- BS, Montana State University, 1967
- MS, Montana State University, 1969
- PhD, University of Louisville, 1973
Selected Recent Publications (2010-2011):
Hanson, Miranda L., Kathleen M. Brundage, Rosana Schafer, Janet Tou and John B. Barnett. 2010. Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in altered thymocyte development, Toxicol Applied Pharmacol 242(2):136-145.
Robinson, Lisa J, Harry C Blair, John B Barnett, Mone Zaidi, Christopher L.-H. Huang. 2010 Regulation of Bone Turnover by Calcium-regulated Calcium Channels. Ann. NY Acad Sc 1192(1):351-357.
Zhou, Yandong, Tricia L. Lewis, Lisa J. Robinson, Kathy M. Brundage, Rosana Schafer, Karen H. Martin, Harry C. Blair, Jonanthan Soboloff and John B. Barnett. 2011. The Role of Calcium Release Activation Calcium Channels in Osteoclast Differentiation. J. Cellular Physiology 226(4):1082-1089.
Boyce, Brandon M., Brock A. Lindsey, Nina B Clovis, E. Suzanne Smith, Gerald R. Hobbs, David F. Hubbard, Sanford E. Emery, John B. Barnett, and Bingyun Li. 2011. Additive effects of exogenous IL-12 supplementation and antibiotic treatment in infection prophylaxis. J. Orthopaedic Research, in press.
Jing, Yi, Ling-Zhi Liu, Yue Jiang, Yingxue Zhu, Nancy Lan Guo, John Barnett, Yon Rojanasakul, Faton Agani, and Bing-Hua Jiang. 2011 Cadmium Increases HIF-1 and VEGF Expression through ROS, ERK and AKT Signaling Pathways and Induces Malignant Transformation of Human Bronchial Epithelial Cells Toxicological Sciences, in press (available on line)
View more at PubMed
The work in our laboratory focuses on the consequences to the immune system of exposure to xenobiotic compounds as well as the mechanisms of the carcinogenic effects of these compounds. It is our goal to utilize their known immunomodulary effects to assist in understanding the basic biology of the immune cells.
Immunopathology of Atrazine
Atrazine is the most heavily used single herbicide in the USA with annual application rates estimated by the US Environmental Protection Agency (EPA) approaching 82 million pounds. We have investigated the effects of prenatal exposure to atrazine on the developing immune system by testing its effect on a central (thymus) and a peripheral (spleen) immune compartment, determining the developmental immunotoxic effects of atrazine on the ability of the offspring to mount a robust immune response, and determining the developmental immunotoxic effects of atrazine on the ability of the offspring to resist infection by virulent bacteria. The result of these experiments indicated that prenatal exposure does affect the immune system of the offspring. Further studies on the effects of atrazine on immune function have now shifted to an in vitro exposure model so that we can assess the mechanism of any direct effects of atrazine on NK and T cell cytolytic function.
Immunopathology of Propanil
Propanil is a post-emergent herbicide that is used extensively on rice world-wide. Studies using spleen cells or macrophages from mice treated with propanil in vivo demonstrate that it has an anti-inflammatory activity with decreases in ex vivo interferon-γ (IFNγ, granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-2 and IL-6 production by spleen cells and IL-6 and tumor necrosis factor (TNF)-α production by macrophages. IL-2 is an essential autocrine and paracrine growth factor of the immune system produced by activated T lymphocytes. Our data indicate that propanil inhibits at least two signaling pathways that control IL-2 production: the ras (MAP kinase) pathway leading to c-jun activation; and the phospholipase C (PLC)-calcium-dependent pathway leading to the activation of nuclear factor activating factor (NF-AT), nuclear factor of κB (NF-κB) and other transcription factors. Another pathway leading to T cell activation has recently been identified. The overall question that arises from these studies is whether the data are indicative of a single common target central to all the pathways or indicative of multiple targets for propanil. Current experiments are focused on determining the step(s) in the c-jun activation pathway that propanil affects in human T lymphocytes, determining the effect of propanil on early receptor-mediated signaling events that lead to NF-AT activation, and determining the step(s) in the NF-κB signaling pathway affected by propanil. Our more recent research goal is to develop 3, 4-dichloroproprionanilide (DCPA, aka propanil) as a specific Ca2+ channel inhibitor to more completely understand the role of Ca2+ in the activation of T cells.
Immunopathology and Carcinogenesis of Cadmium
Sonic Hedgehog (SHH), an important signaling molecule that helps orchestrate embryonic development, has recently been shown to also function in the renewal of immune cells during adult life as well as during fetal development. Cadmium (Cd) is a heavy metal that is both an environmental contaminant as well as a significant component of cigarette smoke. Cd is also a known mammalian teratogen that causes forelimb ectrodactyly in rodents. Although extensively studied as a teratogen, only very recent evidence provides a mechanism for this teratological effect, that is, that SHH signaling is altered in the offspring of Cd treated dams.
We are currently collecting preliminary data to connect the potential of Cd to alter the development of thymocytes during fetal development. The importance of this work is both to develop a valuable probe to understand the role of SHH in fetal thymic development as well as determine the potential risk for the offspring exposed to Cd in utero. One specific aim was proposed: Establish that prenatal Cd disruption of SHH signaling alters T cell development in the mouse fetus. This specific aim is to test the hypothesis that prenatal Cd exposure will lower SHH levels resulting in a lower percentage of double positive thymocytes in the newborn.
Cadmium and other heavy metals are carcinogenic. We are part of a multi-investigator team that is studying the effects of these heavy metals on lung cells with the goal of understanding the mechanism of their carcinogenesis.
B.S., Microbiology, Montana State University, 1967
M.S., Microbiology, Montana State University, 1969
Ph.D., Microbiology/Immunology, University of Louisville, 1973
Post-Doc, Immunology, University of Tennessee, 1973 - 1975
Positions and Honors
Assistant, Associate, Professor, Department Microbiology/Immunology
University Arkansas for Medical Sciences, Little Rock, AR - 1975 - 1991
Associate Dean for Research, College of Medicine
University Arkansas for Medical Sciences, Little Rock AR - 1989-1991
Director, West Virginia University Systems Biology Initiative
WVU, Morgantown WV - 2003-2006
Director, WVU Center for Immunopathology and Microbial Pathogenesis
WVU, Morgantown WV - 2005-2008
Professor and Chair, Microbiology, Immunology & Cell Biology
West Virginia U., Morgantown WV - 1992-present
NIH Review Groups
Member, Environment Health Sciences Review Committee (Study Section), NIEHS, 1986-1990
NIH ad hoc Reviewer, 1990-present (approx 2 study sections per year)
Member & Chair (three times), Special Study Section for the evaluation of NIEHS Super Fund Applications
Member, Inflammation and Innate Immunity CSR Study Section, 2011-2014
Selected Peer-Reviewed Publications (Selected From >95 Articles)
- Theus SA, Lau KA, Tabor DR, Soderberg LS, Barnett JB. In vivo prenatal chlordane exposure induces development of endogenous inflammatory macrophages. J Leukoc Biol. 1992 Apr;51(4):366-72. PMID: 1564400
- Theus SA, Tabor DR, Soderberg LS, Barnett JB. Macrophage tumoricidal mechanisms are selectively altered by prenatal chlordane exposure. Agents Actions. 1992 Sep;37(1-2):140-6. PMID: 1456175
- Blyler G, Landreth KS, Barnett JB. Gender-specific effects of prenatal chlordane exposure on myeloid cell development. Fundam Appl Toxicol. 1994 Aug;23(2):188-93. PMID: 7982527
- Zhao W, Schafer R, Barnett JB. Propanil affects transcriptional and posttranscriptional regulation of IL-2 expression in activated EL-4 cells. Toxicol Appl Pharmacol. 1999 Jan 15;154(2):153-9. PMID: 9925799
- Frost LL, Neeley YX, Schafer R, Gibson LF, Barnett JB. Propanil inhibits tumor necrosis factor-alpha production by reducing nuclear levels of the transcription factor Nuclear Factor-kappaB in the macrophage cell line IC-21. Toxicol Appl Pharmacol. 2001 May 1;172(3):186-93. PMID: 11312646
- de la Rosa P, Barnett JB, Schafer R. Characterization of thymic atrophy and the mechanism of thymocyte depletion after in vivo exposure to a mixture of herbicides. J Toxicol Environ Health A. 2005 Jan 22;68(2):81-98. PMID: 15762548
- Salazar KD, de la Rosa P, Barnett JB, Schafer R. The polysaccharide antibody response after Streptococcus pneumoniae vaccination is differentially enhanced or suppressed by 3,4-dichloropropionanilide and 2,4-dichlorophenoxyacetic acid. Toxicol Sci. 2005 Sep;87(1):123-33. Epub 2005 Jun 23. PMID: 15976183
- Rowe AM, Brundage KM, Schafer R, Barnett JB. Immunomodulatory effects of maternal atrazine exposure on male Balb/c mice. Toxicol Appl Pharmacol. 2006 Jul 1;214(1):69-77. Epub 2006 Jan 27. PMID: 16443249
- Salazar KD, Miller MR, Barnett JB, Schafer R. Evidence for a novel endocrine disruptor: the pesticide propanil requires the ovaries and steroid synthesis to enhance humoral immunity. Toxicol Sci. 2006 Sep;93(1):62-74. Epub 2006 Jun 20. PMID: 16788000
- Ustyugova IV, Frost LL, Van Dyke K, Brundage KM, Schafer R, Barnett JB. 3,4-dichloropropionaniline suppresses normal macrophage function. Toxicol Sci. 2007 Jun;97(2):364-74. Epub 2007 Mar 12. PMID: 17355946
- Rowe AM, Brundage KM, Barnett JB. In vitro atrazine-exposure inhibits human natural killer cell lytic granule release. Toxicol Appl Pharmacol. 2007 Jun 1;221(2):179-88. PMID: 17475299
- Rowe AM, Brundage KM, Barnett JB. Developmental immunotoxicity of atrazine in rodents. Basic Clin Pharmacol Toxicol. 2008 Feb;102(2):139-45. Review. PMID: 18226067
- Hanson ML, Brundage KM, Schafer R, Tou JC, Barnett JB. 2010 Prenatal cadmium exposure dysregulates sonic hedgehog and Wnt/beta-catenin signaling in the thymus resulting in altered thymocyte development. Toxicol Appl Pharmacol. 242(2):136-145 PMID: 19818801
- Zhou, Y, T. Lewis, L. Robinson, K. Brundage, R. Schafer, K. Martin, H. Blair, J. Soboloff, and J. Barnett. 2010. The Role of Calcium Release Activated Calcium Channels in Osteoclast Differentiation. J. Cell Physiol. [Epub ahead of print] PMID: 20839232
- Jing, Yi, Ling-Zhi Liu, Yue Jiang, Yingxue Zhu, Nancy Lan Guo, John Barnett, Yon Rojanasakul, Faton Agani, and Bing-Hua Jiang. 2011 Cadmium Increases HIF-1 and VEGF Expression through ROS, ERK and AKT Signaling Pathways and Induces Malignant Transformation of Human Bronchial Epithelial Cells Toxicological Sciences, in press (available on line)
R21 National Inst. of Health (NIEHS) ES014698 - 3/15/2009–4/31/2011
Precocious immune senescence induced by pre- & postnatal atrazine exposure
Role: Principal Investigator – overall supervision of the project, design of expts, publication of data, etc.
Goal: To understand the effects of prenatal atrazine exposure on the central (thymus and bone marrow) and peripheral (lung) immune system at 6, 9 and 12 months of age.
R03 National Inst. of Health (NIEHS) ES015539 Barnett (PI) - 8/1/2007-07/31/09
National Inst. of Health (N.I.E.H.S.) Cadmium-induced changes in sonic Hedgehog signaling and T cell development during embryogenesis
Role: Principal Investigator – overall supervision of the project, design of expts, publication of data, etc.
Goal: To understand the effects of Cd on fetal T cell embryogenesis
Sara Crile Allen and James Frederick Allen Lung Cancer Program