genomic hybridization (CGH) for genome-wide assessment of copy number abnormalities9-11. CGH enabled interpretation of previously intractable complex cancer genomes by mapping the aberrations on to representations of normal genomes. These studies inspired the Gray and Collins Laboratories to develop a genome sequencing based approach to assessment of copy number and genome structure abnormalities called End Sequence Profiling (ESP). ESP was based on mapping sequences from the ends of clones from tumor libraries onto a normal representation of the normal genome12. This approach is now the basis for paired end sequencing applications implemented using massively parallel sequencing.

9.           Kallioniemi, A., Kallioniemi, O.-P., Sudar, D., Rutovitz, D., Gray, J.W., Waldman, F., Pinkel, D. (1992) Comparative genomic hybridization for molecular cytogenetic analysis of solid tumors. Science, 258:818-21. US Patent #5,665,549

10.         Pinkel,D., Segraves, R., Sudar, D., Clark, S., Poole, I., Kowbel, D., Collins, C., Kuo, W.-L., Chen, C., Zhai, Y., Dairkee, S., Lejung, B., Gray, J., and Albertson, D. (1998) High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat. Genet., 20:207-11. US Patent #6,210,878

11.         Hodgson,G., Hager, J.H., Volik, S., Hariono, S., Wernick, M., Moore, D., Nowak, N., Albertson, D.G., Pinkel, D., Collins, C., Hanahan, D., Gray, J.W. (2001) Genome scanning with array CGH delineates regional alterations in murine islet carcinomas. Nat. Genet., 29(4):459-64.

12.         Volik, S., Zhao, S., Chin, K., Brebner, J.H., Herndon, D.R., Tao, Q., Kowbel, D., Huang, G., Lapuk, A., Kuo, W.-L., Magrane, G., de Jong, P., Gray, J.W. and Collins. C. (2003) End-sequence profiling: sequence-based analysis of aberrant genomes. Proc. Natl. Acad. Sci. USA, 100:7696-701. US Patent #6,785,614

Their applications of these approaches to human and model cancers revealed the remarkable genomic complexity that characterizes most solid tumors and demonstrated the presence of recurrent genome aberrations in a broad range of human cancers. In particular, they showed that human breast cancers pass through telomere crisis and become immortal during progression from usual ductal hyperplasia to carcinoma in situ13. This is important since it suggests strategies to prevent this critical transition. They also integrated diverse data types to identify breast and pancreatic cancer subtypes associated with disease progression and response to treatment14-16.

13.         Chin, K., de Solorzano, C.O., Knowles, D., Jones, A., Chou, W., Rodriguez, E.G., Kuo, W.-L., Ljung, B.M., Chew, K., Myambo, K., Miranda, M., Krig, S., Garbe, J., Stampfer, M., Yaswen, P., Gray, J.W., Lockett, S.J. (2004) In situ analyses of genome instability in breast cancer. Nat. Genet., 36:984-8.

14.         Collisson, E.A., Sadanandam, A., Olson, P., Gibb, W.J., Truitt, M., Gu, S., Cooc, J., Weinkle, J., Kim, G.E., Jakkula, L., Feiler, H.S., Ko, A.H., Olshen, A.B., Danenberg, K.L., Tempero, M.A., Spellman, P.T., Hanahan, D., Gray, J.W. (2011) Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy. Nature Med.,17:500-503. PMC3755490

15.         Chin, K., DeVries, S., Fridlyand, J., Spellman, P.T., Roydasgupta, R., Kuo, W.-L., Lapuk, A., Neve, R.M., Qian, Z., Ryder, T., Chen, F., Feiler, H., Tokuyasu, T.,Kingsley, C., Dairkee, S., Meng, Z., Chew, K., Pinkel, D., Jain, A., Ljung, B.M., Esserman, L., Albertson, D.G., Waldman, F.M., Gray, J.W. (2006) Genomic and transcriptional aberrations linked to breast cancer pathophysiologies. Cancer Cell, 10:529-41.

16.         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. (2013) Modeling precision treatment of breast cancer. Genome Biol., 14:R110. PMC3937590

Most recently, we have elucidated mechanisms of cancer progression and developed systems biology approaches for identification of molecular markers that predict and determine response to therapeutic treatment17,19. We are also developing aspects of the OHSU Center for Spatial Systems Biology to elucidate how genomic and epigenomic events influence the few Ǻngström to millimeter scale structures that enable function in cells and tissues18,20. These studies integrate results from measurements of the genome, proteome, and multiscale cellular and molecular structure and are directly relevant to the work.

17.         Heiser, L.M., Sadanandam, A., Kuo, W.-L., Benz, S.C., Goldstein, T.C., Ng, S., Gibb,W.J., Wang, N.J., Ziyad, S., Tong, F., Bayani, N., Hu, Z., Billig, J.I., Dueregger, A., Lewis, S., Jakkula, L., Korkola, J.E., Durinck, S., Pepin, F.,Guan, Y., Purdom, E., Neuvial, P., Bengtsson, H., Wood, K.W., Smith, P.G.,Vassilev, L.T., Hennessy, B.T., Greshock, J., Bachman, K.E., Hardwicke, M.A., Park, J.W., Marton, L.J., Wolf, D.M., Collisson, E.A., Neve, R.M., Mills, G.B.,Speed, T.P., Feiler, H.S., Wooster, R.F., Haussler, D., Stuart, J.M., Gray, J.W., Spellman, P.T. (2012) Subtype and pathway specific responses to anticancer compounds in breast cancer. Proc. Natl. Acad. Sci. USA, 109:2724-9. PMC3286973

18.         Nan X., Collisson, E.A., Lewis, S., Huang, J., Tamgüney, T.M., Liphardt, J.T., McCormick, F., Gray, J.W., Chu S. (2013) Single-molecule super resolution imaging allows quantitative analysis of RAF multimer formation and signaling. Proc. Natl. Acad. Sci. USA, 110:18519-24. PMC3831949

19.         Chang,Y.H., Korkola J., Amin D.N., Moasser M.M., Carmena J.M., Gray J.W., Tomlin C.J. (2015) Disentangling multidimensional spatio-temporal data into their common and aberrant responses. PLoS One,10: e0121607. PMC4406848

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

The following link is to publications by Joe Gray or publications linked to grants on which he was PI:

The Scopus h-index for Joe Gray is 101.