# BLR&D Research Career Scientist Application

> **NIH VA IK6** · OMAHA VA  MEDICAL CENTER · 2024 · —

## Abstract

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 (Fun...

## Key facts

- **NIH application ID:** 10881724
- **Project number:** 5IK6BX005962-03
- **Recipient organization:** OMAHA VA  MEDICAL CENTER
- **Principal Investigator:** Todd A Wyatt
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881724

## Citation

> US National Institutes of Health, RePORTER application 10881724, BLR&D Research Career Scientist Application (5IK6BX005962-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10881724. Licensed CC0.

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