Faculty

Dr. Christopher Migliaccio

Dr. Chris Migliaccio Research Assistant Professor of Immunology
Email: christopher.migliaccio@umontana.edu
Phone: (406) 243-4529

Christopher Migliaccio arrived at The University of Montana in 2000 as a Post Doctoral Fellow. He earned a Ph.D. in Immunology at the University of California, Davis, CA in 2000 under the supervision of Drs. Judy Van de Water and M. Eric Gershwin. At the University of Montana, he received postdoctoral training in Molecular Virology under the guidance of Dr. Jack Nunberg at the Montana Biotechnology Center before moving to the Center for Environmental Health Sciences. At CEHS he completed further postdoctoral training in Immunotoxicology under the guidance of Dr. Andrij Holian. He was promoted to Research Assistant Professor in Immunology in 2008.

The Migliaccio lab: Dr. Christopher Migliaccio and Research Specialist Gini Porter

Research Interests
Publications
Grant Support
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Research Interests

The goal of my research program is to investigate the cellular and molecular mechanisms underlying regulation of the immune response. Currently, there are two primary lines of investigation. 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 the role of macrophage subsets in this process. Secondly, in collaboration with Dr. Tony Ward, we are studying how exposure to biomass smoke affects human health. Both of these studies are centered on understanding how the immune system functions in specific tissues in response to environmental contaminants.

Pulmonary Inflammation & Fibrosis

Pulmonary fibrosis is the result of some known and some unknown etiologies in the human condition. Likewise, there are multiple models of pulmonary fibrosis in the mouse. In the silicosis model, mice are exposed to the same fibrotic agent as humans and the end results are the same. Silicosis is an occupational lung disease resulting from the inhalation of silica particles over prolonged periods of time, which causes chronic inflammation and progressive pulmonary fibrosis. A major component of both the murine and human disease is the role of the pulmonary macrophage. Alveolar macrophages constitute a major innate immune component in the air spaces that have been shown to bind silica particles, resulting in altered functions. Silica has been noted in both in vivo and in vitro studies to result in cell death for macrophages; however, not all macrophages die following silica exposure. Currently there are multiple macrophage subpopulations that have been described in the lung, including the Th2-associated alternatively activated macrophage (aaMac). Recent data in our laboratory has shown a significant increase in the markers of the aaMac in the silicosis model, and Th2 immunity (i.e. IL-13) has been implicated in pulmonary fibrosis. An anti-apoptotic survival pathway in some cells, including macrophages, is the Akt pathway. This pathway is activated via insulin-like growth factor (IGF)-1. Multiple studies in both humans and mice have determined a key role for IGF-1 in fibrotic and remodeling pathologies. In addition to activating a survival pathway in both macrophages and fibroblasts, IGF-1 appears to play a role in the differentiation, proliferation, and activation of fibroblasts. Lastly, IGF-1 production from macrophages is induced by Th2 cytokines, but inhibited by Th1 (i.e. IFNg). Recent data in our laboratory has found a significant increase the IGF-1 protein in the lavage of silica-exposed mice. Current studies are focused on determining the role(s) of aaMac in silicosis, and the potential roles of IGF-1 in both survival of aaMac and fibroblasts, as well as the activation of fibroblasts to promote pulmonary fibrosis.

Health Effects of Exposure to Biomass Smoke

Inhalation of biomass (i.e. wood) smoke is a health issue in both the developed and developing world. Links between wood smoke exposure and infectious disease have been described in both animal experiments and human epidemiological studies. A variety of studies have found increases in acute respiratory illnesses (ARI) in children in homes where biomass burning is the primary method of cooking. Locally, individuals and communities are exposed episodically to biomass smoke through forest fires and land management burn practices. In addition, woodstoves are the primary source of residential home heating throughout the northern Rocky Mountain Region, contributing significant concentrations of wood smoke into both the ambient and indoor environments. In developing countries both heating and cooking can utilize open fires in the home resulting in extensive, chronic exposures. The key factor is in defining the level of exposure at which detrimental health effects occur. Recently our laboratory developed a system for a mouse model of wood smoke exposure. These studies are currently assessing the alterations of pulmonary macrophage populations and functions, and the role these changes play in the susceptibility to respiratory infection following exposure to wood smoke.

Recent Publications

Sarah E. Lacher, Corbin Johnson, Forrest Jessop, Andrij Holian, and Christopher T. Migliaccio. Murine Pulmonary Inflammation Model: A Comparative Study of Anesthesia and Instillation Methods. Inhalation Toxicology 2009. In press.

Andrij Holian, Allison Stock, Christopher Migliaccio, Curtis Noonan, and Tony Ward. Conference summary: International Biomass Smoke Health Effects (IBSHE). Inhalation Toxicology 2009. In press.

Christopher T. Migliaccio and Joe Mauderly. Toxicology and Animal Study Design: IBSHE Breakout Session. Inhalation Toxicology 2009. In press.

Thakur SA, Beamer CA, Migliaccio CT, Holian A. Critical Role of Marco in Crystalline Silica-Induced Pulmonary Inflammation. Toxicol Sci. 2009. 108:462-471. PMCID: PMC2664690.

Migliaccio, CT, MA Bergauff, CP Palmer, F Jessop, CW Noonan, and TJ Ward. Urinary Levoglucosan as a Biomarker of Wood Smoke Exposure: Observations in a Mouse Model and in Children. Environmental Health Perspectives 2009. 117(1):74-79. PMCID: 2627869.

Wells SM, Buford MC, Migliaccio, CT, and Holian A. Elevated Asymmetric Dimethylarginine Alters Lung Function and Induces Collagen Deposition in Mice. Am J Respir Cell Mol Biol. 2009. 40(2):179-88. PMCID: PMC2633140.

Migliaccio CT,Buford MC, Forrest Jessop, and Andrij Holian. The IL-4Ralpha pathway in macrophages and its potential role in silica-induced pulmonary fibrosis. Journal of Leukocyte Biology 2008, 83:630-639. PMID: 18056481.

CHAPTERS

Migliaccio, C.T. and Holian, A. Inflammatory Cells of the Lung: Macrophages. In: Comprehensive Toxicology, Editor Yost, G.S. 2009.

Migliaccio, C.T., J. Van de Water, S. Munoz, R.L. Coppel and M.E. Gershwin. The antigens of primary biliary cirrhosis: who are they and where do they come from? In: Decade of Autoimmunity, Editor Shoenfeld, Y., pp. 31-41.

Migliaccio, C.T., J. Van de Water, A.A. Ansari, R.L. Coppel and M.E. Gershwin. Antimitochondrial antibodies are the signature of primary biliary cirrhosis: deciphering the handwriting. In: Cholestatic Liver Diseases, Eds. Manns, M.P., J.L. Boyer, P.L.M. Jansen, J. Reichen, Kluwer Academic Publishers, pp. 239-247.

Grant Support

Ongoing Research Support
R01 ES-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

5P20RR017670-08 Holian, Andrij (PI) 09/30/02-05/31/12
National Institutes Of Health
Regulation of macrophage function by components of woodsmoke.
Role: Co-Investigator

Completed Research Support
F32 ES-013048 Migliaccio, Christopher (PI) 10/1/04 – 9/30/07
National Institute of Environmental Health Sciences (NIEHS)
The Role of Th2 Immunity in Late-stage silicosis
The goal of this proposal is to determine the role of Th2 immunity, specifically the alternatively activated macrophage, in the generation of silica-induced pulmonary fibrosis.
Role: PI

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