Andrij Holian

Main profile

Dr.

Andrij

Holian

Director, Center for Environmental Health Sciences

Professor

Academic Profile

Academic Profile

Personal Statement

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. He is also the Scientific Director of the CEHS Inhalation and Pulmonary Physiology Core.

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. Our laboratory has a pulmonary disease research emphasis with expertise in macrophage biology and immune disregulation. The goals of the studies are to develop strategies to identify subjects at greatest risk of developing lung injury, develop new methods/pharmacologic tools to prevent or halt to progress of lung inflammation and evaluate the risk of human disease from environmentally and occupationally-derived toxic agents. Listed below are brief summaries of ongoing projects.

Nanomaterials Toxicity:

As reported by the National Academy of Sciences, the development of nanomaterials is outpacing the evaluation of potential risk that these materials may be causing to the environment and human health. Our laboratory has ongoing projects funded by NIH and NSF to determine what health effects could be caused by nanomaterials, their mechanism(s) of action and what characteristics of nanomaterials are most likely to lead to toxic effects. We have established that carbon nanotubes and titanium nanowires cause lung inflammation, granulomas and fibrosis. In vitro studies have shown that macrophage cell lines are poor models for primary macrophages where nanowires induce macrophage apoptosis and necrosis. Both in vivo and in vitro studies indicate that the order of potency is long nanowires > short nanowires >> nanospheres with respect to toxicity and lung injury. This outcome suggested that something other than surface chemistry is responsible for unique toxicity of nanowires and current research supports the hypothesis that the toxicity is directly proportional to lysosomal disruption. Current research is examining the mechanisms responsible for membrane recognition, lysosomal disruption, design of safe nanomaterials and pharmacological intervention to limit lung pathologies resulting from exposures to these materials.

Silica and Scavenger Receptors:

We have utilized crystalline silica as a model toxic particulate to study the mechanisms involved in the development of lung fibrosis that may be caused by various agents or unknown in the case of idiopathic lung fibrosis. Since no effective therapeutic approaches are currently in practice this presents an important challenge. Ongoing NIH-funded projects are examining:

1. the role of signaling mechanisms in inflammasome activation in macrophages and therapeutic interventions using in vivo models in the development of lung fibrosis as well as autoimmune disease;
2. contribution of other immune cells to disease pathology; and
3. the protective role that the scavenger receptor MARCO plays in preventing lung inflammation.

Asbestos Research:

Similar to silica, asbestos is known to cause lung fibrosis and appears to enhance autoimmune diseases. There are a number of different forms of asbestos with amphiboles forms considered more toxic than chrysotile, which is a serpentine fiber. Over the past few years interest has increased in a somewhat different form of amphibole that contaminated vermiculite mined in Libby, MT. This Libby amphibole has been responsible for a high frequency of occupationally linked cases of asbestos related diseases and environmentally associated cases. Not only is the composition different, but also the sizes of the fibers are smaller. These differences as well as the real world diseases that exist in Libby pose significant challenges and needs to identify mechanisms of action of these fibers in disease causation in order to develop therapeutic intervention. Current studies are examining the roles of fiber size in toxicity and pathological outcomes as well as mechanisms of toxicity.

Methamphetamine:

While it has been well recognized that methamphetamine is a highly addictive drug our studies have shown that smoking methamphetamine causes acute lung injury as well as severe constriction of blood vesicles in the heart. These outcomes may explain the anecdotal and published observations that children taken from homes, where methamphetamine exposures have occurred, have acute respiratory distress while users develop cardiovascular complications. Our CDC funded research program has shown that relatively low exposures increase airway hyper-reactivity as well as cardiovascular changes in murine models. Our current focus is developing information on mechanisms to explain these events with the goal of providing caregivers and first responders new information on dealing with children and others who have been exposed to methamphetamine smoke.

Biomass smoke:

Many studies have now shown that exposure to respirable particulate matter (PM2.5) causes a variety of health effects and that living in an environment with cleaner air increases life expectancy. There is increasing evidence that maternal exposures to particulate matter may lead to epigenetic changes. Since exposures to biomass smoke can be very high in indoor environments in homes with wood stoves (in rural settings as well as in developing countries) and during wildfire events our focus is on potential epigenetic changes from biomass smoke exposures that may predispose children towards development of asthma.

Recent Publications

Innate immune processes are sufficient for driving silicosis in mice.
Beamer CA, Migliaccio C, Jessop F, Trapkus M, Yuan D, Holian A.
J Leuko Biol 88(3)547-557, 2010.  PMID: 20576854

Nonpulmonary outcomes of asbestos exposure.
Bunderson-Schelvan M, Pfau JC, Holian A.
J Toxicol Environ Health, Part B (in press).

COPD is Associated with a Macrophage Scavenger Receptor (MSR1) Gene Sequence Variation.
Ohar JA, Hamilton RF Jr, Zheng S, Sadeghnejad A, Sterling DA, Xu J, Meyers DA, Bleecker ER, Holian A.
Chest. 2010 Jan 15. [Epub ahead of print]. PMID: 20081102.

Conference summary: International Biomass Smoke Health Effects (IBSHE).
Holian A, Stock A, Migliaccio C, Noonan C, Ward T.
Inhal Toxicol. 2010 Feb;22(2):91-3. PMID: 20044882

Particle length dependent titanium dioxide nanomaterials toxicity and bioactivity.
Hamilton RF, Wu N, Porter D, Buford M, Wolfarth M, Holian A.
Particle Fibre Toxicol 6(1):35, 2009. PMID:20043844

Role of the Serotonergic System in Reduced Pulmonary Function Following Exposure to Methamphetamine.
Wells SM, Buford MC, Porter VM, Brunell HL, Bunderson-Schelvan M, Nevin AB, Cardozo-Pelaez F, Holian A.
Am J Respir Cell Mol Biol. 2009 Jun 18. [Epub ahead of print]. P MID: 19541843.

Murine pulmonary inflammation model: a comparative study of anesthesia and instillation methods.
Lacher S, Johnson C, Jessop F, Holian A, Migliaccio M.
Inhal Toxicol. 2010 Jan;22(1):77-83. NIHMSID: 169062.

Modified low density lipoproteins binding requires a lysine cluster region in the murine macrophage scavenger receptor class A type II.
Levya FJ, Pershouse MA, Holian A.
Mol Biol Rep. 2009 Sep 23. [Epub ahead of print]. PMID: 19774489

Effects of toxic gases: Methamphetamine inhalation.
Wells SM, Noonan C, Wells KM, Holian A, Wibbenmeyer LA.
J Burn Care Res 30(1):152-4, 2009. PMID: 19060736.

Critical role of MARCO in crystalline silica-induced pulmonary inflammation.
Thakur SA, Beamer CA, Migliaccio CT, Holian A.
Tox Sci 108(2):462-471, 2009. PMCID: PMC2664690.

Differential Binding of Inorganic Particles to MARCO.
Thakur SA, Hamilton RF, Pikkarainen T, Holian A.
Tox Sci 107(1):238-46, 2009. PMCID: PMC2735421.

Elevated Asymmetric Dimethylarginine Alters Lung Function and Induces Collagen Deposition in Mice.
Wells SM, Buford MC, Migliaccio C, Holian A.
Am J Respir Cell Mol Biol Am J Respir Cell Mol Biol 40(2):179-188, 2009. PMCID: PMC2633140.

Role of Scavenger Receptor A Family in Lung Inflammation from Exposure to Environmental Particles.
Thakur SA, Hamilton RF, Holian A.
J Immunotoxicol 5:151-157, 2008. PMID: 18569385.

Acute Inhalation Exposure to Vaporized Methamphetamine Causes Lung Injury in Mice.
Wells SM, Buford MC, Braseth SN, Hutchinson JD, Holian A.
Inhalation Toxicol 20:829-38, 2008. PCMID: PMC2753821.

Silica Binding and Toxicity in Alveolar Macrophages.
Hamilton RF, Thakur SA, Holian, A.
Free Radical Biol Med 44:1246-58, 2008. PMCID: 2680955.

Silica suppresses Toll Like Receptor (TLR) Ligand-induced Dendritic cell Activation.
Beamer C, Holian A.
The FASEB Journal 22:2053-63, 2008. PMID: 18180331.

The IL-4Ra Pathway in Macrophages and its Potential Role in Silica-Induced Pulmonary Fibrosis.
Migliaccio C, Buford M, Jessop F, Holian A.
J Leuko Biol 83:630-9, 2008. PMID: 18056481.

Toxicity of Lunar Dust Simulants to Alveolar Macrophages Isolated from Human Volunteers.
Latch JN, Hamilton RF, Holian A, Lam C-W, James JT.
Inhal Toxicol. 20(2):157-65, 2008. PMID: 18236230.