Chris Migliaccio

Main profile

Dr.

Chris

Migliaccio

Research Assistant Professor

Academic Profile

Academic Profile

Personal Statement

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.

 

 

Research Statement

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

Innate immune processes are sufficient for driving silicosis in mice.
Beamer CA, Migliaccio CT, Jessop F, Trapkus M, Yuan D, Holian A.
J Leukocyte Biology 2010. PMCID: PMC2924603.

Urinary Levoglucosan as a Biomarker for Wood Smoke: Results of Human Exposure Studies.
Bergauff, M, Ward T, Noonan C, Migliaccio C, Simpson C, Evanoski A, Palmer C.
Journal of Exp Sci and Environ Epidem 2010. PMID: 19707249.

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. Inhal Toxicol. 2010 Jan;22(1):77-83. NIHMSID: 169062.

Christopher T. Migliaccio and Joe Mauderly. Toxicology and Animal Study Design: IBSHE Breakout Session. Inhal Toxicol. 2010 Feb;22(2):104-7. PMID: 20041808.

Andrij Holian, Allison Stock, Christopher Migliaccio, Curtis Noonan, and Tony Ward.  Conference summary: International Biomass Smoke Health Effects (IBSHE). Inhal Toxicol. 2010 Feb;22(2):91-3. PMID : 20044882

Bergauff MA, Ward TJ, Noonan CW, Migliaccio CT, Simpson CD, Evanoski AR, Palmer CP. Urinary levoglucosan as a biomarker of wood smoke: Results of human exposure studies. J Expo Sci Environ Epidemiol. 2009 Aug 26. [Epub ahead of print]. NIHMSID: 168348.

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.