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Andrij Holian
Professor
Director, Center for Environmental Health Sciences

Phone: (406) 243-4018

Email: andrij.holian@umontana.edu

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.

RESEARCH STATEMENT
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.
KEY PUBLICATIONS

Latch JN, Hamilton RF, Holian A, Lam C-W, James JT. Toxicity of Lunar Dust Simulants to Alveolar  Macrophages Isolated from Human Volunteers.  Inhalation Toxicol (in press).

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 (in press).

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 (in press).

Hamilton RF, Thakur SA, Mayfair JK, Holian A.  MARCO mediates silica uptake and toxicity in alveolar macrophages from C57BL/6 mice. J Biol Chem 281:34218-26, 2006.

Ward T, Hart J, Noonan C, Spear T,  Holian A, Getman M, Webber J. Trees as reservoirs for amphibole fibers in Libby, Montana. Sci Total Environ 367:460-465, 2006.

Dmitrienko, NP, Holian A. Role of interaction of metabolism paths of formaldehyde and nitrogen oxide in the mechanism of their toxic effect.  2. Toxic effect of nitrogen oxide.  Ukr Biokhim Zh 77:5-23, 2005.

Dmitrienko NP, Holian A. Effect of the interaction of formaldehyde and nitric oxide metabolism pathways in mechanism of their toxic action. I. Exo- and endogenous sources of formaldehyde and nitric oxide. Toxic action of formaldehyde. Ukr Biokhim Zh 77:22-31, 2005.

Brown JM, Schwanke CM, Pershouse MA, Pfau JC, Holian A.  Effects of rottlerin on Silica-exacerbated systemic autoimmune disease in New Zealand mixed mice.  Am J Physiol Lung Cell Mol Physiol 289:L990-998, 2005.

Schumpert JC, Noonan C, Sylvester J, Vanek D, Ward T, Holian A.  Patterns of asthma symptoms and perceptions of risk from wildfire smoke in rural western Montana.  Int J Occup Environ Health. 12:52-58, 2006.

Beamer C, Holian A. CD204-null mice fail to develop fibrosis following silica exposure. Am J Physiol Lung Cell Mol Physiol 289:L186-95, 2005.

Migliaccio, CT, Hamilton, RF, Holian A. Increase in a distinct pulmonary macrophage subset possessing an antigen-presenting cell phenotype and in vitro APC activity following silica exposure.  Toxicol App Pharmacol 205:168-176, 2005.

Scheider JC, Card GL, Pfau JC, Holian A. Air pollution particulate PM1648 causes oxidative stress in RAW 264.7 macrophage leading to production of prostaglandin E2, a potential Th2 mediator.  Inhalation Toxicol 17:1-7, 2005.

Brown, JM, Pfau, JC, Pershouse MA, Holian A.  Silica, Apoptosis and Autoimmunity.  J Immunotoxicol 1:177-187, 2004.

Hassani, M, Brown, JM, Morandi, MT, Holian, A.  Particulate Matter Immunomodulatory Effects on Autoantibody Development in New Zealand Mixed Mice.  J Immunotoxicol 1:95-102, 2004.

Hamilton RF, Parsley E, Holian A. Alveolar Macrophages from Systemic Sclerosis Patients: Evidence for IL-4-Mediated Phenotype Changes.  Am J Physiol Lung Cell Mol Physiol 286:L1202-9, 2004.

Murr LE, Bang JJ, Lopez DA, Guerrero PA, Esquivel EV, Choudhuri AR, Subramanya M, Morandi M, Holian A. Carbon nanotubes and nanocrystals in methane combustion and the environmental implications. J Materials Sci 39: 2199-2204, 2004.

Brown JM, Pfau JC, Holian A.  Immunoglobulin and Lymphocyte Responses Following Silica Exposure in New Zealand Mixed Mice.  Inhalation Toxicol 16: 133-139, 2004.