H. Ruley
Last active: 2/15/2016

Profile

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.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Cell-permeable parkin proteins suppress Parkinson disease-associated phenotypes in cultured cells and animals. Duong T, Kim J, Ruley HE, Jo D (2014) PLoS One 9(7): e102517
    › Primary publication · 25019626 (PubMed) · PMC4097392 (PubMed Central)
  2. The effect of intracellular protein delivery on the anti-tumor activity of recombinant human endostatin. Lim J, Duong T, Lee G, Seong BL, El-Rifai W, Ruley HE, Jo D (2013) Biomaterials 34(26): 6261-71
    › Primary publication · 23714245 (PubMed)
  3. Antitumor activity of cell-permeable RUNX3 protein in gastric cancer cells. Lim J, Duong T, Do N, Do P, Kim J, Kim H, El-Rifai W, Ruley HE, Jo D (2013) Clin Cancer Res 19(3): 680-90
    › Primary publication · 23230322 (PubMed) · PMC4039637 (PubMed Central)
  4. Antitumor activity of cell-permeable p18(INK4c) with enhanced membrane and tissue penetration. Lim J, Kim J, Duong T, Lee G, Kim J, Yoon J, Kim J, Kim H, Ruley HE, El-Rifai W, Jo D (2012) Mol Ther 20(8): 1540-9
    › Primary publication · 22617107 (PubMed) · PMC3412482 (PubMed Central)
  5. Cutting edge: the "death" adaptor CRADD/RAIDD targets BCL10 and suppresses agonist-induced cytokine expression in T lymphocytes. Lin Q, Liu Y, Moore DJ, Elizer SK, Veach RA, Hawiger J, Ruley HE (2012) J Immunol 188(6): 2493-7
    › Primary publication · 22323537 (PubMed) · PMC3294148 (PubMed Central)
  6. Cell-permeable NM23 blocks the maintenance and progression of established pulmonary metastasis. Lim J, Jang G, Kang S, Lee G, Nga do TT, Phuong do TL, Kim H, El-Rifai W, Ruley HE, Jo D (2011) Cancer Res 71(23): 7216-25
    › Primary publication · 21987726 (PubMed)
  7. Observational fear learning involves affective pain system and Cav1.2 Ca2+ channels in ACC. Jeon D, Kim S, Chetana M, Jo D, Ruley HE, Lin SY, Rabah D, Kinet JP, Shin HS (2010) Nat Neurosci 13(4): 482-8
    › Primary publication · 20190743 (PubMed) · PMC2958925 (PubMed Central)
  8. Dyggve-Melchior-Clausen syndrome: chondrodysplasia resulting from defects in intracellular vesicle traffic. Osipovich AB, Jennings JL, Lin Q, Link AJ, Ruley HE (2008) Proc Natl Acad Sci U S A 105(42): 16171-6
    › Primary publication · 18852472 (PubMed) · PMC2571016 (PubMed Central)
  9. Subunit 1 of the prefoldin chaperone complex is required for lymphocyte development and function. Cao S, Carlesso G, Osipovich AB, Llanes J, Lin Q, Hoek KL, Khan WN, Ruley HE (2008) J Immunol 181(1): 476-84
    › Primary publication · 18566413 (PubMed)
  10. Genome maintenance and mutagenesis in embryonic stem cells. Lin Q, Donahue SL, Ruley HE (2006) Cell Cycle 5(23): 2710-4
    › Primary publication · 17172854 (PubMed)
  11. Mutagenesis of diploid mammalian genes by gene entrapment. Lin Q, Donahue SL, Moore-Jarrett T, Cao S, Osipovich AB, Ruley HE (2006) Nucleic Acids Res 34(20): e139
    › Primary publication · 17062627 (PubMed) · PMC1635309 (PubMed Central)
  12. Carcinogens induce genome-wide loss of heterozygosity in normal stem cells without persistent chromosomal instability. Donahue SL, Lin Q, Cao S, Ruley HE (2006) Proc Natl Acad Sci U S A 103(31): 11642-6
    › Primary publication · 16868089 (PubMed) · PMC1544223 (PubMed Central)
  13. Post-entrapment genome engineering: first exon size does not affect the expression of fusion transcripts generated by gene entrapment. Osipovich AB, Singh A, Ruley HE (2005) Genome Res 15(3): 428-35
    › Primary publication · 15741512 (PubMed) · PMC551569 (PubMed Central)
  14. Discovery of mammalian genes that participate in virus infection. Organ EL, Sheng J, Ruley HE, Rubin DH (2004) BMC Cell Biol 5(1): 41
    › Primary publication · 15522117 (PubMed) · PMC534806 (PubMed Central)
  15. Enhanced cell-permeant Cre protein for site-specific recombination in cultured cells. Lin Q, Jo D, Gebre-Amlak KD, Ruley HE (2004) BMC Biotechnol : 25
    › Primary publication · 15500682 (PubMed) · PMC529453 (PubMed Central)
  16. Mutations in the IGF-II pathway that confer resistance to lytic reovirus infection. Sheng J, Organ EL, Hao C, Wells KS, Ruley HE, Rubin DH (2004) BMC Cell Biol : 32
    › Primary publication · 15333144 (PubMed) · PMC517494 (PubMed Central)
  17. Activation of cryptic 3' splice sites within introns of cellular genes following gene entrapment. Osipovich AB, White-Grindley EK, Hicks GG, Roshon MJ, Shaffer C, Moore JH, Ruley HE (2004) Nucleic Acids Res 32(9): 2912-24
    › Primary publication · 15155860 (PubMed) · PMC419606 (PubMed Central)
  18. The high-mobility-group box protein SSRP1/T160 is essential for cell viability in day 3.5 mouse embryos. Cao S, Bendall H, Hicks GG, Nashabi A, Sakano H, Shinkai Y, Gariglio M, Oltz EM, Ruley HE (2003) Mol Cell Biol 23(15): 5301-7
    › Primary publication · 12861016 (PubMed) · PMC165710 (PubMed Central)
  19. Cell cycle-dependent transduction of cell-permeant Cre recombinase proteins. Jo D, Lin Q, Nashabi A, Mays DJ, Unutmaz D, Pietenpol JA, Ruley HE (2003) J Cell Biochem 89(4): 674-87
    › Primary publication · 12858334 (PubMed)
  20. 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. Roshon M, DeGregori JV, Ruley HE (2003) BMC Genomics 4(1): 2
    › Primary publication · 12546712 (PubMed) · PMC149352 (PubMed Central)
  21. Protein arginine methyltransferase I: substrate specificity and role in hnRNP assembly. Pawlak MR, Banik-Maiti S, Pietenpol JA, Ruley HE (2002) J Cell Biochem 87(4): 394-407
    › Primary publication · 12397599 (PubMed)
  22. PUM2, a novel murine puf protein, and its consensus RNA-binding site. White EK, Moore-Jarrett T, Ruley HE (2001) RNA 7(12): 1855-66
    › Primary publication · 11780640 (PubMed) · PMC1370223 (PubMed Central)
  23. Epigenetic regulation of gene structure and function with a cell-permeable Cre recombinase. Jo D, Nashabi A, Doxsee C, Lin Q, Unutmaz D, Chen J, Ruley HE (2001) Nat Biotechnol 19(10): 929-33
    › Primary publication · 11581657 (PubMed)
  24. Functional genomics of the murine immune system. Ruley HE (2001) Immunol Res 23(2-3): 289-99
    › Primary publication · 11444394 (PubMed)
  25. Ly108: a new member of the mouse CD2 family of cell surface proteins. Peck SR, Ruley HE (2000) Immunogenetics 52(1-2): 63-72
    › Primary publication · 11132158 (PubMed)
  26. Arginine N-methyltransferase 1 is required for early postimplantation mouse development, but cells deficient in the enzyme are viable. Pawlak MR, Scherer CA, Chen J, Roshon MJ, Ruley HE (2000) Mol Cell Biol 20(13): 4859-69
    › Primary publication · 10848611 (PubMed) · PMC85937 (PubMed Central)
  27. hnRNP C is required for postimplantation mouse development but Is dispensable for cell viability. Williamson DJ, Banik-Maiti S, DeGregori J, Ruley HE (2000) Mol Cell Biol 20(11): 4094-105
    › Primary publication · 10805751 (PubMed) · PMC85779 (PubMed Central)
  28. Fus deficiency in mice results in defective B-lymphocyte development and activation, high levels of chromosomal instability and perinatal death. Hicks GG, Singh N, Nashabi A, Mai S, Bozek G, Klewes L, Arapovic D, White EK, Koury MJ, Oltz EM, Van Kaer L, Ruley HE (2000) Nat Genet 24(2): 175-9
    › Primary publication · 10655065 (PubMed)
  29. Endogenous p53 regulation and function in early stage Friend virus-induced tumor progression differs from that following DNA damage. Kelley LL, Hicks GG, Hsieh FF, Prasher JM, Green WF, Miller MD, Eide EJ, Ruley HE (1998) Oncogene 17(9): 1119-30
    › Primary publication · 9764822 (PubMed)
  30. An enhancer element in the EphA2 (Eck) gene sufficient for rhombomere-specific expression is activated by HOXA1 and HOXB1 homeobox proteins. Chen J, Ruley HE (1998) J Biol Chem 273(38): 24670-5
    › Primary publication · 9733765 (PubMed)
  31. Functional genomics in mice by tagged sequence mutagenesis. Hicks GG, Shi EG, Li XM, Li CH, Pawlak M, Ruley HE (1997) Nat Genet 16(4): 338-44
    › Primary publication · 9241269 (PubMed)
  32. Transcriptional specificity of the pluripotent embryonic stem cell. Scherer CA, Chen J, Nachabeh A, Hopkins N, Ruley HE (1996) Cell Growth Differ 7(10): 1393-401
    › Primary publication · 8891343 (PubMed)
  33. p53 and response to chemotherapy and radiotherapy. Ruley HE (1996) Important Adv Oncol : 37-56
    › Primary publication · 8791127 (PubMed)
  34. Germ-line inactivation of the murine Eck receptor tyrosine kinase by gene trap retroviral insertion. Chen J, Nachabah A, Scherer C, Ganju P, Reith A, Bronson R, Ruley HE (1996) Oncogene 12(5): 979-88
    › Primary publication · 8649815 (PubMed)
  35. H2-M mutant mice are defective in the peptide loading of class II molecules, antigen presentation, and T cell repertoire selection. Martin WD, Hicks GG, Mendiratta SK, Leva HI, Ruley HE, Van Kaer L (1996) Cell 84(4): 543-50
    › Primary publication · 8598041 (PubMed)
  36. Retrovirus gene traps. Hicks GG, Shi EG, Chen J, Roshon M, Williamson D, Scherer C, Ruley HE (1995) Methods Enzymol : 263-75
    › Primary publication · 8531691 (PubMed)
  37. Enrichment of insertional mutants following retrovirus gene trap selection. Chang W, Hubbard SC, Friedel C, Ruley HE (1993) Virology 193(2): 737-47
    › Primary publication · 8460482 (PubMed)
  38. p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Lowe SW, Ruley HE, Jacks T, Housman DE (1993) Cell 74(6): 957-67
    › Primary publication · 8402885 (PubMed)
  39. Stabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis. Lowe SW, Ruley HE (1993) Genes Dev 7(4): 535-45
    › Primary publication · 8384579 (PubMed)
  40. A murine homolog of the yeast RNA1 gene is required for postimplantation development. DeGregori J, Russ A, von Melchner H, Rayburn H, Priyaranjan P, Jenkins NA, Copeland NG, Ruley HE (1994) Genes Dev 8(3): 265-76
    › Primary publication · 8314081 (PubMed)
  41. 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. Kelley LL, Green WF, Hicks GG, Bondurant MC, Koury MJ, Ruley HE (1994) Mol Cell Biol 14(6): 4183-92
    › Primary publication · 8196656 (PubMed) · PMC358784 (PubMed Central)
  42. Abrogation of oncogene-associated apoptosis allows transformation of p53-deficient cells. Lowe SW, Jacks T, Housman DE, Ruley HE (1994) Proc Natl Acad Sci U S A 91(6): 2026-30
    › Primary publication · 8134344 (PubMed) · PMC43302 (PubMed Central)
  43. Generation of Chinese hamster ovary cell glycosylation mutants by retroviral insertional mutagenesis. Integration into a discrete locus generates mutants expressing high levels of N-glycolylneuraminic acid. Hubbard SC, Walls L, Ruley HE, Muchmore EA (1994) J Biol Chem 269(5): 3717-24
    › Primary publication · 8106417 (PubMed)
  44. p53 status and the efficacy of cancer therapy in vivo. Lowe SW, Bodis S, McClatchey A, Remington L, Ruley HE, Fisher DE, Housman DE, Jacks T (1994) Science 266(5186): 807-10
    › Primary publication · 7973635 (PubMed)
  45. Two serum response elements mediate transcriptional repression of human smooth muscle alpha-actin promoter in ras-transformed cells. Bushel P, Kim JH, Chang W, Catino JJ, Ruley HE, Kumar CC (1995) Oncogene 10(7): 1361-70
    › Primary publication · 7731687 (PubMed)
  46. Apoptosis and the prognostic significance of p53 mutation. Lowe SW, Bodis S, Bardeesy N, McClatchey A, Remington L, Ruley HE, Fisher DE, Jacks T, Pelletier J, Housman DE (1994) Cold Spring Harb Symp Quant Biol : 419-26
    › Primary publication · 7587096 (PubMed)
  47. Isolation of an autonomously replicating DNA fragment from the region of defective bacteriophage PBSX of Bacillus subtilis. Anderson LM, Ruley HE, Bott KF (1982) J Bacteriol 150(3): 1280-6
    › Primary publication · 6804442 (PubMed) · PMC216351 (PubMed Central)
  48. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Ruley HE (1983) Nature 304(5927): 602-6
    › Primary publication · 6308473 (PubMed)
  49. Clustered illegitimate recombination events in mammalian cells involving very short sequence homologies. Ruley HE, Fried M (1983) Nature 304(5922): 181-4
    › Primary publication · 6306477 (PubMed)
  50. Sequence repeats in a polyoma virus DNA region important for gene expression. Ruley HE, Fried M (1983) J Virol 47(1): 233-7
    › Primary publication · 6306275 (PubMed) · PMC255237 (PubMed Central)
  51. Structural and biological analysis of integrated polyoma virus DNA and its adjacent host sequences cloned from transformed rat cells. Hayday A, Ruley HE, Fried M (1982) J Virol 44(1): 67-77
    › Primary publication · 6292505 (PubMed) · PMC256241 (PubMed Central)
  52. Use of a cellular polyadenylation signal by viral transcripts in polyoma virus transformed cells. Ruley HE, Lania L, Chaudry F, Fried M (1982) Nucleic Acids Res 10(15): 4515-24
    › Primary publication · 6290990 (PubMed) · PMC321108 (PubMed Central)
  53. In vitro establishment is not a sufficient prerequisite for transformation by activated ras oncogenes. Franza BR, Maruyama K, Garrels JI, Ruley HE (1986) Cell 44(3): 409-18
    › Primary publication · 3510745 (PubMed)
  54. Adenovirus E1A coding sequences that enable ras and pmt oncogenes to transform cultured primary cells. Zerler B, Moran B, Maruyama K, Moomaw J, Grodzicker T, Ruley HE (1986) Mol Cell Biol 6(3): 887-99
    › Primary publication · 3022137 (PubMed) · PMC367589 (PubMed Central)
  55. Two regions of the adenovirus early region 1A proteins are required for transformation. Whyte P, Ruley HE, Harlow E (1988) J Virol 62(1): 257-65
    › Primary publication · 2960834 (PubMed) · PMC250526 (PubMed Central)
  56. Expression of the adenovirus E1A oncogene during cell transformation is sufficient to induce susceptibility to lysis by host inflammatory cells. Cook JL, Walker TA, Lewis AM, Ruley HE, Graham FL, Pilder SH (1986) Proc Natl Acad Sci U S A 83(18): 6965-9
    › Primary publication · 2944117 (PubMed) · PMC386632 (PubMed Central)
  57. myc and E1A oncogenes alter the responses of PC12 cells to nerve growth factor and block differentiation. Maruyama K, Schiavi SC, Huse W, Johnson GL, Ruley HE (1987) Oncogene 1(4): 361-7
    › Primary publication · 2838784 (PubMed)
  58. Rescue of cells from ras oncogene-induced growth arrest by a second, complementing, oncogene. Hirakawa T, Ruley HE (1988) Proc Natl Acad Sci U S A 85(5): 1519-23
    › Primary publication · 2830621 (PubMed) · PMC279804 (PubMed Central)
  59. Role of c-myc in the transformation of REF52 cells by viral and cellular oncogenes. Kohl NE, Ruley HE (1987) Oncogene 2(1): 41-8
    › Primary publication · 2830582 (PubMed)
  60. The structure and function of the integrated polyoma virus DNA in 82-rat and 53-rat transformed cells. Ruley HE, Chaudry F, Read M, Lania L, Fried M (1988) J Gen Virol : 197-207
    › Primary publication · 2826666 (PubMed)
  61. Transcription from the stromelysin promoter is induced by interleukin-1 and repressed by dexamethasone. Frisch SM, Ruley HE (1987) J Biol Chem 262(34): 16300-4
    › Primary publication · 2824488 (PubMed)
  62. Identification of cellular promoters by using a retrovirus promoter trap. von Melchner H, Ruley HE (1989) J Virol 63(8): 3227-33
    › Primary publication · 2545900 (PubMed) · PMC250892 (PubMed Central)
  63. Isolation of cellular promoters by using a retrovirus promoter trap. von Melchner H, Reddy S, Ruley HE (1990) Proc Natl Acad Sci U S A 87(10): 3733-7
    › Primary publication · 2339116 (PubMed) · PMC53977 (PubMed Central)
  64. Structure of the human smooth muscle alpha-actin gene. Analysis of a cDNA and 5' upstream region. Reddy S, Ozgur K, Lu M, Chang W, Mohan SR, Kumar CC, Ruley HE (1990) J Biol Chem 265(3): 1683-7
    › Primary publication · 2295650 (PubMed)
  65. Retroviruses as genetic tools to isolate transcriptionally active chromosomal regions. von Melchner H, Ruley HE (1990) Environ Health Perspect : 141-8
    › Primary publication · 2272309 (PubMed) · PMC1568027 (PubMed Central)
  66. Transforming collaborations between ras and nuclear oncogenes. Ruley HE (1990) Cancer Cells 2(8-9): 258-68
    › Primary publication · 2223387 (PubMed)
  67. Massive accumulation of neutral lipids in cells conditionally transformed by an activated H-ras oncogene. Hirakawa T, Maruyama K, Kohl NE, Kodama T, Ruley HE (1991) Oncogene 6(2): 289-95
    › Primary publication · 2000221 (PubMed)
  68. Selective targeting of gene products with the megakaryocyte platelet factor 4 promoter. Ravid K, Beeler DL, Rabin MS, Ruley HE, Rosenberg RD (1991) Proc Natl Acad Sci U S A 88(4): 1521-5
    › Primary publication · 1899930 (PubMed) · PMC51051 (PubMed Central)
  69. Mechanisms of oncogene cooperation: activation and inactivation of a growth antagonist. Ragozzino MM, Kuo A, DeGregori J, Kohl N, Ruley HE (1991) Environ Health Perspect : 97-103
    › Primary publication · 1837777 (PubMed) · PMC1568054 (PubMed Central)
  70. Retrovirus promoter-trap vector to induce lacZ gene fusions in mammalian cells. Reddy S, DeGregori JV, von Melchner H, Ruley HE (1991) J Virol 65(3): 1507-15
    › Primary publication · 1704929 (PubMed) · PMC239931 (PubMed Central)
  71. Fluorescence-activated sorting of totipotent embryonic stem cells expressing developmentally regulated lacZ fusion genes. Reddy S, Rayburn H, von Melchner H, Ruley HE (1992) Proc Natl Acad Sci U S A 89(15): 6721-5
    › Primary publication · 1495960 (PubMed) · PMC49575 (PubMed Central)
  72. Selective disruption of genes expressed in totipotent embryonal stem cells. von Melchner H, DeGregori JV, Rayburn H, Reddy S, Friedel C, Ruley HE (1992) Genes Dev 6(6): 919-27
    › Primary publication · 1317320 (PubMed)