Joseph Landolph, PhD

Associate Professor of Molecular Microbiology & Immunology

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Overview

Joseph R. Landolph, Jr., Ph. D.,was born and raised in Clifton Heights, Pennsylvania, a suburb of Philadelphia, Pennsylvania. He graduated from Clifton Heights High School in Clifton Heights, Pennsylvania, in June, l966, as Valedictorian of his class. Dr. Landolph received a B. S.Degree in Chemistry from Drexel University in Phila., Pa. in l971, graduating second in his class of Chemistry Majors. He then received a Ph. D. in Chemistry, majoring in Biophysical and Physical Chemistry, from the Univ. of California at Berkeley in l976, studying under the late Professor Melvin Calvin (Member of the U. S. National Academy of Sciences and a Nobel Laureate). For his Ph. D. thesis, Dr. Landolph studied BaP metabolism and BaP-induced cytotoxicity/morphological transformation in mouse liver epithelial/fibroblastic cells. He performed postdoctoral study in chemical mutagenesis and chemically induced morphological and neoplastic transformation and chemical carcinogenesis from l977-1980 at the University of Southern California (USC) under the late Professor Charles Heidelberger, who was a Member of the U. S. National Academy of Sciences. Dr. Landolph was appointed Assistant Professsor of Microbiology and Pathology in l982, and promoted to Associate Professor in l9787. He is currently Associate Professor of Molecular Microbiology and Immunology and Pathology, and a Member of the USC/Norris Comprehensive Cancer Center at the Keck School of Medicine, Associate Professor of Molecular Pharmacology and Pharmaceutical Sciences of the School of Pharmacy, and a Member of the Free Radical Institute, at USC in Los Angeles, California. His research interests include the molecular mechanisms of the carcinogenicity of insoluble, carcinogenic nickel compounds and of soluble and insoluble, carcinogenic Cr(VI) compounds, and activation of oncogenes/inactivation of tumor suppressor genes and de-regulation of global gene expression, in Ni-transformed C3H/10T1/2 (10T1/2) mouse mouse embryo cell lines. His laboratory has shown that 150 genes are differentially expressed in 10T1/2 cell lines transformed by insoluble green NiO and crystalline NiS. In these transformed cell lines, the ect-2 proto-oncogene is amplified and over-expressed, and the Wdr1 stress gene and the calnexin gene are over-expressed. We also found that the DRIP80 gene and the beta-centaurin-2 gene have become quiescent in the Ni-transformed 10T1/2 cell lines. Our current working model is that 6 proto-oncogenes have become activated, and 9 tumor suppressor genes have become quiescent, in Ni-transformed 10T1/2 cell lines. Each alternation of these 15 primary genes leads to differential expression of 10 additional genes, indicating that there are substantial changes in regulation of gene expression in Ni-transformed 10T1/2 mouse embryo cell lines. Dr. Landolph’s laboratory has also studied the ability of insoluble nickel compounds and of soluble and insoluble Cr(VI) compounds to induce cytotoxicity and anchorage-independent transformation of cultured human diploid human fibroblasts. Dr. Landolph is an expert in chemically induced mutation and morphological/neoplastic transformation of mammalian cells. He has authored 65 scientific publications, given 204 invited scientific lectures, trained 105 B. S., 31 M. S., 5 Medical, and 14 Ph. D. students and 32 postdoctoral fellows, and hosted 10 faculty on sabbatical in his laboratory. He has reviewed grants for U. S. EPA, NIEHS, and Chemical Pathology/Al-Tox-4 Study Sections of NIH. He served as a member of: Carcinogen Identification Committee, Calif. EPA (1994-Present); Scientific Review Panel for Toxic Air Contaminants, Calif. Air Resources Board (2003-2011); Drinking Water (2003-2009), Human Health Research (2003), and STAA (2003-2006), Committees of U. S. EPA’s Science Advisory Board; U. S. EPA Board of Scientific Counselors’ Human Health Research Committee (2005-2006); and Natl. Acad. of Sciences Panel on U. S. EPA’s PCE Risk Assessment (2009-2010). He received the Merck Award in Chemistry (Drexel Univ.); ACS Postdoctoral Fellowship; and Edmundson Teaching Award (Dept. Path., USC). He has held research grants from EPA, NCI, and NIEHS.

Dr. Landolph has been a member of the Society of Toxicology from l985-Present. He received the ICI Traveling Lectureship Award from the Society of Toxicology in l990. He has served as a Member of the Graduate Student Awards Committee, Carcinogenesis Specialty Section, Society of Toxicology, from 1994-1999. He was elected Councilor, Carcinogenesis Specialty Section, Society of Toxicology, from 1997-1999. He was elected Vice-President Elect of the Metals Specialty Section for 1999-2000; Vice-President, Metals Specialty Section, 2000-2001; and President-Elect, Metals Specialty Section, 2001-2002. He also served as a Member of the Review Committee for Graduate Student/Postdoctoral Fellow Awards, 2000, Metals Specialty Section; Member of the Review Committee for Submissions to the SOT Program Committee from the Metals Specialty Section, 2002; President, Metals Specialty Section, 2002-2003; and Councilor, Metals Specialty Section, from 2003-2004. He was appointed a Member of the Regulatory Affairs and Legislative Assistance (RALA) Committee of the Society of Toxicology, from 2007-2010,

Awards

  • American Cancer Society, U. S. A. : American Cancer Society Postdoctoral Fellowship, l977-l979

Publications

  • Diabetes and cancer: epidemiological, clinical, and experimental perspectives Exp Diabetes Res. 2012; 2012:101802. . View in PubMed
  • XIII International Charles Heidelberger Symposium and 50 Years of Fluoropyrimidines in Cancer Therapy Held on september 6 to 8, 2007 at New York University Cancer Institute, Smilow Conference Center Mol Cancer Ther. 2009 May; 8(5):992-9. . View in PubMed
  • Amplification of the Ect2 proto-oncogene and over-expression of Ect2 mRNA and protein in nickel compound and methylcholanthrene-transformed 10T1/2 mouse fibroblast cell lines Toxicol Appl Pharmacol. 2005 Aug 07; 206(2):138-49. . View in PubMed
  • Human prostate cancer risk factors Cancer. 2004 Nov 15; 101(10 Suppl):2371-490. . View in PubMed
  • Molecular biology of nickel carcinogenesis: identification of differentially expressed genes in morphologically transformed C3H10T1/2 Cl 8 mouse embryo fibroblast cell lines induced by specific insoluble nickel compounds Mol Cell Biochem. 2004 Jan; 255(1-2):203-16. . View in PubMed
  • Genotoxicity of samples of nickel refinery dust Toxicol Sci. 2003 May; 73(1):114-23. . View in PubMed
  • Cell transformation assays as predictors of human carcinogenicity Altern Lab Anim. 1999 Sep-Oct; 27(5):745-67. . View in PubMed
  • Role of free radicals in metal-induced carcinogenesis Met Ions Biol Syst. 1999; 36:445-83. . View in PubMed
  • Molecular mechanisms of transformation of C3H/10T1/2 C1 8 mouse embryo cells and diploid human fibroblasts by carcinogenic metal compounds Environ Health Perspect. 1994 Sep; 102 Suppl 3:119-25. . View in PubMed
  • Induction of chromosomal aberrations, cytotoxicity, and morphological transformation in mammalian cells by the antiparasitic drug flubendazole and the antineoplastic drug harringtonine Fundam Appl Toxicol. 1994 Feb; 22(2):304-13. . View in PubMed
  • Role of valence state and solubility of chromium compounds on induction of cytotoxicity, mutagenesis, and anchorage independence in diploid human fibroblasts Cancer Res. 1990 Dec 15; 50(24):7835-42. . View in PubMed
  • Molecular and cellular mechanisms of transformation of C3H/10T1/2 Cl 8 and diploid human fibroblasts by unique carcinogenic, nonmutagenic metal compoundsA review. Biol Trace Elem Res. 1989 Jul-Sep; 21:459-67. . View in PubMed
  • Soluble vs insoluble hexavalent chromateRelationship of mutation to in vitro transformation and particle uptake. Biol Trace Elem Res. 1989 Jul-Sep; 21:469-74. . View in PubMed
  • Ouabain-resistant (Na+,K+)-ATPase enzyme activity in chemically induced ouabain-resistant C3H/10T1/2 cells Mol Toxicol. 1989 Apr-Jun; 2(2):75-98. . View in PubMed
  • Study of the ability of phenacetin, acetaminophen, and aspirin to induce cytotoxicity, mutation, and morphological transformation in C3H/10T1/2 clone 8 mouse embryo cells Cancer Res. 1989 Feb 15; 49(4):1038-44. . View in PubMed
  • Analgesics, cigarette smoking, and other risk factors for cancer of the renal pelvis and ureter Cancer Res. 1989 Feb 15; 49(4):1045-8. . View in PubMed
  • Morphological and neoplastic transformation of C3H/10T1/2 Cl 8 mouse embryo cells by insoluble carcinogenic nickel compounds Environ Mol Mutagen. 1989; 14(2):65-78. . View in PubMed
  • Transformation of C3H/10T1/2 mouse embryo cells to focus formation and anchorage independence by insoluble lead chromate but not soluble calcium chromate: relationship to mutagenesis and internalization of lead chromate particles Cancer Res. 1988 Sep 15; 48(18):5280-8. . View in PubMed
  • DT-diaphorase activity and the cytotoxicity of quinones in C3H/10T1/2 mouse embryo cells Biochem Pharmacol. 1988 Jun 15; 37(12):2451-9. . View in PubMed
  • Increased expression of the glucose-regulated gene encoding the Mr 78,000 glucose-regulated protein in chemically and radiation-transformed C3H 10T1/2 mouse embryo cells Cancer Res. 1987 Dec 01; 47(23):6220-4. . View in PubMed
  • Induction of anchorage independence in human diploid foreskin fibroblasts by carcinogenic metal salts Cancer Res. 1987 Jul 15; 47(14):3815-23. . View in PubMed
  • Enhanced expression and state of the c-myc oncogene in chemically and X-ray-transformed C3H/10T1/2 Cl 8 mouse embryo fibroblasts Cancer Res. 1987 Jul 15; 47(14):3643-9. . View in PubMed
  • Enhanced expression of c-myc and decreased expression of c-fos protooncogenes in chemically and radiation-transformed C3H/10T1/2 Cl 8 mouse embryo cell lines Cancer Res. 1986 Oct; 46(10):5302-11. . View in PubMed
  • In vitro genotoxicity studies using complex hydrophobic mixtures: efficient delivery of a petroleum sample to cultured C3H/10T1/2 cells via lipid vesicle incorporation Environ Mutagen. 1986; 8(4):589-609. . View in PubMed
  • Molecular analysis of several classes of endogenous feline leukemia virus elements J Virol. 1985 Dec; 56(3):701-10. . View in PubMed
  • Chemical transformation in C3H 10T1/2 Cl 8 mouse embryo fibroblasts: historical background, assessment of the transformation assay, and evolution and optimization of the transformation assay protocol IARC Sci Publ. 1985; 67:185-203. . View in PubMed
  • Cytotoxicity and negligible genotoxicity of borax and borax ores to cultured mammalian cells Am J Ind Med. 1985; 7(1):31-43. . View in PubMed
  • Mechanisms of chemically induced multistep neoplastic transformation in C3H 10T 1/2 cells Carcinog Compr Surv. 1985; 10:211-23. . View in PubMed
  • S-9 metabolic activation enhances aflatoxin-mediated transformation of C3H/10T1/2 cells Toxicol Appl Pharmacol. 1985 Jan; 77(1):58-65. . View in PubMed
  • Morphological correlates of transformation in cultured C3H/10T1/2 mouse embryo cells Carcinogenesis. 1984 Jul; 5(7):885-94. . View in PubMed
  • Microcell-mediated transfer of carcinogen-induced ouabain resistance from C3H/10T1/2 Cl 8 mouse fibroblasts to human cells Mutat Res. 1983 Feb; 107(2):447-63. . View in PubMed
  • Genetic and probability aspects of cell transformation by chemical carcinogens Prog Nucleic Acid Res Mol Biol. 1983; 29:87-98. . View in PubMed
  • Induction of ouabain-resistant mutants by chemical carcinogens in rat prostate epithelial cells Environ Mutagen. 1983; 5(1):33-48. . View in PubMed
  • Induction of cytotoxicity, mutation, cytogenetic changes, and neoplastic transformation by benzo(a)pyrene and derivatives in C3H/10T1/2 clone 8 mouse fibroblasts Cancer Res. 1982 May; 42(5):1866-75. . View in PubMed
  • Mutagenicity of 5-azacytidine and related nucleosides in C3H/10T 1/2 clone 8 and V79 cells Cancer Res. 1982 Mar; 42(3):817-23. . View in PubMed
  • Oncogenic transformation and mutation of C3H/10T 1/2 clone 8 mouse embryo fibroblasts by alkylating agents Cancer Res. 1981 Aug; 41(8):3095-9. . View in PubMed
  • Comparison of adriamycin- and ouabain-induced cytotoxicity and inhibition of 86rubidium transport in wild-type and ouabain-resistant C3H/10T1/2 mouse fibroblasts Cancer Res. 1980 Dec; 40(12):4581-8. . View in PubMed
  • Further evidence that ouabain-resistant variants induced by chemical carcinogens in transformable C3H/10T1/2 Cl 8 mouse fibroblasts are mutants Mutat Res. 1980 Sep; 72(2):295-310. . View in PubMed
  • Modulation of the cell cycle of cultured mouse liver cells by benzo(a)pyrene and its derivatives Cancer Res. 1979 Jul; 39(7 Pt 1):2538-43. . View in PubMed
  • Chemical carcinogens produce mutations to ouabain resistance in transformable C3H/10T1/2 Cl 8 mouse fibroblasts Proc Natl Acad Sci U S A. 1979 Feb; 76(2):930-4. . View in PubMed
  • Biochemical basis for the acquisition of resistance to benzo[a]pyrene in clones of mouse liver cells in culture Chem Biol Interact. 1978 Dec; 23(3):331-44. . View in PubMed
  • Mutagenesis of Chinese hamster cells is facilitated by thymidine and deoxycytidine Nature. 1978 Nov 30; 276(5687):508-10. . View in PubMed
  • Quantitative studies of the toxicity of benzo(a)pyrene to a mouse liver epithelial cell strain in culture Cancer Res. 1976 Nov; 36(11 Pt 1):4143-51. . View in PubMed