Thomas Gasiewicz

Summary

Affiliation: University of Rochester
Country: USA

Publications

  1. pmc The aryl hydrocarbon receptor has a normal function in the regulation of hematopoietic and other stem/progenitor cell populations
    Kameshwar P Singh
    Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA
    Biochem Pharmacol 77:577-87. 2009
  2. pmc TCDD and a putative endogenous AhR ligand, ITE, elicit the same immediate changes in gene expression in mouse lung fibroblasts
    Ellen C Henry
    Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA
    Toxicol Sci 114:90-100. 2010
  3. pmc The aryl hydrocarbon receptor has an important role in the regulation of hematopoiesis: implications for benzene-induced hematopoietic toxicity
    Thomas A Gasiewicz
    Department of Environmental Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Chem Biol Interact 184:246-51. 2010
  4. ncbi request reprint The aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin alters the circadian rhythms, quiescence, and expression of clock genes in murine hematopoietic stem and progenitor cells
    Russell W Garrett
    Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester Medical Center, 601 Elmwood Avenue, Box EHSC, Rochester, NY 14642, USA
    Mol Pharmacol 69:2076-83. 2006
  5. ncbi request reprint 2,3,7,8-tetrachlorodibenzo-p-dioxin does not directly alter the phenotype of maturing B cells in a murine coculture system
    Amber Wyman
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    Toxicol Appl Pharmacol 180:164-77. 2002
  6. pmc Treatment of mice with the Ah receptor agonist and human carcinogen dioxin results in altered numbers and function of hematopoietic stem cells
    Kameshwar P Singh
    Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA
    Carcinogenesis 30:11-9. 2009
  7. pmc The aryl hydrocarbon receptor attenuates tobacco smoke-induced cyclooxygenase-2 and prostaglandin production in lung fibroblasts through regulation of the NF-kappaB family member RelB
    Carolyn J Baglole
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 283:28944-57. 2008
  8. ncbi request reprint TCDD-induced alterations in gene expression profiles of the developing mouse paw do not influence morphological differentiation of this potential target tissue
    Jeffrey C Bemis
    Department of Environmental Medicine, Rochester, New York 14642, USA
    Toxicol Sci 95:240-8. 2007
  9. ncbi request reprint Epigallocatechin gallate inhibits aryl hydrocarbon receptor gene transcription through an indirect mechanism involving binding to a 90 kDa heat shock protein
    Christine M Palermo
    Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA
    Biochemistry 44:5041-52. 2005
  10. ncbi request reprint Aryl hydrocarbon receptor expression and activity in cerebellar granule neuroblasts: implications for development and dioxin neurotoxicity
    Mary A Williamson
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    Toxicol Sci 83:340-8. 2005

Research Grants

  1. Ah Receptor Dysregulation Alters Hematopoietic Stem Cells
    Thomas A Gasiewicz; Fiscal Year: 2011
  2. EFFECT OF TCDD ON T LYMPHOCYTE DIFFERENTIATION
    Thomas Gasiewicz; Fiscal Year: 2002
  3. DEVELOPMENTAL ACTIVITY OF AH RECEPTOR IN VIVO
    Thomas Gasiewicz; Fiscal Year: 2001
  4. Developmental Activity of the Ah Receptor
    Thomas Gasiewicz; Fiscal Year: 2005
  5. Ah Receptor Dysregulation Alters Hematopoietic Stem Cells
    Thomas A Gasiewicz; Fiscal Year: 2010
  6. Effects of TCDD on T Lymphocyte Differentiation
    Thomas Gasiewicz; Fiscal Year: 2007
  7. An Endogenous Ah Receptor Ligand: Gene and Physiological Responses
    Thomas Gasiewicz; Fiscal Year: 2007
  8. EGCG Inhibits AhR and Carcinogenesis by Modulating Hsp90
    Thomas Gasiewicz; Fiscal Year: 2007
  9. MOLECULAR TOXICITY OF TCDD
    Thomas Gasiewicz; Fiscal Year: 2006
  10. MOLECULAR TOXICITY OF TCDD
    Thomas Gasiewicz; Fiscal Year: 2000

Collaborators

  • Thomas H Thatcher
  • Ellen C Henry
  • PATRICIA JANET SIME
  • S Welle
  • Kameshwar P Singh
  • Fanny L Casado
  • Jeffrey C Bemis
  • Gary D Minsavage
  • Lisa A Opanashuk
  • Russell W Garrett
  • Mary A Williamson
  • Christine M Palermo
  • Amber Wyman
  • Michael D Laiosa
  • Zhengyu Yin
  • Carolyn J Baglole
  • Loretta L Collins
  • Elizabeth P Ryan
  • Daniel A Nazarenko
  • Carissa R Filbrandt
  • Junguo Zhou
  • Jun Guo Zhou
  • Frank A Middleton
  • Jeffrey H Mills
  • Zhi Wei Lai
  • Allen E Silverstone
  • Sanjay B Maggirwar
  • Bryan D Thompson
  • Daniel P Dever
  • Richard P Phipps
  • Andrew I Brooks
  • Tzong Jen Sheu
  • Raymond B Baggs
  • Jonathan D Holz
  • Napoleon F Alejandro
  • Mary Mulcahey
  • J Edward Puzas
  • Claire A Westlake
  • Berislav Zlokovic
  • Lisa Opanashuk
  • Zhenhua Wu
  • Sang Ki Park
  • Daria P Vorojeikina
  • Stephen D Dertinger
  • Gregory E Wilding
  • Amy L Lavin

Detail Information

Publications24

  1. pmc The aryl hydrocarbon receptor has a normal function in the regulation of hematopoietic and other stem/progenitor cell populations
    Kameshwar P Singh
    Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA
    Biochem Pharmacol 77:577-87. 2009
    ..It is also reasonable to hypothesize that this protein has an important function in the regulation of other tissue stem cell populations. Suggestive evidence is consistent with a role in skin and neural stem cells...
  2. pmc TCDD and a putative endogenous AhR ligand, ITE, elicit the same immediate changes in gene expression in mouse lung fibroblasts
    Ellen C Henry
    Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA
    Toxicol Sci 114:90-100. 2010
    ..Furthermore, if the difference in toxicity between TCDD and ITE is mediated by differences in gene expression, then it is likely that secondary changes enabled by the persistent TCDD, but not by the shorter lived ITE, are responsible...
  3. pmc The aryl hydrocarbon receptor has an important role in the regulation of hematopoiesis: implications for benzene-induced hematopoietic toxicity
    Thomas A Gasiewicz
    Department of Environmental Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
    Chem Biol Interact 184:246-51. 2010
    ..Defining the molecular mechanisms by which these events occur may lead to the identification of previously undefined roles of this transcription factor in human diseases, particularly those caused or affected by xenobiotics...
  4. ncbi request reprint The aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin alters the circadian rhythms, quiescence, and expression of clock genes in murine hematopoietic stem and progenitor cells
    Russell W Garrett
    Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester Medical Center, 601 Elmwood Avenue, Box EHSC, Rochester, NY 14642, USA
    Mol Pharmacol 69:2076-83. 2006
    ..Together, these data demonstrate that activation of the AhR by TCDD disrupts the circadian rhythms associated with murine hematopoietic precursors...
  5. ncbi request reprint 2,3,7,8-tetrachlorodibenzo-p-dioxin does not directly alter the phenotype of maturing B cells in a murine coculture system
    Amber Wyman
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    Toxicol Appl Pharmacol 180:164-77. 2002
    ..These results suggest that the maturing B220+ B cell is not the direct target for TCDD-induced bone marrow B-cell alterations...
  6. pmc Treatment of mice with the Ah receptor agonist and human carcinogen dioxin results in altered numbers and function of hematopoietic stem cells
    Kameshwar P Singh
    Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA
    Carcinogenesis 30:11-9. 2009
    ..Overall, these data are consistent with the hypothesis that TCDD, through AhR activation, alters the ability of HSCs to respond appropriately to signals within the marrow microenvironment...
  7. pmc The aryl hydrocarbon receptor attenuates tobacco smoke-induced cyclooxygenase-2 and prostaglandin production in lung fibroblasts through regulation of the NF-kappaB family member RelB
    Carolyn J Baglole
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Biol Chem 283:28944-57. 2008
    ..The association between RelB and AhR may represent a new therapeutic and more selective target with which to combat inflammation-associated diseases...
  8. ncbi request reprint TCDD-induced alterations in gene expression profiles of the developing mouse paw do not influence morphological differentiation of this potential target tissue
    Jeffrey C Bemis
    Department of Environmental Medicine, Rochester, New York 14642, USA
    Toxicol Sci 95:240-8. 2007
    ..However, the linkage of these changes to detectable biological outcomes in the paw remains unclear...
  9. ncbi request reprint Epigallocatechin gallate inhibits aryl hydrocarbon receptor gene transcription through an indirect mechanism involving binding to a 90 kDa heat shock protein
    Christine M Palermo
    Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA
    Biochemistry 44:5041-52. 2005
    ..This is the first time EGCG has been demonstrated to directly bind hsp90 and the first indication that GT may exert its chemopreventive effects through an interaction with the common chaperone hsp90...
  10. ncbi request reprint Aryl hydrocarbon receptor expression and activity in cerebellar granule neuroblasts: implications for development and dioxin neurotoxicity
    Mary A Williamson
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    Toxicol Sci 83:340-8. 2005
    ..These data suggest that (1) granule neuroblasts are direct targets for developmental AhR-mediated TCDD neurotoxicity and (2) TCDD exposure may disrupt granule cell neurogenesis...
  11. ncbi request reprint Presence and functional activity of the aryl hydrocarbon receptor in isolated murine cerebral vascular endothelial cells and astrocytes
    Carissa R Filbrandt
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Box EHSC, 575 Elmwood Avenue, Rochester, NY 14642, USA
    Neurotoxicology 25:605-16. 2004
    ..Together these data indicate endothelial cells and astrocytes are responsive to TCDD through the AhR-mediated pathway and therefore could be targets of toxicity...
  12. pmc The aryl hydrocarbon receptor: regulation of hematopoiesis and involvement in the progression of blood diseases
    Fanny L Casado
    Department of Environmental Medicine, University of Rochester School of Medicine, 601 Elmwood Avenue, Box EHSC, Rochester, NY 14642, USA
    Blood Cells Mol Dis 44:199-206. 2010
    ..Studies highlighting AhR regulation of HSCs/HPCs provide a rational framework to understand their biology, a role of the AhR in hematopoietic diseases, and a means to develop interventions for these diseases...
  13. ncbi request reprint Expression and activity of aryl hydrocarbon receptors in development and cancer
    Thomas A Gasiewicz
    Department of Environmental Medicine, University of Rochester Medical Center, Rochester, NY, USA
    Crit Rev Eukaryot Gene Expr 18:279-321. 2008
    ..Here we describe the current understanding of how the AhR may function to regulate both normal and cancerous tissue growth and development...
  14. pmc (-)-Epigallocatechin-3-gallate is a novel Hsp90 inhibitor
    Zhengyu Yin
    Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA
    Biochemistry 48:336-45. 2009
    ..EGCG also modified the association of hsp90 with several cochaperones. Overall, these data indicate that EGCG is a novel hsp90 inhibitor. Further studies are needed to determine if this has a role in the antitumor actions of EGCG...
  15. pmc Identification of stage-specific gene modulation during early thymocyte development by whole-genome profiling analysis after aryl hydrocarbon receptor activation
    Michael D Laiosa
    Department of Environmental Medicine, University of Rochester, Rochester, New York, USA
    Mol Pharmacol 77:773-83. 2010
    ..These seven genes are novel targets for modulation by the TCDD-activated AHR and may be involved in the observed cell-cycle arrest and suppression of early thymocyte development...
  16. doi request reprint 2,3,7,8-Tetracholorodibenzo-p-dioxin exposure disrupts granule neuron precursor maturation in the developing mouse cerebellum
    Loretta L Collins
    Department of Environmental Medicine, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA
    Toxicol Sci 103:125-36. 2008
    ..Together, our data suggest that TCDD disrupts a normal physiological role of AhR, resulting in compromised GNP maturation and neuroblast survival, which impacts final cell number in the cerebellum...
  17. ncbi request reprint Environmental toxicants may modulate osteoblast differentiation by a mechanism involving the aryl hydrocarbon receptor
    Elizabeth P Ryan
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
    J Bone Miner Res 22:1571-80. 2007
    ..The AHR may not only mediate the effects of toxicants, but with an as yet unidentified ligand, be involved in the differentiation pathways of osteoblasts...
  18. pmc Aryl hydrocarbon receptor-deficient mice develop heightened inflammatory responses to cigarette smoke and endotoxin associated with rapid loss of the nuclear factor-kappaB component RelB
    Thomas H Thatcher
    Department of Medicine, University of Rochester, Rochester, New York 14642, USA
    Am J Pathol 170:855-64. 2007
    ....
  19. ncbi request reprint Coplanar polychlorinated biphenyls activate the aryl hydrocarbon receptor in developing tissues of two TCDD-responsive lacZ mouse lines
    Jeffrey C Bemis
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, New York 14642, USA
    Toxicol Sci 87:529-36. 2005
    ....
  20. ncbi request reprint The aryl hydrocarbon receptor (AhR) tyrosine 9, a residue that is essential for AhR DNA binding activity, is not a phosphoresidue but augments AhR phosphorylation
    Gary D Minsavage
    Department of Environmental Medicine, School of Medicine, University of Rochester, 575 Elmwood Avenue, Rochester, NY 14642, USA
    J Biol Chem 279:20582-93. 2004
    ..Overall, AhR tyrosine 9, which is not a phosphorylated residue itself but is required for DNA binding, appears to play a crucial role in AhR activity by permitting proper phosphorylation of the AhR...
  21. ncbi request reprint 3'-methoxy-4'-nitroflavone, a reported aryl hydrocarbon receptor antagonist, enhances Cyp1a1 transcription by a dioxin responsive element-dependent mechanism
    Junguo Zhou
    Department of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA
    Arch Biochem Biophys 416:68-80. 2003
    ..However, depending on its concentration as well as the promoter context of a particular gene, the ability of 3'M4'NF to act as an AhR antagonist or agonist may appear different for various genes...
  22. ncbi request reprint Species-specific transcriptional activity of synthetic flavonoids in guinea pig and mouse cells as a result of differential activation of the aryl hydrocarbon receptor to interact with dioxin-responsive elements
    Jun Guo Zhou
    Molecular Toxicology and Environmental Medicine Program, School of Medicine and Dentistry, University of Rochester, Rochester, New York 14642, USA
    Mol Pharmacol 63:915-24. 2003
    ....
  23. pmc Aryl hydrocarbon receptor activation in hematopoietic stem/progenitor cells alters cell function and pathway-specific gene modulation reflecting changes in cellular trafficking and migration
    Fanny L Casado
    Department of Environmental Medicine, University of Rochester, Rochester, NY, USA
    Mol Pharmacol 80:673-82. 2011
    ..These data support a molecular mechanism for an AhR ligand to disrupt the homeostatic cell signaling of HSCs that may promote altered HSC function...
  24. ncbi request reprint Mutational analysis of the mouse aryl hydrocarbon receptor tyrosine residues necessary for recognition of dioxin response elements
    Gary D Minsavage
    Department of Environmental Medicine, School of Medicine, University of Rochester, Rochester, NY 14642, USA
    Arch Biochem Biophys 412:95-105. 2003
    ..Overall, these data strongly suggest that the putative posttranslational modification at, or mediated by, tyrosine 9, and not any other individual mouse AhR tyrosine residue, is necessary for AhR DRE binding and transcriptional activity...

Research Grants56

  1. Ah Receptor Dysregulation Alters Hematopoietic Stem Cells
    Thomas A Gasiewicz; Fiscal Year: 2011
    ..Furthermore, these events are intimately tied with the process of aging and a variety of diseases, including cancer, whose incidence increases with age. ..
  2. EFFECT OF TCDD ON T LYMPHOCYTE DIFFERENTIATION
    Thomas Gasiewicz; Fiscal Year: 2002
    ..Finally, recent data has suggested a role of the AhR in the normal development of the immune system. Immune progenitor cells in animals lacking the AhR will be further characterized to determine this. ..
  3. DEVELOPMENTAL ACTIVITY OF AH RECEPTOR IN VIVO
    Thomas Gasiewicz; Fiscal Year: 2001
    ..Additional studies will determine the modulated expression of the transgene following exposure of developing animals to TCDD. ..
  4. Developmental Activity of the Ah Receptor
    Thomas Gasiewicz; Fiscal Year: 2005
    ..These data will provide for the first time information on the cell and gene targets associated with in vivo responses to TCDD. ..
  5. Ah Receptor Dysregulation Alters Hematopoietic Stem Cells
    Thomas A Gasiewicz; Fiscal Year: 2010
    ..Furthermore, these events are intimately tied with the process of aging and a variety of diseases, including cancer, whose incidence increases with age. ..
  6. Effects of TCDD on T Lymphocyte Differentiation
    Thomas Gasiewicz; Fiscal Year: 2007
    ..Further studies examining phenotypic alterations and patterns of stem cell commitment in AhR null allele cells will further define a putative role of the AhR. ..
  7. An Endogenous Ah Receptor Ligand: Gene and Physiological Responses
    Thomas Gasiewicz; Fiscal Year: 2007
    ..Understanding the role of ITE and the AhR in modulating inflammatory processes may lead to possible therapeutic interventions. ..
  8. EGCG Inhibits AhR and Carcinogenesis by Modulating Hsp90
    Thomas Gasiewicz; Fiscal Year: 2007
    ..Additional studies will determine if EGCG alters the levels and/or activity of several hsp90 client proteins that may play a role in the malignant transformation or growth of tumor cells. ..
  9. MOLECULAR TOXICITY OF TCDD
    Thomas Gasiewicz; Fiscal Year: 2006
    ..Overall, data from these investigations will indicate the precise amino acid residues that are phosphorylated and their functional significance. ..
  10. MOLECULAR TOXICITY OF TCDD
    Thomas Gasiewicz; Fiscal Year: 2000
    ..Finally, additional studies will define nuclear factors that influence AhR-Arnt transcriptional activity and determine how altered phosphorylation of these affect this activity. ..
  11. EFFECT OF TCDD ON THYMIC LYMPHOCYTE DIFFERENTIATION
    Thomas Gasiewicz; Fiscal Year: 1992
    ..The expression of genes which determine T-cell functionally will also be examined. The studies will focus on the T-cell Receptor (TcR) and the functionally linked molecule CD3...
  12. MOLECULAR TOXICITY OF TCDD
    Thomas Gasiewicz; Fiscal Year: 1993
    ..Finally, the possibility that the ART protein may represent only one of a family of proteins having the ability to interact with the AhR in a TCDD-dependent manner to form a gene regulatory complex will be examined...
  13. MOLECULAR TOXICITY OF TCDD
    Thomas Gasiewicz; Fiscal Year: 1991
    ..These studies may suggest what controls this receptor in vivo, as well as the possible physiological role of this molecule...