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Principal Investigator: Todd A Wyatt
Organization: OMAHA VA MEDICAL CENTER
Fiscal Year: 2022
Funding agency: Veterans Affairs
My primary research interests address chronic inflammatory lung disease, and the impact that behavioral and
environmental exposures play in the compromise of lung innate defense against pathologic lung infections and
injury. Utilizing pre-clinical mouse models and state-of-the-art molecular, biochemical, and cellular approaches,
I collaborate closely with pulmonologists who practice at the VA to conduct relevant pre-clinical research that
can be used to address current clinical concerns. I translate my findings to Veterans’ health using a well-
characterized human lung cell and tissue biobank obtained from our lung transplant program. We have an
existing cohort of Veterans with rural/agricultural occupational exposures to conduct relevant studies to our
service region. There are 3 major research projects currently underway that impact veterans’ health:
Malondialdehyde-acetaldehyde adducts and lung injury. Alcohol abuse causing increased susceptibility to
pneumonia has been known for over 200 years. Because the majority (>90%) individuals misusing alcohol
smoke cigarettes, we study the combination lung injury effects of both cigarettes and alcohol. We identified that
the lungs represent a unique environment for the formation of stable malondialdehyde-acetaldehyde protein
adducts (MAA adducts), but only under conditions of combined cigarette smoke and alcohol exposure. These
MAA adducts cause airway epithelial cell cilia slowing and impair the innate pathogen clearance from the lung.
Surfactant protein D (SPD) is a major lung protein that gets adducted when lung aldehyde concentrations are
elevated during combined smoke and alcohol exposure and SPD-MAA adducts are detected in the lung only in
drinkers who also smoke, leading to alterations in innate lung defense. (Funded by BX003635). Veterans-
centric COVID-19 research. The pathogenesis of the SARS-CoV-2 virus and clinical outcomes from COVID
19 are far worse in individuals with certain pre-existing conditions and those of advanced age. It is essential to
the health of Veterans to fully define which at-risk conditions particularly impact them and their unique needs to
empower clinical preventive care during this and future viral pandemics. Old age and alcohol misuse are
associated with cilia dysfunction. SPD has been documented to specifically bind to and neutralize the Spike
protein of coronavirus. We hypothesize that altered innate lung defense at the level of mucociliary clearance,
anti-microbial surfactants, and viral receptor function will negatively impact susceptibility and pathogenesis of
SARS-CoV-2, placing Veterans particularly in harm’s way. We are currently identifying differences in SARS-
CoV-2 infection responses between normal airway epithelium and lung macrophages and those cells collected
from individuals with COPD, with alcohol use disorder, or of old age. Defining the modalities of risk will
empower clinicians to make informed clinical preventive care decisions for Veterans (Funded by BX005413).
Agricultural organic dust-mediated lung injury. VISN 23 encompasses a region responsible for the largest
agricultural output in the nation. In collaboration with Omaha VA physician scientists, we have built a cohort of
Veterans with agricultural exposures to explore the impact of organic dusts on chronic lung inflammatory injury.
Using established mouse models, we have identified the therapeutic impact of IL-10 on lung repair from dust-
mediated injury. We are currently defining the mechanisms of action through an active NIOSH R01 study and
the Central States Center for Agricultural safety and Health (Funded by OH010162). With these innovative
research programs, I have been able to provide training and mentoring to many undergraduates, graduate
students, fellows, junior scientists and physicians at the Omaha VAMC and affiliated University of Nebraska
Medical Center (UNMC). Our efforts to investigate the underlying mechanisms and identify targets for
pulmonary disease have brought together physician scientists and basic scientists at the Omaha VA medical
center and UNMC, which has led to the development of a VA-funded live-animal microCT Core facility, which I
supervise and is the only such instrument in Omaha.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><65+ years old><ADAM-17><Acetaldehyde><Address><Adenosine Cyclic Monophosphate-Dependent Protein Kinases><Admission><Admission activity><Age><Aged 65 and Over><Agriculture><Alcohol Chemical Class><Alcohol Drinking><Alcohol abuse><Alcohol consumption><Alcohols><Aldehydes><Animal Model><Animal Models and Related Studies><Animals><Area><Armed Forces Personnel><Award><Bacterial Infections><Behavioral><Binding><Biochemical><Biological Markers><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Body Tissues><COPD><COVID-19><COVID-19 infection><COVID-19 virus><COVID19><COVID19 infection><COVID19 virus><CSIF><CSIF-10><CV-19><CV19><Caring><Cell Body><Cell Locomotion><Cell Migration><Cell Movement><Cells><Cellular Migration><Cellular Motility><Chronic><Chronic Obstruction Pulmonary Disease><Chronic Obstructive Lung Disease><Chronic Obstructive Pulmonary Disease><Chronic lung disease><Cigarette><Cilia><Clinical><CoV S protein><CoV glycoprotein S><CoV spike glycoprotein><CoV spike protein><CoV-2><CoV2><Collaborations><Core Facility><Coronavirus glycoprotein S><Coronavirus spike protein><Cyclic AMP-Dependent Protein Kinases><Cytokine Synthesis Inhibitory Factor><Development><Dust><Dysfunction><EXTMR><Elderly><Environment><Environmental Exposure><Epithelial Cells><EtOH abuse><EtOH drinking><EtOH use><Ethanal><Exposure to><Extramural><Extramural Activities><Functional disorder><Funding><Future><Grant><Health><Health Care Costs><Health Care Systems><Health Costs><Healthcare><Healthcare Costs><Healthcare Systems><Heavy Drinking><History><Hospitals><Human><IL-10><IL10><IL10A><Impairment><Individual><Inflammation><Inflammatory><Injury><Innate Immunity><Interleukin 10 Precursor><Interleukin-10><Laboratories><Life><Lung><Lung Grafting><Lung Protein D><Lung Respiratory System><Lung Transplantation><Lung damage><Lung diseases><Lung infections><Malonaldehyde><Malondialdehyde><Malonylaldehyde><Malonyldialdehyde><Manuscripts><Marrow Neutrophil><Mediating><Medical center><Mentors><Methodology><Military><Military Personnel><Modality><Modern Man><Molecular><Molecular Interaction><Morbidity><Morbidity - disease rate><Motility><Mucociliary Clearance><Mucociliary Transport><Mφ><Native Immunity><Natural Immunity><Nebraska><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Non-Specific Immunity><Nonspecific Immunity><Occupational Exposure><Outcome><Output><PKA><PKC epsilon><Pathogenesis><Pathologic><Peer Review><Physicians><Physiopathology><Play><Pneumonia><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Predisposition><Preventative care><Preventive care><Propanedial><Protein Kinase A><Proteins><Pulmonary Diseases><Pulmonary Disorder><Pulmonary Graft><Pulmonary Surfactant Protein D><Pulmonary Surfactant-Associated Protein D><Pulmonary Transplant><Pulmonary Transplantation><R-Series Research Projects><R01 Mechanism><R01 Program><RSV infection><Recording of previous events><Regulation><Research><Research Grants><Research Project Grants><Research Projects><Respiratory Epithelium><Respiratory Syncytial Virus Infections><Risk><Role><Rural><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV-2 pathogenesis><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SP-D><Safety><Sampling><Savings><Science><Scientist><Seminal><Services><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Smoke><Smoker><Smoking><Source><Structure of respiratory epithelium><Substance abuse problem><Supervision><Surfactant Protein D><Surfactant-Associated Glycoprotein D><Susceptibility><System><TNF-alpha converting enzyme><TNF-α converting enzyme><Therapeutic><Time><Tissues><Training><Translating><Universities><Veterans><Viral><Viral Diseases><Viral Receptor><Virus><Virus Diseases><Virus Receptors><Work><Wuhan coronavirus><X-ray microtomography><Xray microtomography><abuse of substances><adduct><advanced age><age 65 and greater><age 65 and older><aged 65 and greater><aged ≥65><ages><agricultural><agricultural center><airway epithelium><airway epithelium inflammation><airway inflammation><alcohol co-abuse><alcohol exposed><alcohol exposure><alcohol ingestion><alcohol intake><alcohol misuse><alcohol problem><alcohol product use><alcohol response><alcohol use><alcohol use disorder><alcoholic beverage consumption><alcoholic drink intake><anti-microbial><antimicrobial><bacteria infection><bacterial disease><bio-markers><biobank><biologic marker><biomarker><biorepository><cAMP-Dependent Protein Kinases><career><cell motility><chronic inflammatory lung disease><chronic pulmonary disease><cigarette smoke><cigarette smoke exposure><cohort><corona virus disease 2019><coronavirus S protein><coronavirus disease 2019><coronavirus disease 2019 infection><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus spike glycoprotein><cost><desensitization><developmental><digital><disease of the lung><disease risk><disorder of the lung><disorder risk><drink heavily><elders><ethanol abuse><ethanol consumption><ethanol drinking><ethanol exposed><ethanol exposure><ethanol ingestion><ethanol intake><ethanol misuse><ethanol product use><ethanol response><ethanol use><ethanol use disorder><ex-smoker><excessive alcohol consumption><excessive alcohol ingestion><excessive alcohol intake><excessive drinking><excessive ethanol ingestion><experience><exposed to alcohol><exposed to ethanol><exposure to alcohol><exposure to cigarette smoke><exposure to ethanol><extreme drinking><former smoker><geriatric><graduate student><hCoV19><hazardous alcohol use><health care><heavy alcohol use><human old age (65+)><improved><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><injuries><innovate><innovation><innovative><instrument><interest><late life><later life><lung disorder><lung injury><lung repair><lung tissue repair><lung transplant><macrophage><micro CT><micro computed tomography><microCT><microtomography><military member><military population><military trauma><military veteran><model of animal><model organism><mortality><mouse model><murine model><nCoV2><neutrophil><old age><older adult><older person><pandemic><pandemic disease><pathogen><pathophysiology><pneumonia therapy><pneumonia treatment><pre-clinical><pre-clinical research><preclinical><preclinical research><problem alcohol use><problem drinking><problematic alcohol consumption><problematic alcohol use><programs><protein kinase C epsilon><pulmonary><pulmonary damage><pulmonary infections><pulmonary injury><pulmonary repair><pulmonary tissue damage><pulmonary tissue injury><receptor function><respiratory inflammation><respiratory tract inflammation><response><response to alcohol><response to ethanol><senior citizen><service member><severe acute respiratory syndrome coronavirus 2 pathogenesis><sex><social role><substance abuse><surfactant><treat pneumonia><tumor necrosis factor alpha convertase><tumor necrosis factor-alpha converting enzyme><undergrad><undergraduate><undergraduate student><unhealthy alcohol use><veteran population><viral infection><virus infection><virus-induced disease><workplace exposure>