Research Associate Professor
After completing a B.A. in Human Ecology at the College of the Atlantic in 1997, Celine received her Ph.D. in Pharmaceutical Sciences under Dr. Diana Lurie from the University of Montana in 2002. Following a postdoctoral fellowship in the laboratory of Dr. Andrij Holian in the Center for Environmental Health Sciences at the University of Montana. Currently, Celine is a Research Associate Professor in the Department of Biomedical and Pharmaceutical Sciences (2011) and faculty member of the Center for Biomolecular Structure and Dynamics and the Center for Environmental Health Sciences.
2011, 2013, 2014 Toxicology I
2011, 2012 Toxicology II
2003 Toxicology III
2003 Cardiovascular Pharmacology and Toxicology
2004, 2006, 2008 Neuro-Pharmacology & Neuro-Toxicology
2005, 2007, 2009, 2011, Fundamentals of Immunotoxicology
2009 Recent Advances in Clinical Medicine (ACPE CE Program)
1999-2003 The Exceptional Brain (Minority/disadvantaged OutreachProgram)
My research focuses on understanding how the environment influences overall health, with a particular emphasis on the immune system. In my laboratory, ‘environment’ broadly encompasses toxicants, pathogens, natural products, and therapeutic agents. My research seeks to define, at the cellular and molecular levels, precisely how environmental exposures modify the function of the innate immune system using a variety of triggers, such as inhaled particulates, models of asthma, as well as natural and synthetic ligands of the AhR. To conduct this research, we integrate many approaches, including mouse genetics, pharmacological and biochemical modifiers of cellular processes, gene-specific analyses, numerous immunological tools, microscopy, and state-of-the art multi-color flow cytometry. I strongly believe that a thorough understanding of the cellular and molecular mechanisms that regulate immune response to the environment will lead to the development of improved diagnostic tests, prognostic biomarkers, and therapeutics that can be used to halt or slow disease progression. With this in mind, current and future research projects in my laboratory include the following:
(1) Aryl hydrocarbon receptor (AhR) mediated regulation of IL-22 production by innate lymphocytes.
Innate lymphoid cells (ILCs) are a heterogeneous population of cells that function in lymphoid organogenesis, tissue remodeling, antimicrobial and antifungal immunity, and inflammation. Agents that affect the functionality of ILCs are capable of transforming mucosal immunity resulting in either altered susceptibility to disease or therapeutic benefit. Because AhR activation by both endogenous and exogenous AhR ligands is required for IL-22 expression by RORgt+ ILCs in vitro and in vivo, and IL-22 has emerged as a prospective mechanism to attenuate pulmonary inflammation, select AhR ligands may represent a means to therapeutically manipulate the function of ILCs and limit pulmonary inflammation. The purpose of this study is to establish that AhR ligands may be useful tools in the treatment of inflammatory lung diseases. We will utilize a select panel of natural and synthetic ligands to: 1) define how AhR activation affects phenotype and function of ILC3s, and 2) determine ligand-binding interactions that correlate with specific physiological outcomes within RORgt+ ILC3s. This is particularly innovative because it crosses biomedical disciplines and approaches molecular mechanisms of immune function from a fresh perspective. To our knowledge, no studies have determined the molecular mechanisms underlying the ability of ligands acting via the AhR to differentially modify functionality in RORgt+ ILC3s. Moreover, this project is innovative in that the knowledge gained regarding the AhR-ILC-IL-22 signaling axis will provide new targets for the management of respiratory diseases, which would have a significant, positive effect on human health. These studies will also enhance our knowledge of how environmental contaminants adversely affect human health by altering immune function.
(2) Understanding the role of the AhR in toxicant induced inflammatory skin disease.
The prevalence of skin inflammatory diseases such as atopic dermatitis (AD) and psoriasis is increasing worldwide affecting lives of millions of individuals. Exposure to environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs; major environmental pollutant in automobile exhaust, cigarette smoke, many foods and industrial waste) are reported to contribute to the prevalence and exacerbation of these skin inflammatory diseases. Although abnormal immune responses appear to drive disease, the mechanisms by which PAHs initiate skin inflammatory diseases remain unclear. Emerging evidence suggests that the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is an important player in skin integrity and skin immunity, and modulation of its activity can affect inflammatory lesions. AhR-induced genetic changes from pollutant exposure can affect signaling pathways and metabolites, which could serve as novel biomarkers of skin inflammatory
consequences from PAH exposures. The goals of this project are to understand the role of the AhR in inflammatory skin diseases, and evaluate the AhR as a target for more effective treatments against psoriasis. To our knowledge, no studies have determined the molecular mechanisms underlying the ability of pollutants acting via the AhR to differentially modify psoriasis. Moreover, this project is innovative in that the knowledge gained regarding the AhR signaling axis will provide new targets for the management of skin diseases, which would have a significant, positive effect on human health. These studies will also enhance our knowledge of how environmental contaminants adversely affect human health by altering immune function.
Non-allergic asthma is poorly defined and less well understood than allergic asthma, even though it represents a large proportion of total asthma cases (~40%) and affects millions of individuals worldwide. Inhaled pollutants such as ozone, cigarette smoke, and diesel exhaust particles (DEP) trigger non-allergic asthma. Although dysregulated immune responses are the root cause of disease, the mechanisms by which inhaled pollutants instigate non-allergic asthma remains unclear. Type 3 innate lymphoid cells (ILC3s) play an important, yet complex role in pulmonary immune responses through the secretion of cytokines that orchestrate destructive (IL-17) or protective (IL-22) events. The goals of this proposal are to: 1) define the mechanisms responsible for DEP-induced IL-17+ ILC3s, 2) investigate the mechanisms by which select AhR ligands promote IL-22+ ILC3s, and 3) explore the therapeutic potential of IL-22+ ILC3s to limit DEP-induced non-allergic asthma. This proposal is innovative because little information exists regarding the role of ILC3s in DEP-induced nonallergic asthma and how AhR signaling regulates the function of ILC3s. We expect that these studies will yield not only conceptual, but also technical innovations. Improving our knowledge of the signals and cues that stimulate and regulate ILC3s may lead to the development of new therapeutics for inflammatory lung diseases.
(4) Investigating the function of BMP signaling axis in thymic regeneration.
Although the thymus is highly sensitive to a range of physiological and pathological situations (e.g. infections, malnutrition, pregnancy, chemotherapy, and environmental pollutants), it exhibits a remarkable capacity to regenerate—which diminishes with age. Activation of the aryl hydrocarbon receptor (AhR) by acute exposure to the persistent environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin, TCDD) induces severe, yet transient thymic atrophy—with recovery to near baseline thymic weight and cellularity approximately 30 days afterwards. However, the mechanisms driving endogenous thymic regeneration remain poorly understood. We have identified the interleukin 22 (IL-22)—bone morphogenic protein (BMP) signaling network critical for recovery of thymic function following exposure to dioxin. The main goal of this proposal is to understand those IL-22—BMP signaling processes which underlying endogenous thymic regeneration so that they may be exploited into clinically relevant targets for thymic rejuvenation and restoration of healthy immunity. Furthermore, we anticipate that our studies will reveal novel pathways and cellular interactions that are broadly shared in other epithelial tissues during development, aging and rejuvenation.
Targeted deletion of the aryl hydrocarbon receptor in dendritic cells prevents thymic atrophy in response to dioxin. Beamer CA, Kreitinger JM, Cole SL, Shepherd DM. Arch Toxicol. 2018 Nov 29. doi: 10.1007/s00204-018-2366-x. [Epub ahead of print] PMID: 30499018
Isolation and Identification of Innate Lymphoid Cells (ILCs) for Immunotoxicity Testing. Tait Wojno ED, Beamer CA. Methods Mol Biol. 2018;1803:353-370. doi: 10.1007/978-1-4939-8549-4_21. PMID: 29882149
Environmental Immunology: Lessons Learned from Exposure to a Select Panel of Immunotoxicants. Kreitinger JM, Beamer CA, Shepherd DM. J Immunol. 2016 Apr 15;196(8):3217-25. doi: 10.4049/jimmunol.1502149. Review. PMID: 27044635
Acute Exposure to Crystalline Silica Reduces Macrophage Activation in Response to Bacterial Lipoproteins. Beamer GL, Seaver BP, Jessop F, Shepherd DM, Beamer CA. Front Immunol. 2016 Feb 15;7:49. doi: 10.3389/fimmu.2016.00049. eCollection 2016. PMID: 26913035
Role of the aryl hydrocarbon receptor (AhR) in lung inflammation. Beamer CA, Shepherd DM. Semin Immunopathol. 2013 Nov;35(6):693-704. doi: 10.1007/s00281-013-0391-7. Epub 2013 Aug 21. Review. PMID: 23963493
IL-1R signalling is critical for regulation of multi-walled carbon nanotubes-induced acute lung inflammation in C57Bl/6 mice. Girtsman TA, Beamer CA, Wu N, Buford M, Holian A. Nanotoxicology. 2014 Feb;8(1):17-27. doi: 10.3109/17435390.2012.744110. Epub 2012 Nov 14. PMID: 23094697
IL-33 mediates multi-walled carbon nanotube (MWCNT)-induced airway hyper-reactivity via the mobilization of innate helper cells in the lung. Beamer CA, Girtsman TA, Seaver BP, Finsaas KJ, Migliaccio CT, Perry VK, Rottman JB, Smith DE, Holian A. Nanotoxicology. 2013 Sep;7(6):1070-81. doi: 10.3109/17435390.2012.702230. Epub 2012 Jun 29. PMID: 22686327
Aryl hydrocarbon receptor (AhR) regulates silica-induced inflammation but not fibrosis. Beamer CA, Seaver BP, Shepherd DM. Toxicol Sci. 2012 Apr;126(2):554-68. doi: 10.1093/toxsci/kfs024. Epub 2012 Jan 23. PMID: 22273745
Indole-3-carbinol exerts sex-specific effects in murine colitis. J.A. Benson, C.A. Beamer, B.P. Seaver, and D.M. Shepherd. Eur J Inflamm. Sept-Dec. 10(3):336-346.
Inhibition of TLR ligand- and interferon gamma-induced murine microglial activation by Panax notoginseng. Beamer CA, Shepherd DM. J Neuroimmune Pharmacol. 2012 Jun;7(2):465-76. doi: 10.1007/s11481-011-9333-0. Epub 2011 Dec 21. PMID: 22183805
Innate immune processes are sufficient for driving silicosis in mice. Beamer CA, Migliaccio CT, Jessop F, Trapkus M, Yuan D, Holian A. J Leukoc Biol. 2010 Sep;88(3):547-57. doi: 10.1189/jlb.0210108. Epub 2010 Jun 24. PMID: 20576854
Critical role of MARCO in crystalline silica-induced pulmonary inflammation. Thakur SA, Beamer CA, Migliaccio CT, Holian A. Toxicol Sci. 2009 Apr;108(2):462-71. doi: 10.1093/toxsci/kfp011. Epub 2009 Jan 16. PMID: 19151164
Silica suppresses Toll-like receptor ligand-induced dendritic cell activation. Beamer CA, Holian A. FASEB J. 2008 Jun;22(6):2053-63. doi: 10.1096/fj.07-095299. Epub 2008 Jan 7. PMID: 18180331
Antigen-presenting cell population dynamics during murine silicosis. Beamer CA, Holian A. Am J Respir Cell Mol Biol. 2007 Dec;37(6):729-38. Epub 2007 Jul 19. PMID: 17641296
Motheaten (me/me) mice deficient in SHP-1 are less susceptible to focal cerebral ischemia. Beamer CA, Brooks DM, Lurie DI. J Neurosci Res. 2006 May 15;83(7):1220-30. PMID: 16528752
Scavenger receptor class A type I/II (CD204) null mice fail to develop fibrosis following silica exposure. Beamer CA, Holian A. Am J Physiol Lung Cell Mol Physiol. 2005 Aug;289(2):L186-95. Epub 2005 Apr 22. PMID: 15849212
Focal cerebral ischemia upregulates SHP-1 in reactive astrocytes in juvenile mice. Wishcamper CA, Brooks DM, Douglas Coffin J, Lurie DI. Brain Res. 2003 Jun 6;974(1-2):88-98. PMID: 12742627
Lack of the protein tyrosine phosphatase SHP-1 results in decreased numbers of glia within the motheaten (me/me) mouse brain. Wishcamper CA, Coffin JD, Lurie DI. J Comp Neurol. 2001 Dec 10;441(2):118-33. PMID: 11745639
2018-present Research Associate Professor the University of Montana, Center for Biomolecular Structure & Dynamics
2011-2018 Research Assistant Professor the University of Montana, Center for Biomolecular Structure & Dynamics
2007-2011 Research Associate the University of Montana, Biomedical & Pharmaceutical Sciences
2004-2007 NIEHS NRSA Postdoctoral Fellow the University of Montana, Center for Environmental Health Sciences
2002-2004 Postdoctoral Trainee the University of Montana, Center for Environmental Health Sciences
1999-2002 AFPE Pre-doctoral Fellow the University of Montana, Center for Structural Functional Neuroscience
1997-2002 Doctoral Student the University of Montana, Center for Structural Functional Neuroscience
1995-1997 Senior Thesis the Jackson Laboratory
2012-2013 The Malagharn Institute of Medical Research, Wellington New Zealand
2018 University of Montana Outstanding Performance Award
2012 University of Montana International Activities Visiting Scholar Award
2008 PArtnership for Comprehensive Equity Visiting Scholar Award
2006 Outstanding Platform Presentation Award at the 2006 PANWAT Annual Meeting
2006-2008 Pacific Northwest Association of Toxicologists Postdoctoral Representative
2006-2008 Immunotoxicology Specialty Section Postdoctoral Representative of SOT
2004-2007 NIEHS NRSA Post-doctoral Fellowship
2000-2001 Bertha Morton Pre-doctoral Fellowship
1999-2002 American Foundation for Pharmaceutical Education Pre-doctoral Fellowship