Faculty Research

Department of Environmental and Occupational Health faculty members primarily focus their research efforts on respiratory and cardiovascular toxicology, free radical biochemical toxicology, computational and risk assessment approaches to environmental health, and molecular mechanisms of genomic instability associated with cancer and aging.

SALLY WENZEL - Department Chair

Our laboratory has focused on understanding both the subtypes of human asthma and the combination of environmental and genetic factors which drive them.  Research has focused on the role of airway epithelial cells in human disease, given the position of these cells to link the environment with the host.  Work encompasses use of large epidemiologic/research databases, including those both local and national, to define patient characteristics and relationships to environmental triggers, but also to include studies of specific human immunology, both in human samples and model systems.  Current pathways of interest include those related to environmental and innate lung oxidative stress, as well as their intersections with inflammation, mucins and cell death pathways.

***Dr. Wenzel has been chosen to be the American Thoracic Society (ATS) 2021 Amberson Lecturer at this year’s ATS Conference (May 14th-19th). The Amberson Lecture recognizes exemplary professionalism, collegiality and citizenship through mentorship and leadership in the ATS community. The Amberson Lecturer is an individual with a career of major lifetime contributions to clinical or basic pulmonary research and/or clinical practice. The Lecture is given in honor of James Burns Amberson, an international authority on chest disease and tuberculosis.***
 

ANDREW AMOSCATO

My research focuses on understanding the role that lipid oxidation/lipid-protein interactions play as physiological signaling mechanisms in a variety of cell death processes including, but not limited to, apoptosis, ferroptosis and necroptosis. A significant portion of my work utilizes lipidomic, proteomic and metabolomic mass spectrometric methods of analysis to address a variety of physiological and pathological processes in cells and tissues.
 

AARON BARCHOWSKY

The primary focus of current research is investigating the cellular and molecular mechanisms underlying human blood vessel and lung diseases caused by environmental exposures to metals and chronic changes in redox status. In vivo and cell cultured-based studies focus on the molecular pathology and etiology of vascular disease caused by chronic exposure to low levels of arsenic in drinking water. The cell signaling pathways that mediate arsenic stimulated pathogenic phenotypic changes in endothelial cells are being investigated. Additional studies examine the molecular signaling mechanisms mediating gene induction and silencing in airway epithelial cells exposed to chromium. The objective of these studies is to identify the pathways through which inhaled chromium aggravates lung injury from infections and exposure to other metals.
 

KIFLAI BIEN

Currently, we are working in the area of cellular signaling mechanisms of lung injury with emphasis on acute lung injury induced by particulate air pollutants such as nickel. In particular, we will investigate the role of TGF a- and TGF b-regulated signaling pathways in nickel-induced acute lung injury. Molecular and tissue culture-based studies will focus on identification and characterization of key signaling proteins, transcription factors, and promoter sequences that modulate susceptibility to nickel-induced acute lung injury. These studies, combined with animal studies, will advance our understanding of the genetic determinants of acute lung injury.
 

NESTA BORTEY-SAM

My research focuses on understanding many aspects of environmental toxicology, including both the fate, bioaccumulation, phase I & II metabolism, excretion, and effects of toxic substances such as metals. Other research areas include isotope ratios and epidemiological studies investigating the association between exposure to Pb, As, and PAHs, and occurrences of chronic kidney disease and respiratory outcomes.
 

HAIDER DAR

My work is aimed at understanding the genetically programmed cell death mechanisms (ferroptosis/necroptosis) of host and their regulation in the context of the injury imposed on lungs and other tissues (gut and brain cortex) by different insults- environmental, chemical, physical or biological. Deciphering the mechanisms of cell death programs is important for the development of new drugs and diagnostic procedures. At present the focus is to explore ferroptosis at the intersection of host-pathogen (Pseudomonas aeruginosa) cross talk particularly in immune compromised patients within hospital environment, in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).
 

BERTHONY DESLOUCHES

The primary goal of my laboratory is to develop peptide-based antimicrobial therapeutics against multidrug-resistant bacteria. A secondary objective is to establish how the environment influences the composition of the host microbiota and the resulting health consequences.

Antibiotic resistance constitutes a global health crisis, which threatens to reverse many advances in the field of medicine. In that regard, cationic antimicrobial peptides (AMPs) are a class of antimicrobial agents that are very promising therapeutics against multidrug-resistant (MDR) bacteria-related infections because of their ability to directly disrupt bacterial membranes and their lower propensity to invoke selection of resistance compared to conventional antibiotics, regardless of resistance to traditional antibiotics. However, cationic peptides present several limitations related to their lack of activity in some types of biological environments (e.g., divalent cations, blood) and susceptibility to protease digestion. While sequence optimization or de novo engineering can help overcome some of these limitations, AMP design is currently done mainly by trial and error based on the principle of cationic amphipathicity. Thus, the future of this promising class of peptides depends on the ability to design AMPs for specific applications by dissecting the AMP functional motifs to uncouple their dual properties of antimicrobial activity and host toxicity. This can be accomplished by establishing a general framework for cationic peptide design, based on iterative structure-function (spectrum of activity, drug affinity, bacterial killing and resistance mechanisms, and toxicity to mammalian cells) relationship to minimize peptide length required for low or absence of toxicity to mammalian cells and high therapeutic index. Data are usually streamlined to elucidate therapeutic mechanisms by dissecting the structural determinants of selectivity against MDR bacteria compared to mammalian cells.

Our approach to the microbiota in health and disease is to examine how the environment (including drugs and toxicants) impacts host defense and inflammatory diseases in relationship to changes in the microbiome. This project is not yet initiated.
 

PETER DI

Our laboratory is interested in investigating effects of environmental stress such as toxic chemicals and microorganisms on airway epithelial cell differentiation and lung diseases. One of our current research projects is focused on elucidating the molecular mechanisms that regulate the interaction between airway epithelial cells and exposure to environmental insults such as TCDD and tobacco smoke. We are also interested in how environmental agents affect host defense mechanism, especially airway secretion and infection that relates to pulmonary disease. The ultimate goal of our laboratory is to develop new potential biomarkers for early detection of preneoplastic lesions that is caused by environmental exposure, as well as for the development of novel treatment strategies against toxicant-induced respiratory pathogenesis.
 

JIM FABISIAK

My overall research mission is dedicated to the investigation of cellular mechanisms by which various environmental agents, particularly those that affect the lung, perturb cell physiology, and, thus, contribute to organ dysfunction during toxicity. Only by understanding the cellular and molecular mechanisms of toxin action can effective chemopreventive and therapeutic strategies be designed. Of primary current interest is the role of oxidative stress, not only as a mediator of cellular damage, but also as a physiologic signaling mechanism that can dictate numerous cellular responses.
 

NICHOLAS FITZ

Neurodegenerative diseases are complex multifactorial diseases with identified genetic determinants along with environmental influences and life-style choices. Our lab is focused on understating how gene-environment interactions modify the molecular pathogenesis of Alzheimer’s disease, specifically examining changes in brain cholesterol and lipid transport. A major focus is uncovering the role of APOE and TREM2 in glial function, neuroinflammation and amyloid pathology. We use broad approaches with primary glial culture, transgenic mouse models, and Alzheimer’s disease patient samples, including: CHIPseq, RNAseq, single cell RNAseq, lipidomics, in vivo microdialysis, and complex imaging.
 

VALERIAN KAGAN

Kagan’s laboratory and Center for Free Radical and Antioxidant Health has been studying redox mechanisms of physiological processes in cells and tissues as well as their aberrant changes caused by exposure to environmental factors and disease conditions. The major focus of this work is on phospholipids and their role in signaling. The Lab has developed highly sensitive and specific LC-MS based protocols for the detection, identification and quantitative analysis of oxidatively modified lipids.  With this technological advancement, the major efforts are directed towards understanding and deciphering the signaling language of peroxidized phospholipids. Among the most advanced areas of research are studies of phospholipid signals in programs of regulated death such as apoptosis, necroptosis and ferroptosis. This work resulted in the discovery of new mechanisms of cell death in acute brain injury, acute radiation syndrome, pulmonary diseases (including ARDS, asthma and bacterial pathogen/host interactions in the lung), organ transplantation. Another aspect of the current work is related to decoding of mechanisms of lipid reprogramming of innate immune cells in tumor microenvironment leading to immunosuppression of myeloid cells in cancer.  Unearthing of new enzymatic mechanisms of redox phospholipid signaling leads to the design and development of new therapeutic modalities. This work is also going on in the Lab.
 

OLEKSANDR KAPRALOV

I am studying the role of lipid peroxidation in the control of cell death with focus on understanding of the role of enzymatic lipid peroxidation in regulation of ferroptosis and apoptosis.
 

PHOUTHONE KEOHAVONG - Associate Professor Emeritus

My research focuses on understanding the molecular mechanisms of mutagenesis and the mutational pathways that link environmental chemicals to cancer. We have developed and applied new molecular approaches to determine the mutational spectra for potential carcinogens. Thus, our studies include identification of the types, positions, and frequencies of mutations after treatment with the chemical agent.
 

RADA KOLDAMOVA

Our laboratory uses broad approaches to dissect regulatory networks and to explore the role of lipid-associated genes and proteins in molecular pathogenesis of Alzheimer’s disease.
 

ILIYA LEFTEROV

Current projects relate to genetically modified mouse models of Alzheimer’s disease (AD) and cholesterol metabolism. A particular focus is on liver X receptors (LXR). Their regulatory function in the brain in health and disease is being approached using complex transgenic mouse models of altered lipid metabolism. Behavioral phenotyping and histopathology are used to reveal clues of LXR-controlled regulatory networks in the brain. Age-dependent and disease-related changes in immediate early genes (IEG) response to environmental factors is the second major research theme. Molecular, pharmacological, and genetic approaches; gene profiling; and chromatin immunoprecipitation followed by massive parallel sequencing (ChIP-seq) in intact animal models of AD are being used to assess IEG-controlled signaling pathways. AD pathogenesis in those models is assessed in the context of gene-environment interactions genome-wide using high-throughput genomic and epigenetic tools, diet, and dietary manipulations.
 

GEORGE LEIKAUF

I am investigating the functional genomics of acute lung injury, asthma, and chronic obstructive pulmonary disease. Molecular mechanisms by which air pollutants exacerbate or cause lung diseases are being studied by various strategies including genetic linkage and microarray analyses and transgenic/gene-targeted murine systems. A major research interest is uncovering the genetic basis of increased susceptibility to pulmonary epithelial injury and repair. In addition, recent studies are examining transcriptional regulation of molecular targets (e.g., surfactant proteins) altered by exposure to ozone, aldehydes, and particulate matter.
 

MAUREEN LICHTVELD - Dean - Graduate School of Public Health

Dean Lichtveld’s national and global environmental health research examines the cumulative impact of chemical and non-chemical stressors on communities facing environmental health threats, disasters including pandemics and health disparities.
 

KYONGNYON NAM

My research focuses are to understand the information of genome-wide epigenetic changes and identification of genetic marker involved in Alzheimer’s diseases for improved diagnosis. Alzheimer’s disease is a complex disease caused by a combination of genetic, lifestyle, and environmental factors including diet, arsenic exposure, and sex. Our laboratory generates genome-wide transcriptional and epigenetic profiling in response to various risk factors from different cell types, Alzheimer's disease mice models, and human brain using ChIP-seq, RNA-seq, and single cell RNA-seq.
 

PATTY OPRESKO

I am studying molecular mechanisms of genomic instability associated with cancer and aging with an initial focus on telomeric DNA, genetic and environmental factors that alter rates of telomere attrition, mechanisms of telomere loss in the progeroid disorder Werner syndrome, roles of the Werner syndrome protein in repair and replication of telomeric DNA, and cellular pathways that repair and restore damaged telomeric DNA.

***Dr. Opresko is the 2020 recipient of the Merrill J. Egorin Excellence in Scientific Leadership Award. This award honors a faculty member that exemplifies scientific passion and scholastic dedication.***
 

LUIS ORTIZ

My focus is the study of mechanisms of lung injury and repair in response to particles and the biology of bone marrow-derived Mesenchymal stem cells and their use during lung injury and repair.
 

LINDA PEARCE

I am conducting studies of the interactions of reactive oxygen, nitrogen, and radiation with mitochondria, particularly using microelectrodes and magnetic circular dichroism spectroscopy.
 

JAMES PETERSON

My research focuses on (1) amelioration of acute cyanide toxicity, (2) the cytotoxic effects of nitric-oxide-derived oxidants, (3) ionizing radiation-induced mechanisms of cell death, and (4) application of magneto-optical spectroscopy to the study of biological systems.
 

BRUCE PITT

My laboratory efforts are directed toward original studies on the molecular and cellular biology of the lung. To date, this work has focused primarily on the role of oxidants and nitric oxide in affecting pulmonary endothelial and vascular smooth muscle cell function. Isolated primary cell cultures, genetically modified murine models, and somatic gene transfer to lung have been used as model systems to identify the role of partially reduced oxygen and nitrogen species in the response of the lung to stress and injury.
 

WINNIE TANG

My current research focuses on deciphering how environmental pollutants/allergen and dietary factors alter the epigenome via DNA de/methylation and induce chromatin remodeling, leading to complex diseases like asthma, cardiovascular diseases, sleep apnea and cancer. My long-term goal is to apply innovative and promising epigenetic approaches to understand the underlying mechanisms by which epigenetic changes may contribute to common diseases. Our findings may lead to the development of improved preventive measures and therapeutic strategies to reduce the burden of chronic diseases. Also, translating our scientific findings into human may provide proper disease management and lifetime recommendations to the public.
 

VLADIMIR TYURIN

My goal is to elucidate the molecular mechanisms through which lipid metabolites regulate cellular membrane structures as well as membrane-bound complexes, particularly under conditions of oxidative/nitrosative stress.
 

YULIA TYURINA

My primary research is concerned with the role of free radical reactions and, more specifically, the role of lipid peroxidation in apoptosis.
 

JINMING ZHAO

My research has been focused on airway epithelium physiology and cell biology in respiratory disease, particularly the role of Th2/15LO1/autophagy/ferroptosis as related to asthma pathogenesis. 15-Lipoxygenase 1 (15LO1) is one of the several key enzymes in arachidonic acid (AA) metabolism. We were the first to identify that 15LO1 competes with and displaces Raf-1 from its binding with Phosphatidylethanolamine-binding protein 1 (PEBP1), which plays a critical role in asthma pathogenesis. Our ultimate goal is to identify the modification of 15LO1/PEBP1 interaction as a novel therapeutic approach to dampen inflammatory processes in asthma and other diseases.
 

XIUXIA ZHOU

My current research has been focused on the role of N-glycosylation/sialylation on airway physiology and pathology in asthma. Particularly, studies are performed to elucidate the role of Th2/ST6GAL1/MUC4B-ErbB2 axis in regulating epithelium wound repair through regulating cell proliferation, differentiation, senescence and cell death pathways, as well as their interactions under Th1 environment. The research aims to identify novel targets for treatment of severe asthma.
 

Recent EOH Publications

Lagged Association of Ambient Outdoor Air Pollutants with Asthma-Related Emergency Department Visits within the Pittsburgh Region 

Lagged Association of Ambient Outdoor Air Pollutants with Asthma-Related Emergency Department Visits within the Pittsburgh Region

Brandy M. Byrwa-Hill, Arvind Venkat, Albert A. Presto, Judith R. Rager, Deborah Gentile, and Evelyn Talbott find an association between O 3 exposure in children and NO 2 and CO exposure in adults and asthma-related ED visits within the greater Pittsburgh area.  (12/06/2020)
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Wenzel in Lancet: Intersection of biology and therapeutics: type 2 targeted therapeutics for adult asthma 

Wenzel in Lancet: Intersection of biology and therapeutics: type 2 targeted therapeutics for adult asthma

In a recent article published in the Lancet, EOH Chair Sally Wenzel found that "the emergence of type 2 biologics for the treatment of severe asthma is a welcomed and much needed advance in the management of patients with asthma. Although a cure for asthma remains elusive, many patients with severe... (02/04/2020)

Engineered Cationic Antimicrobial Peptides (eCAPs) to Combat Multidrug-Resistant Bacteria http://ow.ly/1oaO50A1WfW

Redox lipidomics technology: Looking for a needle in a haystack http://ow.ly/dvi150zHwxK

Redox lipid reprogramming commands susceptibility of macrophages and microglia to ferroptotic death http://ow.ly/pjHD50zcBjL

Mechanisms of ultrafine particle-induced respiratory health effects ow.ly/2b1r50yZCGZ

Arsenic Stimulates Myoblast Mitochondrial EGFR to Impair Myogenesis ow.ly/MoSq50yPdEr

Detection of brain specific cardiolipins in plasma after experimental pediatric head injury ow.ly/MTpX50yAgUX

Redox lipid reprogramming commands susceptibility of macrophages and microglia to ferroptotic death ow.ly/MQH950yAgSB

Determination and Quantification of Bacterial Virulent Gene Expression Using Quantitative Real-Time PCR ncbi.nlm.nih.gov/pubmed/31989555

Analysis of Telomere Length and Aberrations by Quantitative FISH. ow.ly/U64R50ycgQq

Molecular Analysis of Mutations in the Human HPRT Gene - ow.ly/IcvI50ycgKM

Intersection of biology and therapeutics: type 2 targeted therapeutics for adult asthma: sciencedirect.com/science/articl… #Lancet #Asthma

Redox phospholipidomics of enzymatically generated oxygenated phospholipids as specific signals of programmed cell death ow.ly/MTnA50xWgBw

APOE2 orchestrated differences in transcriptomic and lipidomic profiles of postmortem AD brain ow.ly/lYzF50xWgmB