Alvaro Puga

Professor

Division: Toxicology

E-Mail: PUGAA@UCMAIL.UC.EDU
Phone: 513-558-0916
Location: 424 Kettering Lab
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Alvaro Puga

My laboratory investigates the impact of genetic diversity on the response of individuals or populations to toxic or carcinogenic environmental agents. The long-term objective of this work is to elucidate the molecular mechanisms that underlie this response. Many chemical compounds interfere with the control mechanisms that regulate gene expression, and some compounds may induce overexpression of target genes, while others may repress their normal expression levels. The ultimate effect of this process isan alteration of the steady-state levels of the proteins encoded by the genes affected. In recent years, however, it has become increasingly clear that this effect varies drastically as a result of genetic differences in the individuals affected. My interests are centered, on the one hand, on the molecular mechanisms of action of these toxic environmental agents, and on the other, on the analysis of genetic diversity in the response to these agents. The genes of interest are those that code for transcription factors with a regulatory role in the expression of detoxification enzymes. Our work centers on the molecular mechanisms of action of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, or TCDD), a ligand for the aromatic hydrocarbon (Ah) receptor, that functions as a transcriptional activator of the cytochrome P450 CYP1A1 gene. The CYP1A1 enzyme is responsible for the metabolic activation of many polycyclic aromatic hydrocarbon procarcinogens to ultimate carcinogens. In mice, and possibly in humans, allelic differences at the genetic locus for the Ah receptor are responsible for differences in ligand affinity, gene inducibility and ultimately, cancer incidence. We are therefore also analyzing structure/function relationships of variant forms of the gene coding for the Ah receptor protein.

Related News:

  • 02/12/2015: With $2.4M Grant, Researchers to Collaborate in Study of Heart Disease
  • 01/23/2013: Alvaro Puga Accepted as ATS Fellow
  • 11/29/2012: Two from Academic Health Center Named AAAS Fellows
  • 06/01/2009: Research Finds Novel Roles for AHR in Development

  • Education

    Universidad Complutense, Madrid, Spain, Licenciate 1966

    Purdue University, W. Lafayette, Indiana, Ph.D. 1972

    Scripps Clinic & Research Foundation, La Jolla, California, Postdoctoral Fellow 1976

    Awards

    1966-1967 Fellow, Wallenberg Foundation for Cultural Exchange. Institute of Genetics. Lund,Sweden.

    1967-1968 Fellow, Fulbright-Hayes International Exchange Program. Purdue University. Lafayette,IN.

    1968-1972 Fellow, David Rose Foundation. Dept. of Biological Sciences, Purdue University. Lafayette,IN.

    1999 Society of Toxicology Lectureship Award

    2002 University of Cincinnati College of Medicine Richard Akeson Award for Excellence in Teaching.

    Professional Experience

    1965 – 1967 Teaching Assistant, Departamento de Genética. Facultad de Ciencias Biológicas. Universidad Complutense de Madrid, Spain.

    1967 – Guest Worker, Laboratory of Molecular Cytogenetics. Institute of Genetics. University of Lund. Sweden.

    1967 – 1970 Graduate Research Assistant, Department of Biological Sciences. Purdue University, West Lafayette, Indiana.

    1970 – 1972 Graduate Research Associate, Department of Molecular Biology and Biochemistry. University of California, Irvine, California.

    1972 – Postdoctoral Fellow, Department of Molecular Biology and Biochemistry. University of California, Irvine, California.

    1972 – 1976 Postdoctoral Research Fellow, Department of Immunopathology. Scripps Clinic and Research Foundation. La Jolla, California.

    1976 – 1982 Senior Staff Fellow, Laboratory of Oral Medicine. NIDR, NIH. Bethesda, Maryland.

    1982 – 1987 Expert, Laboratory of Oral Medicine. NIDR, NIH. Bethesda, Maryland.

    1987 – 1991 Expert, Laboratory of Developmental Pharmacology. NICHHD, NIH. Bethesda, Maryland.

    1988 – 1991 Head, Unit on Pharmacogenetics, Laboratory of Developmental Pharmacology. NICHHD, NIH. Bethesda, Maryland.

    1989 – 1991 Deputy Chief, Laboratory of Developmental Pharmacology. NICHHD, NIH. Bethesda, Maryland.

    1991 – 1994 Research Associate Professor, Department of Environmental Health. University of Cincinnati College of Medicine. Cincinnati, Ohio.

    1994 – 1999 Associate Professor (tenured), Department of Environmental Health. University of Cincinnati College of Medicine. Cincinnati, Ohio.

    1994 – 1999 Associate Professor (secondary appointment), Department of Cell Biology, Neurobiology and Anatomy. University of Cincinnati College of Medicine. Cincinnati, Ohio.

    1999 – Professor, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio.

    2000- Professor, (secondary appointment), Department of Cell and Cancer Biology. University of Cincinnati College of Medicine. Cincinnati, Ohio.

    ADMINISTRATION

    1992 – 1995 NIEHS Center for Environmental Genetics; Head, Molecular Biology Service Core.

    1996 – 2005 NIEHS Center for Environmental Genetics; Head, Signal Transduction Research Core.

    1997 – Prsnt NIEHS Center for Environmental Genetics; Internal Advisory Committee.

    1998 – 2004 University of Cincinnati DNA Advisory Committee, Functional Genomics Subcommittee.

    1998 – Prsnt Associate Director, Mutagenesis and Carcinogenesis Training Grant

    1999 – 2004. University of Cincinnati Genomics, Proteomics and Bioinformatics Steering Committee.

    1999 – 2003 Director, U. Cincinnati Howard Hughes Medical Institute Functional Genomics Core.

    2004 – Prsnt Deputy Director, University of Cincinnati Superfund Basic Research Program

    2005 – 2007 Director, NIEHS Center for Environmental Genetics

    2007 – Prsnt Deputy Director, NIEHS Center for Environmental Genetics

    SERVICE

    Department of Environmental Health

    1993 – 1994 Environmental Health Library Committee

    1993 – 1995 Graduate Students Admission Committee

    1993 – 1995 Examiner, Departmental Foreign Language (Spanish) Requirement

    1995 – 1996 Chair, Postdoctoral Fellows Recruitment Committee

    1997 – 1999 Member, Appointments, Reappointments, Promotions and Tenure Committee

    1998 – 2000 Member, Signal Transduction Faculty Search Committee

    1998 – 2001 Member, Search Committee, Robert Kehoe Chair in Environmental Health

    2001 – 2003 Member, Appointments, Reappointments, Promotions and Tenure Committee

    2004 – 2005 Member, Search Committee, Director, Department of Environmental Health

    2006 – Prsnt Member, Bioinformatics Faculty Search Committee

    College of Medicine

    1996 – 1998 Member, Advisory Committee on English Language Examinations for Foreign Students

    1997 – 2000 Physician Scientist Training Program (MD/PhD) Recruitment Committee

    2001 – 2006 Postdoctoral Forum Award Committee

    2004 – 2006 Member, Advisory Committee to Re-structure the Core Curriculum

    2006 – Prsnt Member, Infrastructure Committee, UC. College of Medicine

    University Hospital

    1991 – Pres. Volunteer Spanish-English Interpreter

    University

    Member, Graduate Faculty

    Fellow of the Graduate School

    INSTITUTIONAL, NATIONAL AND INTERNATIONAL COMMITTEES SERVED

    1978 Member, Institutional Recombinant DNA Subcommittee, NIH, Bethesda, Maryland.

    1985 Member, NIAID IRG on Program Project Proposals on Mechanisms of Herpesvirus Latency.

    1993 Member, NCI Special Emphasis Panel: Biotechnology Transfer to Epidemiologic Studies in Cancer.

    1993 Member, NCI Special Emphasis Panel: Interdisciplinary Collaborative Studies in the Genetic Epidemiology of Cancer.

    1995 Chairperson, VII International Congress of Toxicology Continuing Education Program in Molecular Biology in Toxicology, Seattle, Washington.

    1996 Session Chairperson. Society of Toxicology Annual Meeting. Anaheim, California.

    1997 Session Chairperson. Society of Toxicology Annual Meeting. Cincinnati, Ohio.

    1997 Member, NIEHS Special Emphasis Panel: Growth Factors and Signal Transduction Pathways in Environmentally-Induced Disease.

    1998 Session Chairperson. Society of Toxicology Annual Meeting. Seattle, Washington.

    1998 Session Chairperson. 1st International Colloquium on Transcription Factors. Luxembourg.

    1999 Session Chairperson. 2nd International Colloquium on Candidate Susceptibility Genes for Cardiovascular Disease. Nancy, France.

    1999 Ad Hoc Member. NIH ALTX-1 Study Section.

    1999 Panel Member, Epidemiology. U.S. Army Breast Cancer Research Program.

    2000 Session Chairperson. International Symposium on Signal Transduction Pathways. Luxembourg.

    2000 Councillor, Molecular Biology Specialty Section, Society of Toxicology.

    2000 Member, Program Committee, Society of Toxicology.

    2000 Member, Organizing Committee, 6th Biological Reactive Intermediates Symposium, Paris.

    2001 Member, NIH ALTX-1 Study Section.

    2001 Member, Program Committee, Society of Toxicology.

    2001 Session Chairperson. Society of Toxicology Annual Meeting. San Francisco, California.

    2001 Senior Councillor, Molecular Biology Specialty Section, Society of Toxicology.

    2002 Session Chairperson. International Symposium on Cell Signaling, Transcription and Translation as Therapeutic Targets. Luxembourg.

    2002 Member, Program Committee, Society of Toxicology

    2002 Session Chairperson. Society of Toxicology Annual Meeting. Nashville, Tenesee.

    2002 Session Chairperson, 22nd International Symposium on Halogenated Environmental Organic Pollutants. Barcelona, Spain.

    2003 Member, Membership Committee, Society of Toxicology

    2003 Chairperson, ALTX-1 Study Section

    2004 Member, XNDA Study Section

    2004 Session Chairperson, International Symposium on Chromatin Structure and Gene Expression. Luxembourg.

    2004 Member, National Academy of Sciences Committee on Assessment of the Health Implications of Exposure to Dioxin.

    2005 Session Chairperson. Sixth Düsseldorf Symposium in Immunotoxicology Düsseldorf, Germany.

    2006 Session Chairperson. Society of Toxicology Annual Meeting. San Diego, California.

    2006 Chair, Special Emphasis Panel Study Section on RFA on Interdisciplinary Partnerships in Environmental Health Sciences, Research Triangle Park, NC.

    2008 Keynote Speaker. 2nd Toxicogenomics Symposium, Fudan Univ. Shanghai. P.R. China.

    2008 Member, Study Section to review the ONES Awards, NIEHS. February 2008.

    2008 Member, Institute of Medicine Committee to Evaluate the Health Effects of Agent Orange

    2008 Chair, 11th International Seminar on New Trends in Chemical Toxicology, Moscow, Russia

    Grants

    5-R01-ES-00627309/30/2004-06/30/2010. National Institute of Environmental Health Sciences. Molecular Mechanisms of Dioxin Action, PI, Closed.

    2 R01 ES01080701/01/2006-02/28/2011. National Institute of Environmental Health Sciences. Molecular Mechanisms of Complex Mixture Toxicity, PI, Closed.

    HE-WSU-00-15-01-A0-S0-E007/01/2000-06/30/2003. Ohio Board of Regents. DNA Microarray Approaches to Toxicology Testing, PI, Closed.

    5-R01-ES-010807-05-A0-S0-E001/16/2001-12/31/2005. National Institute of Environmental Health Sciences. Molecular Mechanisms of Complex Mixture Toxicity, PI, Closed.

    PMERP-03-A0-S0-E006/01/2001-11/30/2004. Philip Morris External Research Program. Molecular Markers of Benzo[a]pyrene-Induced Atherosclerosis, PI, Closed.

    5-R01-ES-06273-05-A0-S0-E009/30/1993-08/31/1999. National Institute of Environmental Health Sciences. Molecular Mechanisms of Dioxin Action, PI, Closed.

    5-R01-ES-006273-09-A0-S0-E005/01/1999-04/30/2004. National Institute of Environmental Health Sciences. Molecular Mechanisms of Dioxin Action, PI, Closed.

    P30 ES006096-16A104/01/2008-03/31/2013. National Institute of Environmental Health Sciences. Environmental Genetics, Collaborator, Active.

    R01 EY01522706/01/2009-05/31/2014. National Eye Institute. The Role of MAP 3 Kinase 1 in Ocular Surface Morphogenesis, Collaborator, Active.

    R56 ES00627309/01/2009-08/31/2011. National Institute of Environmental Health Sciences. Molecular Mechanisms of Dioxin Action, PI, Closed.

    R01 ES01080701/06/2011-12/31/2015. National Institute of Environmental Health Sciences. Molecular Mechanisms of Complex Mixture Toxicity, PI, Active.

    R01 ES00627304/01/2011-01/31/2016. National Institute of Environmental Health Sciences. Molecular Mechanisms of Dioxin Action, PI, Active.

    R21 ES02004806/09/2011-05/31/2013. National Institute of Environmental Health Sciences. Epigenetics of Lead Toxicity in Mouse Brain, PI, Active.

    P30ES00609604/01/2013-03/31/2018. National Institute of Environmental Health Sciences. Environmental Genetics, Collaborator, Active.

    R21ES02331908/29/2013-07/31/2016. National Institute of Environmental Health Sciences. Transgenerational Inheritance of Epigenetic Effects of Polychlorinated Biphenyls, PI, Awarded.

    T32 ES01664607/01/2008-06/30/2014. National Institute of Environmental Health Sciences. Gene-Environment Interaction Training Program, PI, Active.

    1 R01 ES024744-0111/10/2014-10/31/2019. National Institute of Environmental Health Sciences. Gene-Environment Interactions in the Fetal Origin of Adult Cardiac Disease, PI, Awarded.

    R01 EY015227-10A112/01/2014-11/30/2019. National Eye Institute. The Role of MAP 3 Kinase 1 in Ocular Surface Morphogenesis, Collaborator, Active.

    Selected Publications

    01. Vasunia, K. B., Miller, M. L., Puga, A., and Baxter, C. S. Granulocyte-macrophage colony-stimulating factor is expressed in mouse skin in response to tumor-promoting agents and modulates dermal inflammation and epidermal dark cell numbers. Carcinogenesis 15:653-660 (1994).

    02. Liu, R.-M., Vasiliou, V., Zhu, H., Duh, J.-L., Tabor, W. M., Puga, A., Nebert, D. W., Sainsbury, M., and Shertzer, H. G. Regulation of Ah gene battery enzymes and glutathione levels by 5,10-dihydroindeno[1,2,-b]indole in mouse hepatoma cell lines. Carcinogenesis 15:2347-2352 (1994).

    03. Carrier, F., Chang, C.-Y., Duh, J.-L., Nebert, D.W., and Puga, A. Interaction of the regulatory domains of the murine Cyp1a1 gene with two DNA-binding proteins in addition to the Ah receptor and the Ah receptor nuclear translocator (ARNT). Biochem. Pharmacol.48:1767-1778 (1994).

    04. Vasiliou, V., Theurer, M.J., Puga, A., Reuter, S.F., and Nebert, D.W. Mouse dioxin-inducible NAD(P)H:menadione oxidoreductase: NMO1 cDNA sequence and genetic differences in mRNA levels. Pharmacogenetics 4:341-348 (1994).

    05. Yao, Y., Hoffer, A., Chang, C.-Y., and Puga, A. Dioxin activates HIV-1 gene expression by an oxidative stress pathway that requires a functional cytochrome P450 CYP1A1 enzyme. Environmental Health Persp. 103:366-371 (1995).

    06. Vasiliou, V., Puga, A., Chang, C.-Y.,Tabor, M. W., and Nebert, D.W. Interaction between the Ah receptor and proteins binding to the AP-1-like electrophile response element (EpRE) during murine phase II [Ah] battery gene expression. Biochem. Pharmacol. 50:2057-2068 (1995).

    07. Duh, J.-L., Zhu, H., Shertzer, H.O., Nebert, D.W., and Puga, A. The Y-box motif mediates redox-dependent transcriptional activation in mouse cells. J. Biol. Chem. 270:30499-30508 (1995).

    08. Liang, H.-C. L., Li, H., McKinnon, R.A., Duffy, J.J., Potter, S. S., Puga, A., and Nebert, D.W. Cyp1a2(-/-) null mutant mice develop normally, but show deficient drug metabolism. Proc. Nat. Acad. Sci. USA, 93:1671-1676 (1996).

    09. Nebert, D.W., McKinnon, R., and Puga, A. Human drug-metabolizing enzyme polymorphisms: effects on risk of toxicity and cancer. DNA and Cell Biol. 15:273-280 (1996).

    10. FitzGerald, C. T., Fernandez-Salguero, P., Gonzalez, F. J., Nebert, D.W., and Puga, A. Differential regulation of mouse Ah receptor gene expression in cell lines of different tissue origins. Arch. Biochem. Biophys. 333:170-178 (1996).

    11. Hoffer, A., Chang, C.-Y. and Puga, A. Dioxin induces fos and jun gene expression by Ah receptor-dependent and -independent pathways. Toxicol. Appl. Pharmacol. 141: 238-147 (1996).

    12. Puga, A., Nebert, D.W., McKinnon,R.A. and Menon, A.G. Genetic polymorphisms in human drug-metabolizing enzymes: potential uses of reverse genetics to identify genes of toxicological relevance. Crit. Rev. Toxicol. 27:199-222 (1997).

    13. Micka, J., Milatovich, A., Menon, A., Grabowski, G., Puga, A. And Nebert, D.W. Human Ah receptor (AHR) gene: localization to 7p15 and suggestive correlation of polymorphism with CYP1A1 inducibility. Pharmacogenetics 7:95-101 (1997).

    14. Puga, A., Hoffer, A., Zhou, S., Bohm, J.M., Leikauf, G.D. and Shertzer, H.G. Sustained increase in intracellular free calcium and activation of COX-2 expression in mouse hepatoma cells treated with dioxin. Biochem. Pharmacol. 54:1287-1296 (1997).

    15. Chang, C.-Y. and Puga, A. Constitutive activation of the aromatic hydrocarbon receptor. Mol.Cell.Biol. 18:525-535 (1998).

    16. Maier, A., Micka, J., Miller, K., Denko, T., Chang, C.-Y., Nebert, D.W. and Puga, A. Aromatic hydrocarbon receptor (AHR) polymorphism: development of new methods to correlate genotype with phenotype. Environ. Health Persp. 106:421-426 (1998).

    17. FitzGerald, C.T., Nebert, D.W. and Puga, A. Regulation of mouse Ah receptor gene expression by members of the Sp family of transcription factors. DNA and Cell Biol. 17:811-822 (1998).

    18. Shertzer, H.G., Nebert, D.W., Puga, A. Ary, M., Sonntag, D., Dixon, K., Robinson, L.J., Cianciolo E., and Dalton, T.P. TCDD causes a sustained oxidative stress response in C57BL/6J mice. Biochem. Biophys. Res. Commun. 253:44-48 (1998).

    19. Shertzer, H.G., Puga, A., Chang, C.-Y., Smith, P., Nebert, D.W., Setchell, K.D.R., and Dalton, T.P. Inhibition of CYP1A1 enzyme activity in mouse hepatoma culture by soybean isoflavones. Chem.-Biol. Interact. 123:31-49 (1999).

    20. Vasilou, V. Reuter, S.F., Williams, S., Puga, A., and Nebert, D.W. Mouse cytosolic class 3 aldehyde dehydrogenase (Aldh3a1): gene structure and regulation of constitutive and dioxin-inducible expression. Pharmacogenetics 9:569-580 (1999).

    21. Puga, A., Barnes, S.J., Dalton, T.P., Chang, C.-Y., Knudsen, E.S. and Maier, A. Aromatic hydrocarbon receptor interaction with the retinoblastoma Protein potentiates Repression of E2F-Dependent Transcription and Cell Cycle Arrest. J. Biol. Chem. 275:2943-2950 (2000).

    22. Puga, A., Barnes, S.J., Chang, C.-Y., Zhu,H., Nephew,K.P., Khan, S.A., and Shertzer, H.G. Activation of transcription factors AP-1 and NF-B by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochem. Pharmacol. 59:997-1005 (2000).

    23. Strobeck, M., Puga, A., and Knudsen, E. Restoration of retinoblastoma mediated signaling to cdk2 results in cell cycle arrest. Oncogene 19:1857-1867 (2000).

    24. Maier, A., Dalton, T.P. and Puga, A. Pro-oxidant metals disrupt the coordinate induction of phase I and phase II detoxification genes by dioxin. Mol. Carcinogenesis. 28:225-235 (2000).

    25. Puga, A., Maier, A. and Medvedovic, M. The transcritional signature of dioxin in human hepatoma HepG2 cells. Biochem. Pharmacol. 60:1129-1142 (2000).

    26. Diederich, M., Borde-Chiche, P., Morceau, F., Puga, A., Wellman, M. and Dicato, M. Methylation of the minimal promoter of the glutathione S-trasferase P gene silences transcription in human leukemia cells. Biochem. Pharmacol. 61(5):605-612 (2001).

    27. Dalton, T.P., Kerzee, J.K., Wang, B., Miller, M., Dieter, M.Z., Lorenz, J.N., Howard G. Shertzer,H.G., and Puga, A. Dioxin Exposure is an Environmental Risk Factor for the Development of Atherosclerosis. Cardiovasc. Toxicol. 1:285-298 (2001).

    28. Maier, A., Schumann, B.L., Chang, X., Talaska, G., and Puga, A. Arsenic coexposure potentiates benzo[a]pyrene genotoxicity. Mutat. Res. 517:101-111 (2002).

    29. Tan, Z., Chang, X., Puga, A.and Xia, Y. Ah receptor ligands induce MAP kinases needed for receptor activity. Biochem. Pharmacol. Biochem. Pharmacol. 64:771-780 (2002).

    30. Wetherill, Y.B., Petre, C.E., Puga, A., and Knudsen, K.E. The xenoestrogen bisphenol A induces inappropriate androgen receptor activation and mitogenesis in prostatic adenocarcinoma cells. Mol. Cancer Therap. 1:515-524 (2002).

    31. Dalton, T.P., Puga, A. and Shertzer, H.G. Role of the Ah receptor in oxidative stress. Chem. Biol. Interact. 141:77-95 (2002).

    32. Puga, A. Xia, Y., and Elferink, C. Role of the Ah receptor in cell cycle regulation. Chem. Biol. Interact 141:117-130 (2002).

    33. Kerzee, J.K. and Puga, A. Global gene expression profiling of aryl hydrocarbon receptor ligands. In: Genomic and Proteomic Applications in Toxicity Testing (M.J. Cunningham, editor). Humana Press. In press (2003).

    34. Kerzee, J.K., Xia, Y., and Puga, A. Biochemical Responses to Dioxin: Which Genes? Which Endpoints? In, Dioxins: Toxicology, Mechanisms and Health Implications, 2nd edition. A. Schecter and T. Gasiewicz, eds. In press (2003).

    35. Puga, A., Marlowe, J., Barnes, S., Chang, C.-Y., Maier, A., Tan, Z., Kerzee, J.K., Chang, X., Strobeck, M. W. and Knudsen, E.S. Role of the aryl hydrocarbon receptor in cell cycle regulation. Toxicology 181-182:171-177 (2002).

    36. Vonderheide, A.P., Meija, J., Tepperman, K., Puga, A., Pinhas, A.R., States, J.C., and Caruso, J.A. Retention of Cr(III) by high performance chelation ion chromatography interfaced to inductively coupled plasma mass spectrometric detection with collision cell. J. Chromatography A, 1024:129-137 (2004).

    37. Guo, J., Sartor, M. Karyala, S., Medvedovic, M. Kann, S., Puga, A., Ryan, P. and Tomlinson, C. Expression of genes in the TGF-beta signaling pathway is significantly deregulated in smooth muscle cells from aorta of aryl hydrocarbon receptor knockout mice. Toxicol. and Appl. Pharmacol. 194:79-89 (2004).

    38. Wei, Y.-D., Tepperman, K., Sartor, M.A. and Puga, A. Chromium inhibits transcription from PAH inducible promoters by blocking the release of HDAC and preventing the binding of p300 to chromatin. J. Biol. Chem.:279:4110-4119 (2004).

    39. Karyala, S., Guo, J., Sartor, M., Medvedovic, M., Kann, S., Puga, A., Ryan, P., and Tomlinson, C.R. Different global gene expression profiles in B[a]P and TCDD treated vascular smooth muscle cells of AHR knockout and wild type mice. Cardiovascular Toxicol. 4: 47-74 (2004).

    40. Singleton, D.W., Feng, Y., Chen, Y., Busch, S.J., Lee, A.V., Puga, A. And Khan, S.A. Bisphenol-A and Estradiol Exert Novel Gene Regulation In Human MCF-7 Derived Breast Cancer Cells. Mol. Cell. Endocrinol. 221:47-55. (2004).

    41. Marlowe, J.,Knudsen, E.S., Schwemberger and Puga, A. The aryl hydrocarbon receptor displaces p300 from E2F-dependent promoters and represses S-phase specific gene expression. J. Biol. Chem. 279:29013-29022. (2004).

    42. Puga, A., Sartor, M., Huang, M.-Y., Kerzee, J.K., Wei, Y.D., Tomlinson, C.R. and Medvedovic. M. Gene expression profiles of cultured vascular smooth muscle cells and mouse aorta are widely different, but show common responses to dioxin exposure. Cardiovascular Toxicol. 4:385-403 (2004).

    43. Barnes-Ellerbe, S., Knudsen, E.S. and Puga, A. TCDD blocks androgen-dependent proliferation of LNCaP cells through modulation of RB phosphorylation. Mol. Pharmacol. 66:502-511 (2004).

    44. Tan, Z., Huang, M., Puga, A. and Xia, Y. A critical role for MAP kinases in the control of Ah receptor complex activity. Toxicol. Sci. 82:80-87 (2004).

    45. Puga, A., Tomlinson, C.R. and Xia, Y. Aryl hydrocarbon receptor signals cross-talk with multiple developmental pathways. Biochem. Pharmacol. 69:199-207 (2005).

    46. Kann, S., Estes, C., Reichard, J.F., Huang, M.-Y., Sartor, M.A., Schwemberger, S., Chen, Y., Dalton, T.P., Shertzer, H.G., Xia, Y. and Puga, A. Butylhydroquinone protects cells genetically deficient in glutathione biosynthesis from arsenite induced apoptosis without significantly changing their prooxidant status. Toxicol. Sci. 87:365-384 (2005).

    47. Kann, S., Huang, M.Y., Estes, C., Reichard, R.F., Sartor, M.A., Xia, Y. and Puga, A. Arsenite induced aryl hydrocarbon receptor nuclear translocation results in additive induction of phase I and synergistic induction of phase II genes. Mol. Pharmacol. 68:336-346 (2005).

    48. Marlowe, J.L. and Puga, A. Ah receptor, cell cycle, toxicity and tumorigenesis. J. Cell. Biochem. 96:1174-1184 (2005).

    49. Singleton, D.W., Feng, Y., Yang, J., Puga, A., Lee, A.V. and Khan, S.A. Gene expression profiling reveals novel regulation by bisphenol A in estrogen receptor alpha positive human cells. Environ. Res. 10:86-92 (2006).

    50. Talaska, G., Ginsburg, D., Ladow, K., Puga, A., Dalton, T. and Warshawsky, D. Impact of Cyp1a2 or Ahr geout in mice: Implications for biomonitoring studies. Toxicol Lett. 162:246-249 (2006).

    51. Genter, M.B., Marlowe, J., Kerzee, K.J., Dragin, N., Puga, A., Dalton, T.P., Nebert, D.W.Naphthalene toxicity in mice and aryl hydrocarbon receptor mediated CYPs. Biochem. Biophys. Res. Commun. 348:120 3 (2006).

    52. Reichard, J.F., Schnekenburger, M. and Puga, A. Long term low-dose arsenic exposure induces loss of DNA methylation. Biochem. Biophys. Res. Comm. 352:188 192. (2007).

    53. Chang, X., Fan, Y., Karyala, S., Schwemberger, S., Tomlinson, C.R., Sartor, M.A. and Puga, A. Ligand independent regulation of transforming growth factor 1 expression and cell cycle progression by the aryl hydrocarbon receptor. Mol. Cell. Biol. 27: 6127-6139 (2007).

    54. Schnekenburger, M., Peng, L. and Puga, A. HDAC1 bound to the Cyp1a1 promoter blocks histone acetylation required for transactivation by the Ah receptor. Biochim. Biophys. Acta 1769:569-578 (2007).

    55. Reichard, J. Goetz, G. and Puga, A. Heme oxygenase 1 induction by Nrf2 requires inactivation of the transcriptional repressor BACH1. Nucleic Acids Res. 35:7074-7086 (2007).

    56. Schnekenburger, M., Talaska, G. and Puga, A. Chromium cross-links HDAC1∙DNMT1 complexes to chromatin inhibiting histone remodeling marks critical for transcriptional activation. Mol. Cell. Biol. 27:7089-7101 (2007).

    57. Puga, A., Xia, Y., Tan,Z., Chang, X. and Schnekenburger, M. The aryl hydrocarbon receptor cross-talks with multiple signal transduction pathways. Proceedings of the 27th International Symposium on Organohalogenated Compounds, 69:616-620 (2007).

    58. Peng, L., Mayhew, C.N., Schnekenburger, M., Knudsen, E.S. and Puga, A. Repression of Ah receptor and induction of transforming growth factor- genes in DEN-induced mouse liver tumors. Toxicology 246:242-247 (2008).

    59. Puga, A., Wei, Y.-D., Maier, A., Peng, L. And Schnekenburger, M. Reprogramming of histone marks by chromium. Cell Biol. Toxicol. In press (2008).

    60. Gómez-Durán, A., Ballestar, E., Marlowe J.L., Puga, A., Esteller, M. and Fernández-Salguero, P.M. Recruitment of CREB1 and histone deacetylase 2 (HDAC2) to the mouse Ltbp1 promoter regulates its constitutive expression in a dioxin receptor-dependent manner. J. Mol. Biol. 380:1-16 (2008).

    61. Marlowe, J.L., Fan, Y., Chang, X., Peng, L., Knudsen, E.S., Xia, Y. and Puga, A. The Ah receptor binds to E2F1 and inhibits E2F1-induced apoptosis. Mol. Biol. Cell. 19: 3263-3271(2008).

    62. Reichard, J.F., Sartor, M.A. and Puga, A. BACH1 is a specific repressor of HMOX1 that is inactivated by arsenite. J. Biol. Chem. 283:22363-22370 (2008).

    63. Puga, A., Ma, C. and Marlowe, J.L. The aryl hydrocarbon receptor cross-talks with multiple signal transduction pathways. Biochem. Pharmacol. (2008). Sept 5 Epub ahead of print.

    64. Gomez-Duran, A., Carvajal-Gonzalez, J.M., Mulero-Navarro, S., Santiago-Josefat, B., Puga, A. and Fernandez-Salguero, P.M. Fitting a xenobiotic receptor into cell homeostasis: How the dioxin receptor interacts with TGFβ signaling. Biochem. Pharmacol. (2008). Sept 5 Epub ahead of print.

    66. Kroening, K.K., Solivio, M.J.V., García-Lopez, M., Puga, A. and Caruso, J.A. Cytotoxicity of arsenic containing chemical warfare agent degradation products with metallomic approaches for metabolite analysis. Metallomics, in press (2008).