Celine Beamer - Research Associate
- Department of Biomedical and Pharmaceutical Sciences, University of Montana 2007 - Present
- Postdoctoral Training Center for Environmental Health Sciences University of Montana 2002 - Present
- Doctoral Training University of Montana
- Ph.D. 2002
Research Interests
The goal of my research program is to investigate the cellular and molecular mechanisms underlying regulation of the immune response. There are several lines of investigation currently underway in the laboratory. First, in collaboration with Dr. Andrij Holian, we are studying how the immune system regulates inflammation and fibrosis associated with environmental particulates in the respiratory tract and central nervous system (CNS). In conjunction with this, we are elucidating the mechanisms responsible for the ability of inhaled crystalline particles to alter susceptibility to mycobacterium tuberculosis (TB) infections in humans. Second, in collaboration with Dr. David Shepherd, we are studying how the immune response within the inflamed CNS may be modulated by treatment with nutraceutical extracts in models of neuroinflammation such as multiple sclerosis (MS). Both of these studies are centered on understanding how the immune systems functions in specific tissues in response to environmental contaminants.
Respiratory Inflammation & Fibrosis
Regulation of the immune response in the lung is a complex process which involves maintaining tolerance to endogenous self-antigens and innocuous particulates, while preserving the capability to appropriately respond to invading microorganisms and pathogens. Respiratory injury perturbs immune homeostasis by inducing an initial systemic inflammatory response, followed by a compensatory anti-inflammatory response. These opposing actions represent the behaviors of the innate and adaptive immune systems. The relative importance of the altered reactivity of these two systems in immune dysfunction observed in respiratory diseases is not yet defined, and remains a subject of some controversy. Consequently, defining the cellular and molecular events involved in regulating inflammation and fibrosis will result in more effective diagnosis and treatment of respiratory diseases.
Although significant efforts have been made through industrial hygiene standards to control ambient dust in the workplace, respiratory inflammation and fibrosis remain prevalent health problems throughout the world. Intrapulmonary deposition of silica, asbestos, desert sand, and other environmental particulates results in an inflammatory response which progresses to interstitial fibrosis, as well as other systemic immune deficits. Currently, we are examining the how the interactions between these types of airborne particulates and antigen presenting cells (APC), and the subsequent interactions between APC and other immune cells influences inflammation, fibrosis, and other systemic immune deficits. Similarly, we are determining the cellular and molecular mechanisms whereby exposure to airborne particulates (e.g. crystalline silica) alters susceptibility to bacterial infections (e.g. TB). Studying how the normal immune system becomes dysregulated is critical for development of improved therapies for both diseases.
CNS Inflammation & Microglial Activation
The central nervous system (CNS) is susceptible to inflammatory and autoimmune diseases; although the healthy organ is considered immunologically dormant. Growing evidence implicates inflammation as underlying the pathogenesis of a diverse array of CNS pathologies including stroke, meningitis, Alzheimer’s disease, AIDS dementia, and multiple sclerosis (MS). Immune cells are critical not only in the initial phase of the inflammatory response, but also in the repair processes following injury. Microglia (MÖ) are the resident immuno-competent myeloid-derived cells and are the largest population of potential antigen presenting cells. Under normal conditions, MÖ reside in the tissue, are quiescent, and display little to no phagocytic activity until the integrity of the CNS is challenged by environmental pathogens. Traditionally, MÖ activation is a normal and potentially beneficial response to CNS injury; however, in many disease states this activation contributes to, if not causes, neurodegeneration via pro-inflammatory cytokines and cytotoxic factors, such as nitric oxide (NO), glutamate, and TNFa . Therefore, understanding the regulation of and limiting MÖ activation in response to environmental pathogens is an important therapeutic strategy for limiting CNS disease progression. Currently, we are investigating how MÖ activation influences CNS inflammation in response to challenge by environmental pathogens using both in vitro and in vivo models of CNS disease.
Nutraceutical Modulation of Immune Function
Current therapies for debilitating immune diseases are based on treatments that non-specifically suppress the immune system. Such therapeutics are potent and have far reaching adverse consequences for the patient including impaired ability to fight off common infections, a hampering of the natural induction of tolerance, and considerable expense. Although these immune therapies are widely used, their efficacy in controlling disease progression is only modest. Therefore, more effective agents with a favorable safety profile are vigorously sought.
Herbal medicine has recently drawn much attention due to its potential inhibitory effects on CNS inflammatory responses. Because of its wide range of pharmacological effects, ginseng has been used in traditional Chinese medicine for more than 5 thousand years as both a tonic and a haemostatic agent. Although the ability of ginseng to modulate inflammatory and allergic processes has been documented within the peripheral immune system, to date there is a shortage of studies examining ginseng’s ability to modulate inflammatory conditions within the CNS. Using an in vitro system, we found that exposure of toll like receptor (TLR) ligand-stimulated MÖ to an ethanolic extract of Panax Notoginseng (NotoGTM) reduces MÖ activation in a dose-dependent and ligand-specific manner. Currently, we are investigating how NotoG regulates CNS inflammation.
Publications
Celine A Beamer and David M. Shepherd. (2008). Inhibition of TLR ligand- and Interferon gamma-induced murine microglial activation by Panax Notoginseng. Pending.
Celine A Beamer and Andrij Holian. (2008) Silica suppresses Toll Like Receptor ligand-induced dendritic cell activation. FASEB J. Jun;22(6):2053-63.
Celine A Beamer and Andrij Holian. (2007) Antigen presenting cell population dynamics during murine silicosis. Am J Respir Cell Mol Biol. Dec; 37(6):729-38.
Celine A Beamer, Diane M Brooks, and Diana I Lurie. (2006). Motheaten (me/me) mice deficient in SHP-1 are less susceptible to focal cerebral ischemia. J Neurosci Res. 2006 May 15;83(7):1220-30.
Celine A Beamer and Andrij Holian. (2005). Scavenger receptor class A type I/II (CD204) null mice fail to develop fibrosis following silica exposure. Am J Physiol Lung Cell Mol Physiol. Aug; 289(2):L186-95.
Celine A Wishcamper, Diane M Brooks, J. Douglas Coffin, and Diana I Lurie. (2003) Focal cerebral ischemia upregulates SHP-1 in non-proliferating reactive astrocytes. Brain Res. Jun 6; 974(1-2):88-98.
Celine A. Wishcamper, J. Douglas Coffin, and Diana I. Lurie. (2001) Lack of the protein tyrosine phosphatase SHP-1 results in decreased numbers of glia within the motheaten (me/me) mouse brain. J Comp Neurol. Dec 10;441(2):118-33.
Grant Support
Ongoing Research Support
R01 E S-015294, Holian, Andrij (PI), 12/01/06 - 11/30/11
National Institute of Environmental Health Sciences (NIEHS)
Defining the roles of macrophage subsets and NK lymphocytes in silicosis.
The aims of this proposal are to test the central hypothesis that activated macrophages with NK lymphocytes constitute steps that are sufficient to result in the development of chronic inflammation progressing to
silicosis.
Role: Co-Investigator
Completed Research Support
F32 ES-013044, Beamer, Celine (PI), 07/1/04 – 06/30/07
National Institute of Environmental Health Sciences (NIEHS)
Akt activation sustains silica induced inflammation
This aims of this project are to test the central hypothesis that silica induced production of TNFa sustains inflammation by activating the Akt signaling pathway in alveolar macrophages.
Role: PI
Contact Information
Celine A Beamer, Ph.D.
The University of Montana
Dept. of Biomedical and Pharmaceutical Sciences
Center for Environmental Health Sciences
32 Campus Dr. Skaggs 285A
Missoula, MT 59801
Phone: 406-243-4947
Fax: 406-243-2807
e-mail: celine.beamer@umontana.edu