Andrij Holian

Professor, Director of Center for Environmental Health Science

Personal Summary

Dr. Holian attended Bowling Green State University, where in 1971 he received a B.S. in Chemistry. He received his Ph.D in Chemistry from Montana State University in 1975. Following positions at the University of Pennsylvania and Villanova University, he moved to Texas and joined the faculty of the University of Texas Health Science Center at Houston in 1984. During his tenure in Houston, Andrij rose to the rank of full professor and became the Director of Research for the Mickey Leland National Urban Air Toxics Research Center.  In July of 2000, he came to the University of Montana to serve as Director of the Center for Environmental Health Sciences in the Department of Biomedical and Pharmaceutical Sciences.

Field of Study

The primary focus of the laboratory is the elucidation of the molecular and cellular mechanisms of lung injury (inflammation and fibrosis) from a diverse array of agents including bleomycin, silica, asbestos, urban particles (metals), ozone, smoke particles and acrolein.  A common element in the actions of these agents is the apoptosis of alveolar macrophages.  We are investigating the role of apoptosis as an early and regulatory step in the etiology of lung disease and propose that preferential apoptosis of suppressor macrophages leads to the formation of an inflammatory state in the lung.  Current research areas are to characterize the mechanism(s) of macrophage induced apoptosis by the above agents and to test the hypothesis that ratios of different macrophage populations regulate inflammation and immune activity in the lung.  This work examines surface receptors, such as scavenger receptors, for the particles; signal transduction pathways (particularly tyrosine kinases and phosphatases, as well as transcription factors such as NF-kB) and caspases in macrophage apoptosis and characterization of human alveolar macrophage subpopulations.  In addition, our work is also evaluating the role of heme oxygenases and stress proteins as antioxidants and protection against apoptosis by oxidant stress.  These studies are being examined using traditional tools in a cell biology laboratory including transgenic and knockout mice and human subjects.  The goals of the studies are to develop strategies to identify subjects at greatest risk of developing lung injury, develop new methods to prevent or halt to progress of lung inflammation and evaluate the risk of human disease from environmentally and occupationally-derived toxic agents.

Selected Publications

Thakur SA, Beamer CA, Migliaccio CT, Holian A.  Critical role of MARCO in crystalline silica-induced pulmonary inflammation.  Tox Sci (in press).

Wells SM, Noonan C, Wells KM, Holian A, Wibbenmeyer LA. Effects of toxic gases: Methamphetamine inhalation. J Burn Care Res (in press).

Thakur SA, Hamilton RF, Pikkarainen T, Holian A.  Differential Binding of Inorganic Particles to MARCO.  Tox Sci 107(1):238-46, 2009.

Wells SM, Buford MC, Migliaccio C, Holian A. Elevated Asymmetric Dimethylarginine Alters ?Lung Function and Induces Collagen Deposition in Mice. Am J Respir Cell Mol Biol Am J Respir Cell Mol Biol 40(2):179-188, 2009.

Thakur SA, Hamilton RF, Holian A. Role of Scavenger Receptor A Family in Lung Inflammation from Exposure to Environmental Particles.  J Immunotoxicol  5:151-157, 2008.

Wells SM, Buford MC, Braseth SN, Hutchinson JD, Holian A. Acute Inhalation Exposure to Vaporized Methamphetamine Causes Lung Injury in Mice.  Inhalation Toxicol 20:829-38, 2008

Hamilton RF, Thakur SA, Holian, A. Silica Binding and Toxicity in Alveolar Macrophages. Free Radical Biol Med 44:1246-58, 2008.

Beamer C, Holian A. Silica suppresses Toll Like Receptor (TLR) Ligand-induced Dendritic cell Activation. The FASEB Journal 22:2053-63, 2008.

Migliaccio C, Buford M, Jessop F, Holian A.  The IL-4Ra Pathway in Macrophages and its Potential Role in Silica-Induced Pulmonary Fibrosis.  J Leuko Biol 83:630-9, 2008.

Latch JN, Hamilton RF, Holian A, Lam C-W, James JT. Toxicity of Lunar Dust Simulants to Alveolar Macrophages Isolated from Human Volunteers. Inhal Toxicol. 20(2):157-65, 2008.

Buford MC, Hamilton RF, Holian A. A Comparison of Dispersing Media for Various Engineered Carbon Nanoparticles.  Particle Fibre Toxicol Jul 27;4:6, 2007.

Beamer C, Holian A. Antigen Presenting Cell Population Dynamics During Murine Silicosis.  Am J Respir Cell Mol Biol 37:729-38, 2007.

Wells SA, Holian A. Asymmetric Dimethylarginine Induces Oxidative and Nitrosative Stress in Murine Lung Epithelial Cells. Am J Respir Cell Mol Biol 36:520-8, 2007.

Brown JM, Swindle EJ, Kushnir-Sukhov NM, Holian A, Metcalf DD.  Silica Directed Mast Cell Activation is Enhanced by Scavenger Receptors.  Am J Respir Cell Mol Biol 36:43-52, 2007.

Hamilton RF, Buford MC, Wood MB, Arnone B, Morandi MT, Holian A.  Engineered carbon nanoparticles alter macrophage immune function and initiate airway hyper-responsiveness in the BALB/c mouse model. Nanotoxicol 1:104-117, 2007.