Investigator, Center for Toxicology
Professor, BIO5 Institute
Professor, Public Health
Professor, Public Health
Dr. Lantz is Professor of Molecular and Cellular Medicine, and Professor, Division of Community, Environment and Policy at the University of Arizona. He is currently the Associate Department Head and has served in interim positions as the Department Head of Cellular and Molecular Medicine and as Associate Vice President for Research of the University of Arizona. He is also currently Deputy Director of the Southwest Environmental Health Science Center (SWEHSC), an NIEHS Core Center of Excellence at the University of Arizona and Deputy Director of the University of Arizona Superfund Research Program.
Dr. Lantz received his B.S. in Physics from Juniata College in 1970 and his doctorate in Physiology and Biophysics from West Virginia University in 1975. After postdoctoral research fellowships at Rockefeller University and Emory University, Dr. Lantz took a position as Assistant Professor of Anatomy at West Virginia University in 1981. In 1987, Dr. Lantz moved to the University of Arizona where he holds his current academic position.
Dr. Lantz has served as the Director of the Cellular Imaging Core of the SWEHSC since the Center was originally funded in 1994. Part of Dr. Lantz’s duties as Deputy Director of SWEHSC is to oversee the Core Facilities funded by the Center. These include genomics, proteomics, imaging, and in the past, synthetic chemistry. Dr. Lantz has also served as the Chair of the Biotechnology Imaging Users Committee at the University of Arizona has chaired and co-authored a White Paper outlining the needs and vision for state-of-the-art light microscopic imaging on campus. Dr. Lantz, therefore, has demonstrated and extensive administrative experience especially related to oversight and management of Core Facilities.
Dr. Lantz’s research has utilized these core facilities along with an inhalation core facility developed by Dr. Lantz and his colleagues at the University of Arizona. Over the past 30 years, Dr. Lantz has concentrated his research in the area of pulmonary toxicology. During that time he has nearly 30 publications where inhalation of toxicants has been the route of exposure for gases, liquids and particulates. Toxicants have included inhalation exposures to complex smoke from fires, cigarette smoke, jet fuel, bacterial products and arsenic. In a number of these publications he has tested intervention strategies with the aim of reducing lung injury. Some of his most recent research has focused on the effects of inhalation of arsenic containing dusts on lung inflammation and the role of Nrf2 activation in protection from this exposure.
More recently, Dr. Lantz has extended his studies into an analysis of arsenic-induced alterations in pulmonary function and biomarker expression in children ages 6-12. Dr. Lantz’s research has been funded from the National Institutes of Health (NIEHS, NCI) and from the USEPA. Dr. Lantz is the author of over 90 peer reviewed manuscripts. Dr. Lantz received the Career Achievement Award from the Inhalation and Respiratory Specialty Section of the Society of Toxicology in 2011 in recognition of his work in inhalation and respiratory toxicology.
Exposure to environmental toxicants alters lung structure and function and leads to chronic lung disease, including cancer. Current investigations are examining the effects of exposure to environmentally relevant doses of arsenic and uranium. Arsenic is a naturally occurring metalloid found in water, soil and air. Exposure to inorganic arsenic occurs worldwide, including the southwestern United States and Mexico, through environmental (contaminated drinking water, air, food and domestic fuel sources) and occupational exposures (smelting industries, pesticide production). Epidemiologic studies have associated arsenic exposure with an increased risk of multiple human cancers including lung, skin, bladder, kidney, liver and stomach cancers. In addition arsenic exposures are associated with non-malignant diseases, such as peripheral vascular disease, diabetes and chronic obstructive pulmonary disease.
Our current research is focusing on two models to examine the effects of arsenic in the lung. One model relies on exposure to arsenic during lung development, both in utero and postnatally. We have previously shown that exposure of pregnant female rats to arsenic in their drinking water until embryonic day 18 resulted in altered expression of extracellular matrix genes. In addition, genes involved in vascular development also appear to be targets. We are currently continuing exposure to arsenic after birth. In addition to cancer endpoints, arsenic exposures can also lead to noncancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic were found to alter airway reactivity to methacholine challenge. Alterations in air reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Alterations in matrix gene expression andairway smooth muscle were correlated with alterations in structure and lung function. Dietary folate supplementation reduced the arsenic induced functional alterations. This model system demonstrates that developmental exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary function in the adults and that dietary intervention strategies may be useful in reducing the adverse health effects caused by in utero and postnatal arsenic exposures.
A second model relies on chronic 4 to 8 week exposure of adult mice to arsenic in drinking water. We have evaluated alterations in mRNA and protein levels from animals exposed to 50 ppb. Again, extracellular matrix genes are among the classes of genes that are altered by this exposure. In addition, alterations in elastin and collagen deposition are being determined to link gene expression changes with phenotypic structural alterations in the lung. Data are also being analyzed using an annotated data base to identify pathways and transcriptional regulators that may be affected by the exposure to arsenic.
Research is also on going to identify protein alterations in lung lining fluid as biomarkers of exposure and effect prior to the development of disease following exposure to arsenic. This study uses the technology of proteomics to evaluate and identify biomarkers of chronic environmental exposure to arsenic by evaluating large numbers of proteins simultaneously. We are comparing alterations in protein expression in exposed human populations in Arizona and Mexico, human cell lines, and in vivo rodent studies. Patterns of alterations in protein expression, both common and unique to these different test systems, are being identified.
Finally, we are evaluating the chemical genotoxicity of uranium. In addition to its radioactive effects, uranium may also have adverse health effects because of its interactions with cellular macromolecules. We have found that uranium does directly interact with DNA and appears to form cross links. DNA damage caused by uranium does not appear to be mediated by induction of oxidative stress. Studies to define the interactions of uranium with DNA and proteins in the lung are continuing.
Diane Stearns, PhD., Northern Arizona University: genotoxicity of uranium
Jefferey Burgess, MD, MS, MPH. College of Public Health: arsenic biomarkers in human populations
Scott Boitano, PhD. Arizona Respiratory Center: arsenic effects of human lung cells
Mercedes Montenegro, PhD. ITSON, Obregon, Sonora, Mexico: arsenic biomarkers in human populations
- WVU Foundation Predoctoral Fellowship, 1970-1973
- Individual NIH Postdoctoral fellowship, 1975-1977
- NIOSH-CDC Special Emphasis Research Career Award, 1984-1987
- Deputy Director, Southwest Environmental Health Science Center, 1999 - present
- Society of Toxicology
- American Association of Anatomists
- American Public Health Association