B. Paige Lawrence
| Title | Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Environmental Medicine |
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| Address | University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 850
Rochester NY 14642
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| Title | Professor |
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| Institution | School of Medicine and Dentistry |
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| Department | Microbiology and Immunology |
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| 1986 |
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| Phi Beta Kappa, Skidmore College Chapter | | 1986 |
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| Periclean Honor Society | Honorary Society for academic excellence | | 1986 |
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| Charlotte W. Fahey Prize for academic achievement in the field of Chemistry | | 1995 |
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| National Research Service Award (NRSA) Postdoctoral Fellowship | NIEHS, NIH | | 2003 |
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| Advisor Excellence Award | Graduate & Professional Student Association | | 2004 |
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| Independent Scientist Award (K02) | NIH | | 2006 |
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| Outstanding Young Investigator Award | Immunotoxicology Specialty Section, Society of Toxicology | | 2007 |
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| Service Recognition Award for Excellence in Mentoring | Women in Toxicology Special Interest Group of the Society of Tox |
Environmental signaling, immune function, and cellular development
Environmental signals influence the behavior of cells throughout the body. In some cases this is part of normal physiology, but in other instances environmental signals cue cells to work aberrantly. When this occurs, pathology generally ensues, leading to poorer health. For many chemicals from our environment the mechanisms by which they perturb physiology are largely unknown, and determining these mechanisms forms the basis of most of our research. We have several interrelated projects currently underway.
The aryl hydrocarbon receptor (AhR)
The AhR is a ligand-activated transcription factor that mediates many environmental signals. Its normal function in the body is unknown, but numerous exogenous chemicals bind to AhR, affecting gene expression and cell function. A major focus of our research is to delineate the mechanisms by which the AhR regulates the development and function of the immune system. To accomplish this, we often use influenza viruses, as they are common human pathogens, and because humans exposed to pollutants that bind AhR often have more respiratory illness. We often use the pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) because it binds the AhR with very high affinity and causes sustained activation. This makes it a powerful research tool, as we can probe AhR-regulated pathways by exploiting the knowledge gained when they are perturbed. Also, TCDD represents a large group of highly toxic chemicals found throughout the world, and daily low-level exposure to them has been linked to impairment of the immune, reproductive, and endocrine systems. Current projects seek to understand AhR's normal role in, and how pollutants impact, the immune system and developing organs, and include the following projects:
• The role of AhR in immune response to respiratory viral infection
• The role of AhR in programming the developing immune system
• The role of the AhR in mammary gland differentiation and lactogenesis
There is now compelling evidence that developmental exposures to chemicals from our environment lead to disease later in life, and our interest in how environmental signals alter the developing immune system extends beyond AhR and dioxin. We have two additional funded projects in this area.
Neonatal oxygen supplementation and respiratory viral infection
In collaboration with Dr. Michael O'Reilly, we are studying the effects of neonatal oxygen supplementation on pulmonary immune function. Premature infants are often given high oxygen supplementation, which has substantially reduced premature infant mortality. However, even as adolescents, these infants exhibit reduced lung function and are more likely to be re-hospitalized due to respiratory viral infection. Using a mouse model, we are currently determining how neonatal high oxygen treatment disrupts the response to respiratory viral infection. Moreover, we are integrating our research findings with studies of immune responses in infected children who were born prematurely, which we hope will help us identify novel therapeutic opportunities for improving the health of children born prematurely.
Developmental immunotoxicity of bisphenol A (BPA)
BPA is used in the manufacture of polycarbonate plastics and epoxy resins, and is one of the highest volume chemicals produced worldwide. Existing but very limited data indicate that maternal exposure adversely impacts the developing immune system, and this is a cause for concern. Yet, our current inadequate understanding of BPA's developmental immunotoxicity fetters progress toward comprehensive assessment of the human health effects of BPA. To address this we have started a new project in which we will conduct the most detailed analysis to-date of the impact of the BPA on immune system development and function in the context of animal models of human diseases, such as asthma, influenza, and inflammatory bowel disease.
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Giannandrea M, Yee M, O'Reilly MA, Lawrence BP. Memory CD8+ T Cells Are Sufficient To Alleviate Impaired Host Resistance to Influenza A Virus Infection Caused by Neonatal Oxygen Supplementation. Clin Vaccine Immunol. 2012 Sep; 19(9):1432-41.
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O'Reilly MA, Yee M, Buczynski BW, Vitiello PF, Keng PC, Welle SL, Finkelstein JN, Dean DA, Lawrence BP. Neonatal oxygen increases sensitivity to influenza a virus infection in adult mice by suppressing epithelial expression of ear1. Am J Pathol. 2012 Aug; 181(2):441-51.
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Roy A, Bauer SM, Lawrence BP. Developmental exposure to bisphenol a modulates innate but not adaptive immune responses to influenza a virus infection. PLoS One. 2012; 7(6):e38448.
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Buczynski BW, Yee M, Paige Lawrence B, O'Reilly MA. Lung development and the host response to influenza A virus are altered by different doses of neonatal oxygen in mice. Am J Physiol Lung Cell Mol Physiol. 2012 May; 302(10):L1078-87.
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Lawrence BP, Sherr DH. You AhR what you eat? Nat Immunol. 2012; 13(2):117-9.
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Lew BJ, Manickam R, Lawrence BP. Activation of the aryl hydrocarbon receptor during pregnancy in the mouse alters mammary development through direct effects on stromal and epithelial tissues. Biol Reprod. 2011 Jun; 84(6):1094-102.
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Jusko TA, De Roos AJ, Schwartz SM, Lawrence BP, Palkovicova L, Nemessanyi T, Drobna B, Fabisikova A, Kocan A, Jahnova E, Kavanagh TJ, Trnovec T, Hertz-Picciotto I. Maternal and early postnatal polychlorinated biphenyl exposure in relation to total serum immunoglobulin concentrations in 6-month-old infants. J Immunotoxicol. 2011 Jan-Mar; 8(1):95-100.
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Winans B, Humble MC, Lawrence BP. Environmental toxicants and the developing immune system: a missing link in the global battle against infectious disease? Reprod Toxicol. 2011 Apr; 31(3):327-36.
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Wang T, Gavin HM, Arlt VM, Lawrence BP, Fenton SE, Medina D, Vorderstrasse BA. Aryl hydrocarbon receptor activation during pregnancy, and in adult nulliparous mice, delays the subsequent development of DMBA-induced mammary tumors. Int J Cancer. 2011 Apr 1; 128(7):1509-23.
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Jin GB, Moore AJ, Head JL, Neumiller JJ, Lawrence BP. Aryl hydrocarbon receptor activation reduces dendritic cell function during influenza virus infection. Toxicol Sci. 2010 Aug; 116(2):514-22.
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Jusko TA, De Roos AJ, Schwartz SM, Lawrence BP, Palkovicova L, Nemessanyi T, Drobna B, Fabisikova A, Kocan A, Sonneborn D, Jahnova E, Kavanagh TJ, Trnovec T, Hertz-Picciotto I. A cohort study of developmental polychlorinated biphenyl (PCB) exposure in relation to post-vaccination antibody response at 6-months of age. Environ Res. 2010 May; 110(4):388-95.
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Lew BJ, Collins LL, O'Reilly MA, Lawrence BP. Activation of the aryl hydrocarbon receptor during different critical windows in pregnancy alters mammary epithelial cell proliferation and differentiation. Toxicol Sci. 2009 Sep; 111(1):151-62.
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Collins LL, Lew BJ, Lawrence BP. TCDD exposure disrupts mammary epithelial cell differentiation and function. Reprod Toxicol. 2009 Jul; 28(1):11-7.
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Head JL, Lawrence BP. The aryl hydrocarbon receptor is a modulator of anti-viral immunity. Biochem Pharmacol. 2009 Feb 15; 77(4):642-53.
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O'Reilly MA, Marr SH, Yee M, McGrath-Morrow SA, Lawrence BP. Neonatal hyperoxia enhances the inflammatory response in adult mice infected with influenza A virus. Am J Respir Crit Care Med. 2008 May 15; 177(10):1103-10.
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Lawrence BP, Denison MS, Novak H, Vorderstrasse BA, Harrer N, Neruda W, Reichel C, Woisetschläger M. Activation of the aryl hydrocarbon receptor is essential for mediating the anti-inflammatory effects of a novel low-molecular-weight compound. Blood. 2008 Aug 15; 112(4):1158-65.
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Hogaboam JP, Moore AJ, Lawrence BP. The aryl hydrocarbon receptor affects distinct tissue compartments during ontogeny of the immune system. Toxicol Sci. 2008 Mar; 102(1):160-70.
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Teske S, Bohn AA, Hogaboam JP, Lawrence BP. Aryl hydrocarbon receptor targets pathways extrinsic to bone marrow cells to enhance neutrophil recruitment during influenza virus infection. Toxicol Sci. 2008 Mar; 102(1):89-99.
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Neff-LaFord H, Teske S, Bushnell TP, Lawrence BP. Aryl hydrocarbon receptor activation during influenza virus infection unveils a novel pathway of IFN-gamma production by phagocytic cells. J Immunol. 2007 Jul 1; 179(1):247-55.
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Lawrence BP. Environmental toxins as modulators of antiviral immune responses. Viral Immunol. 2007; 20(2):231-42.
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Lawrence BP, Roberts AD, Neumiller JJ, Cundiff JA, Woodland DL. Aryl hydrocarbon receptor activation impairs the priming but not the recall of influenza virus-specific CD8+ T cells in the lung. J Immunol. 2006 Nov 1; 177(9):5819-28.
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Vorderstrasse BA, Lawrence BP. Protection against lethal challenge with Streptococcus pneumoniae is conferred by aryl hydrocarbon receptor activation but is not associated with an enhanced inflammatory response. Infect Immun. 2006 Oct; 74(10):5679-86.
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Vorderstrasse BA, Cundiff JA, Lawrence BP. A dose-response study of the effects of prenatal and lactational exposure to TCDD on the immune response to influenza a virus. J Toxicol Environ Health A. 2006 Mar; 69(6):445-63.
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Bohn AA, Harrod KS, Teske S, Lawrence BP. Increased mortality associated with TCDD exposure in mice infected with influenza A virus is not due to severity of lung injury or alterations in Clara cell protein content. Chem Biol Interact. 2005 Aug 15; 155(3):181-90.
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Schmittgen TD, Gissel KA, Zakrajsek BA, Lawrence BP, Liu Q, Jupe ER, Lerner MR, Do SV, Brackett DJ. Diverse gene expression pattern during 5-fluorouridine-induced apoptosis. Int J Oncol. 2005 Aug; 27(2):297-306.
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Teske S, Bohn AA, Regal JF, Neumiller JJ, Lawrence BP. Activation of the aryl hydrocarbon receptor increases pulmonary neutrophilia and diminishes host resistance to influenza A virus. Am J Physiol Lung Cell Mol Physiol. 2005 Jul; 289(1):L111-24.
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Vorderstrasse BA, Cundiff JA, Lawrence BP. Developmental exposure to the potent aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin Impairs the cell-mediated immune response to infection with influenza a virus, but enhances elements of innate immunity. J Immunotoxicol. 2004 Apr; 1(2):103-12.
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Lawrence BP, Vorderstrasse BA. Activation of the aryl hydrocarbon receptor diminishes the memory response to homotypic influenza virus infection but does not impair host resistance. Toxicol Sci. 2004 Jun; 79(2):304-14.
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Vorderstrasse BA, Fenton SE, Bohn AA, Cundiff JA, Lawrence BP. A novel effect of dioxin: exposure during pregnancy severely impairs mammary gland differentiation. Toxicol Sci. 2004 Apr; 78(2):248-57.
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Mitchell KA, Lawrence BP. T cell receptor transgenic mice provide novel insights into understanding cellular targets of TCDD: suppression of antibody production, but not the response of CD8(+) T cells, during infection with influenza virus. Toxicol Appl Pharmacol. 2003 Nov 1; 192(3):275-86.
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Neff-LaFord HD, Vorderstrasse BA, Lawrence BP. Fewer CTL, not enhanced NK cells, are sufficient for viral clearance from the lungs of immunocompromised mice. Cell Immunol. 2003 Nov; 226(1):54-64.
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Vorderstrasse BA, Bohn AA, Lawrence BP. Examining the relationship between impaired host resistance and altered immune function in mice treated with TCDD. Toxicology. 2003 Jun 3; 188(1):15-28.
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Mitchell KA, Lawrence BP. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) renders influenza virus-specific CD8+ T cells hyporesponsive to antigen. Toxicol Sci. 2003 Jul; 74(1):74-84.
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Lawrence BP, Warren TK, Luong H. Fewer T lymphocytes and decreased pulmonary influenza virus burden in mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). J Toxicol Environ Health A. 2000 Sep 15; 61(1):39-53.
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Warren TK, Mitchell KA, Lawrence BP. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses the humoral and cell-mediated immune responses to influenza A virus without affecting cytolytic activity in the lung. Toxicol Sci. 2000 Jul; 56(1):114-23.
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Lawrence BP, Will Y, Reed DJ, Kerkvliet NI. Gamma-glutamyltranspeptidase knockout mice as a model for understanding the consequences of diminished glutathione on T cell-dependent immune responses. Eur J Immunol. 2000 Jul; 30(7):1902-10.
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Mann KK, Matulka RA, Hahn ME, Trombino AF, Lawrence BP, Kerkvliet NI, Sherr DH. The role of polycyclic aromatic hydrocarbon metabolism in dimethylbenz[a]anthracene-induced pre-B lymphocyte apoptosis. Toxicol Appl Pharmacol. 1999 Nov 15; 161(1):10-22.
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Lawrence BP, Meyer M, Reed DJ, Kerkvliet NI. Role of glutathione and reactive oxygen intermediates in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced immune suppression in C57Bl/6 mice. Toxicol Sci. 1999 Nov; 52(1):50-60.
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Lee CA, Lawrence BP, Kerkvliet NI, Rifkind AB. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induction of cytochrome P450-dependent arachidonic acid metabolism in mouse liver microsomes: evidence for species-specific differences in responses. Toxicol Appl Pharmacol. 1998 Nov; 153(1):1-11.
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Lawrence BP, Kerkvliet NI. Role of altered arachidonic acid metabolism in 2,3,7, 8-tetrachlorodibenzo-p-dioxin-induced immune suppression in C57Bl/6 mice. Toxicol Sci. 1998 Mar; 42(1):13-22.
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Lawrence BP, Leid M, Kerkvliet NI. Distribution and behavior of the Ah receptor in murine T lymphocytes. Toxicol Appl Pharmacol. 1996 Jun; 138(2):275-84.
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Lawrence BP, Brown WJ. Inhibition of protein synthesis separates autophagic sequestration from the delivery of lysosomal enzymes. J Cell Sci. 1993 Jun; 105 ( Pt 2):473-80.
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Lawrence BP, Brown WJ. Autophagic vacuoles rapidly fuse with pre-existing lysosomes in cultured hepatocytes. J Cell Sci. 1992 Jul; 102 ( Pt 3):515-26.
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