Biomedical Research Education & Training
Faculty Member

Ruley, H. Earl, Ph.D.
Professor of Pathology, Microbiology and Immunology

Lab Url: N/A

Phone Number: 615-343-1379

Email Address: earl.ruley@Vanderbilt.Edu

Ruley, H.'s picture
Academic history
B.A., Stanford University, Stanford, CA
Ph.D., University of North Carolina, Chapel Hill, NC
Postdoc, Imperial Cancer Research Fund, London
Postdoc, Cold Spring Harbor Laboratory, CSH, NY

Office Address   Mailing Address

AA-4210B Medical Center North

A-4210A MCN 2363

Research Keywords
functional genomics, RNA, oncogene, tumor suppressor, Biochemistry, Cancer, Developmental biology, DNA repair, Enzyme action, Gene regulation, Genetics, Genomics, Immortalization, Knockout, Mass spectroscopy, Microbiology, Mouse, Proteomics, Stem cells, Transformation, Virus

Research Specialty
Genetic analysis of growth control and development

Research Description
My laboratory uses genetic and biochemical approaches to study mechanisms important in growth control and cancer. We have developed gene trapping strategies for genome-wide, biallelic mutagenesis of mammalian cells. Mutations in embryonic stem cells that affect specific genes of interest may be introduced into the germline; alternatively biallelic mutagens may be used in phenotype driven screens to identify genes responsible for recessive phenotypes in mammalian cells. We have used the to first approach to generate mice and cells defective in genes that are potentially involved in post-transcriptional gene regulation, [Ran GTPase activating protein, hnRNP A2/B1, hnRNP C, hnRNP U, TLS/Fus (hnRNP P2) and arginine methytransferase 1 (Prmt1)]. The genetic analysis of TLS/Fus, a gene translocated in human cancer, led to the unexpected discovery implicating this RNA binding protein in the maintenance of genome stability. The second approach has been used to identify candidate genes involved in Reovirus infection.
Studies to develop gene trap vectors provided basic information about transcript quality control, notably exon definition and nonsense-mediated decay, that govern the expression of gene segments inserted at ectopic sites in the genome. In addition, the collection of mutant stem cells has been used in genome-wide studies of spontaneous and carcinogen-induced LOH (loss of heterozygosity). The extent of LOH was remarkably high approaching 1% of the genome after brief exposure to nontoxic levels of carcinogens. These results highlight the importance of LOH as a somatic mutation and suggest that much of the LOH in cancer cells may result from prior exposure to genotoxic agents rather than from a state of chromosome instability during carcinogenesis. In addition this work underscores the importance of genome maintenance in stem cells that serve as the normal cellular precursors to cancer. Current work in the lab is investigating the mechanisms of carcinogen-induced LOH.

Donahue, SL, Lin, Q, Cao, S, Ruley, HE. Carcinogens induce genome-wide loss of heterozygosity in normal stem cells without persistent chromosomal instability. Proc Natl Acad Sci U S A, 103(31), 11642-6, 2006 PMCID:1544223

Lin, Q, Donahue, SL, Moore-Jarrett, T, Cao, S, Osipovich, AB, Ruley, HE. Mutagenesis of diploid mammalian genes by gene entrapment. Nucleic Acids Res, 34(20), e139, 2006 PMCID:1635309

Lin, Q, Donahue, SL, Ruley, HE. Genome maintenance and mutagenesis in embryonic stem cells. Cell Cycle, 5(23), 2710-4, 2006

Osipovich, AB, Singh, A, Ruley, HE. Post-entrapment genome engineering: first exon size does not affect the expression of fusion transcripts generated by gene entrapment. Genome Res, 15(3), 428-35, 2005 PMCID:551569

Roshon, MJ, Ruley, HE. Hypomorphic mutation in hnRNP U results in post-implantation lethality. Transgenic Res, 14(2), 179-92, 2005

Lin, Q, Jo, D, Gebre-Amlak, KD, Ruley, HE. Enhanced cell-permeant Cre protein for site-specific recombination in cultured cells. BMC Biotechnol, 4, 25, 2004 PMCID:529453

Organ, EL, Sheng, J, Ruley, HE, Rubin, DH. Discovery of mammalian genes that participate in virus infection. BMC Cell Biol, 5(1), 41, 2004 PMCID:534806

Osipovich, AB, White-Grindley, EK, Hicks, GG, Roshon, MJ, Shaffer, C, Moore, JH, Ruley, HE. Activation of cryptic 3'' splice sites within introns of cellular genes following gene entrapment. Nucleic Acids Res, 32(9), 2912-24, 2004 PMCID:419606

Sheng, J, Organ, EL, Hao, C, Wells, KS, Ruley, HE, Rubin, DH. Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection. BMC Cell Biol, 5, 32, 2004 PMCID:517494

Cao, Shang, Bendall, Heather, Hicks, Geoffrey G, Nashabi, Abudi, Sakano, Hitoshi, Shinkai, Yoichi, Gariglio, Marisa, Oltz, Eugene M, Ruley, H Earl. The high-mobility-group box protein SSRP1/T160 is essential for cell viability in day 3.5 mouse embryos. Mol Cell Biol, 23(15), 5301-7, 2003 PMCID:165710

Jo, Daewoong, Lin, Qing, Nashabi, Abudi, Mays, Deborah J, Unutmaz, Derya, Pietenpol, Jennifer A, Ruley, H Earl. Cell cycle-dependent transduction of cell-permeant Cre recombinase proteins. J Cell Biochem, 89(4), 674-87, 2003

Roshon, Michael, DeGregori, James V, Ruley, H Earl. Gene trap mutagenesis of hnRNP A2/B1: a cryptic 3' splice site in the neomycin resistance gene allows continued expression of the disrupted cellular gene. BMC Genomics, 4(1), 2, 2003 PMCID:149352

Pawlak, Maciej R, Banik-Maiti, Sarbani, Pietenpol, Jennifer A, Ruley, H Earl. Protein arginine methyltransferase I: substrate specificity and role in hnRNP assembly. J Cell Biochem, 87(4), 394-407, 2002

Jo, D, Nashabi, A, Doxsee, C, Lin, Q, Unutmaz, D, Chen, J, Ruley, H E. Epigenetic regulation of gene structure and function with a cell-permeable Cre recombinase. Nat Biotechnol, 19(10), 929-33, 2001

Ruley, H E. Functional genomics of the murine immune system. Immunol Res, 23(2-3), 289-99, 2001

White, E K, Moore-Jarrett, T, Ruley, H E. PUM2, a novel murine puf protein, and its consensus RNA-binding site. RNA, 7(12), 1855-66, 2001 PMCID:1370223

Williamson, D.J., Banik-Maiti, S., DeGregori, J., and Ruley, H.E. (2000) hnRNP C is required for post-implantation mouse development but is dispensable for cell viability. Mol. Cell. Biol. 20:4094-4105.

Hicks, G.G., Singh, N, Nashabi, A., Mai, S., Gracjan Bozek, Klewes, L., Arapovic, D., White, E.K., Koury, M.J., Oltz, E.M., Van Kaer, L.V., and Ruley, H.E. Fus deficiency in mice results in defective B lymphocyte development and activation, high levels of chromosomal instability and perinatal death. Nature Genetics , 24, 176-179 , 2000

Pawlak, M.R., Scherer, C.A., Chen, J., Roshon, M.J., Ruley, H.E. Arginine methyltransferase 1 is required for early post- implantation mouse development, but cells deficient in the enzyme are viable. Mol. Cell. Biol, 20, 4859-4869, 2000

Peck, S R, Ruley, H E. Ly108: a new member of the mouse CD2 family of cell surface proteins. Immunogenetics, 52(1-2), 63-72, 2000

Williamson, D J, Banik-Maiti, S, DeGregori, J, Ruley, H E. hnRNP C is required for postimplantation mouse development but Is dispensable for cell viability. Mol Cell Biol, 20(11), 4094-105, 2000 PMCID:85779

Chen, J, Ruley, H E. An enhancer element in the EphA2 (Eck) gene sufficient for rhombomere-specific expression is activated by HOXA1 and HOXB1 homeobox proteins. J Biol Chem, 273(38), 24670-5, 1998

Chen, J. and Ruley, H.E. An enhancer element in the EphA2 (Eck) gene is sufficient for rhombomere-specific gene expression and is activated by HOXA1 and HOXB1 homeobox proteins. J. Biol. Chem., 273, 64670-64675, 1998

Kelly, L.L., Hicks, G.G., Hsieh, F.F., Green, W.F., Miller, M.D., Eide, E.J. and Ruley, H.E. Wild-type p53 regulation and function in early stage tumor progression differs from that following DNA damage. Oncogene, 17, 1119-1130, 1998

Hicks, G.G., Chen, J., and H.E. Ruley (1997) Production and use of Retroviruses. Culture of Specialized Cells Series, Volume 4: DNA Transfer to Cultured Cells. John Wiley and Sons, Inc. Katya Revid and R. Ian Freshney, eds.

Ruley, H.E. (1997) p53 and response to chemotherapy and radiotherapy. In: Cancer, Principles and Practice of Oncology, Updates DeVita, V.T., Hellman, S. and Rosenberg, S.A. eds. Lippincott-Raven Co., Philadelphia.

Hicks, G G, Shi, E G, Li, X M, Li, C H, Pawlak, M, Ruley, H E. Functional genomics in mice by tagged sequence mutagenesis. Nat Genet, 16(4), 338-44, 1997

Hicks, G.G., Shi, E., Li, X., Li, C., Pawlak, M. and Ruley, H.E. Functional Genomics in Mice by Tagged Sequence Mutagenesis. Nature Genetics , 16, 338-344, 1997

Chen, J, Nachabah, A, Scherer, C, Ganju, P, Reith, A, Bronson, R, Ruley, H E. Germ-line inactivation of the murine Eck receptor tyrosine kinase by gene trap retroviral insertion. Oncogene, 12(5), 979-88, 1996

Chen, J., Nachebeh, A., Scherer, C., Ganju, P., Reith, A., Bronson, R., Ruley, H.E. Germ-line inactivation of the murine Eck receptor tyrosine kinase gene by retroviral insertion. Oncogene , 12, 979-988, 1996

Martin, W D, Hicks, G G, Mendiratta, S K, Leva, H I, Ruley, H E, Van Kaer, L. H2-M mutant mice are defective in the peptide loading of class II molecules, antigen presentation, and T cell repertoire selection. Cell, 84(4), 543-50, 1996

Martin, W. D., Hicks, G.G., Mediratta, S.K., Leva, H.I., Ruley, H.E., and Van Kaer, L. H-2M mutant mice are defective in the peptide loading of class II molecules, antigen presentation, and T cell repertoire selection. Cell, 84, 543-550, 1996

Ruley, H E. p53 and response to chemotherapy and radiotherapy. Important Adv Oncol, 37-56, 1996

Ruley, H.E. p53 and response to chemotherapy and radiotherapy. Important Advances in Oncology 1996. DeVita, V.T., Hellman, S. and Rosenberg, S.A. eds. J.B. Lippincott Co., Philadelphia, 37-56, 1996

Scherer, C.A., Chen, J., Nachabeh, A., Hopkins, N., and Ruley, H.E. Transcriptional specificity of the pluripotent embryonic stem cell. Cell Growth Diff., 7, 1393-1401, 1996

Bushel, P., Kim, J.H., Chang, W., Catino, J.J., Ruley, H.E. and Kumar, C.C.(1995) Two serum response elements in the human smooth muscle

Lowe, S.W. and Ruley. H.E.(1995) p53 dependent apoptosis in tumor progression and cancer therapy. in: Modern Cell Biology, John Wiley and Sons, Inc. New York. (in press).

Lowe, S.W. and Ruley. H.E.(1995) p53 dependent apoptosis in tumor progression and cancer therapy. in: Modern Cell Biology, John Wiley and Sons, Inc. New York. (in press).

Hicks, G G, Shi, E G, Chen, J, Roshon, M, Williamson, D, Scherer, C, Ruley, H E. Retrovirus gene traps. Methods Enzymol, 254, 263-75, 1995

Ruley, H.E. (1994) Oncogenes and Nervous System Tumors. In: Neurosurgery. R. H Wilkins and S.S. Rengachary, eds. McGraw Hill Publishing Co., New York (in press).

Chen, J., Degregori, J., Hicks, G., Roshon, M., Shi, E-G, Scherer, S. and Ruley H.E. Gene Trap Retroviruses. Meth. Mol. Genet., 4, 123-140, 1994

DeGregori, J, Russ, A, von Melchner, H, Rayburn, H, Priyaranjan, P, Jenkins, N A, Copeland, N G, Ruley, H E. A murine homolog of the yeast RNA1 gene is required for postimplantation development. Genes Dev, 8(3), 265-76, 1994

DeGregori, J.V., Russ, A., von Melchner, H., Rayburn, H., Priyaranjan, P., Jenkins, N., Copeland, N.and Ruley, H.E. A murine homolog of the yeast RNA1 gene is required for postimplantation development. Genes and Dev, 8, 265-276, 1994

Hubbard, S.C., Walls, L., Ruley, H.E., and Muchmore, E.A. Generation of Chineses hamster ovary cell glycosylation mutants by retroviral insertional mutagenesis: integration into a discrete locus generates mutants expressing high levels of N-glycolyneuraminic acid. J. Biol. Chem., 269, 3713-3724, 1994

Kelley, L L, Green, W F, Hicks, G G, Bondurant, M C, Koury, M J, Ruley, H E. Apoptosis in erythroid progenitors deprived of erythropoietin occurs during the G1 and S phases of the cell cycle without growth arrest or stabilization of wild-type p53. Mol Cell Biol, 14(6), 4183-92, 1994 PMCID:358784

Kelly, L.L., Green, W.F., Hicks, G.G., Bondurant, M.C., Koury, M.J. and Ruley, H.E. Apoptosis in erythroid progenitors deprived of erythropoietin occurs during G1 and S phases of the cell cycle without growth arrest or stabilization of wild-type p53. Mol. Cell. Biol., 14, 4183-4192, 1994

Lowe, S.W., Bodis, S., McClatchey, A., Remington, L., Ruley, H.E., Fisher, D., Housman, D., and Jacks, T. p53 status and the efficacy of cancer therapy in vivo. Science, 266, 807-810, 1994

Lowe, S.W., Jacks, T., and Housman and Ruley, H.E. Abrogation of oncogene associated apoptosis allows transformation of p53 deficient cells. Proc. Natl. Acad. Sci. (USA), 91, 2026-2030, 1994

Chang, W., Fridel, C. and Ruley, H.E. Enrichment of insertional mutants following retrovirus gene trap selection. Virology, 193, 737-747, 1993

Lowe, S.W. and Ruley, H.E. Stabilization of the p53 tumor suppressor is induced by adenovirus-5 E1A and accompanies apoptosis. Genes Dev., 7, 535-545, 1993

Lowe, S.W., Ruley, H.E., Jacks, T., and Housman, D.E. p53-dependent apoptosis modulates the cytoxicity of anticancer agents. Cell, 74, 957-967, 1993

Reddy, S., Rayburn, H., von Melchner, H., and Ruley, H.E. Fluorescence activated sorting of totipotent embryonic stem cells expressing developmentally regulated lacZ fusion genes. Proc. Natl. Acad. Sci. U.S.A, 89, 6721-6725, 1992

von Melchner, H., DeGregori, J.V., Raybrun, H., Reddy, S. ,Fridel, C., and Ruley, H.E. Selective disruption of genes expressed in totipotent embryonal stem cells. Genes Dev., 6, 919-926, 1992

Ravid, K., Beeler, D.L. Rabin, M.S., Ruley, H.E. and Rosenberg, R.D. Selective targeting of gene products with megakarocyte PF4 promoter. Proc. Natl Acad. Sci. U.S.A., 88, 1521-1525, 1991

Reddy, S., DeGregori, J.V., von Melchner, H. and Ruley, H.E. Retrovirus promoter trap vector to induce lacZ gene fusions in mammalian cells. J. Virol, 65, 1507-1515, 1991

Hirakawa, T., Maruyama, K., Kohl, N.E., Kodama, T. and Ruley, H.E. Massive accumulation of neutral lipids in cells conditionally transformed by an activated H-ras oncogene. Oncogene , 6, 289-295, 1990

Hirakawa, T. and H.E. Ruley. Rescue of cells from ras-oncogene induced growth arrest by a second, complementing oncogene. Proc. Natl. Acad. Sci. (USA), 85, 1519-1523, 1988

Whyte, P., Ruley, H.E. and Harlow, E. Two regions of the adenovirus early region proteins required for transformation. J. Virol., 62, 257-265, 1988

Franza, B.R. Jr.,K. Maruyama, J.I.Garrels, and H.E. Ruley. In vitro establishment is not a sufficient prerequisite for transformation by activated ras oncogenes. Cell, 44, 409-418, 1986

Zerler, B., B.Moran, K.Maruyama, J.Moomaw, T.Grodzicker, and H.E.Ruley. Adenovirus E1A coding sequences that enable ras and pmt oncogenes to transform cultured primary cells. Mol. Cell Biol., 6, 887-899, 1986

Ruley, H.E. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature, 304, 602-606, 1983

Ruley, H.E. and Fried, M. Sequence repeats in a polyoma virus DNA region important for gene expression. J. Virol. , 47, 233-237, 1983

Ruley, H.E. and Fried, M. Clustered illegitimate recombination events in mammalian cells involving very short sequence homologies. Nature, 304, 181-184, 1983

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