# BLRD Research Career Scientist Award Application

> **NIH VA IK6** · JAMES A. HALEY VA MEDICAL CENTER · 2021 · —

## Abstract

The PI, Mark S. Kindy, Ph.D., has been studying the mechanisms and pathways associated with a number of
neurological and neurodegenerative disorders. These include, Alzheimer’s disease (AD), stroke, Parkinson’s
disease (PD), traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE), spinal cord injury (SCI),
among others. All of these disorders are afflictions that are present in the VA population and contribute
significantly to the overall health of the Veterans. The overarching goal is to understand the mechanisms
involved in the disease processes and to develop therapeutic approaches to treat them. I have three basic areas
of research that we focus on. The first program is centered around stroke and the impact of negative vascular
health factors (such as: obesity, diabetes, age, salt sensitivity hyperlipidemia, and hypertensivity) on the
induction of reactive oxygen species (ROS) production and activation of the inflammation (inflammasome). We
have shown that aged animals with the risk factors have worse outcomes and recovery is exacerbated due to
the presence of both systemic and neuroinflammation. The generation of better clinical models of stroke to test
these risk factors and health disparities following injury. Studies using low-density lipoprotein receptor (ldlr)
deficient mice with and without high fat diet are being used to study the impact of oxidized phospholipids (OxPLs)
on stroke outcomes. Mice expressing OxPL antibodies will be tested for protection from stroke. Finally, we are
examining the impact of chronic kidney disease, left ventricular hypertrophy and FGF23 on stroke and stroke
outcomes. Mice with targeted deletion of the fgfr4 gene or overexpression of the FGF23 are being examined for
stroke outcomes. These studies will better capture the true nature of veterans and civilians who have a stroke
and provide a better approach to treating the disease. A second line of research focuses on the role of serum
amyloid A (SAA) proteins in the pathogenesis of stroke. Recent studies have implicated SAAs in innate immunity
and various disorders, however the precise mechanism eludes us. SAAs are elevated following stroke (cerebral
ischemia) and TBI, and our studies show that SAA increases the cytokine interleukin-1 (IL-1), which is
mediated by Nod-like receptor protein 3 (NLRP3) inflammasome, cathepsin B and caspase-1 and may play a
role in the pathogenesis of neurological disorders. Using transgenic and gene deleted mice as well as AAV
expressing constructs we are evaluating the impact of SAA on stroke and other neurological diseases. Another
line of research focuses on serum amyloid P component (SAP), which is found in all amyloids and studies have
suggested that it plays an integral role in the formation, progression, and maintenance of the amyloid disease
processes. The amyloid diseases include: AD, PD (tau, -synuclein, TDP-43), tauopathies, CTE, ALS (SOD1,
TDP-43, C9ORF72), systemic amyloids (AA, TTR, amylin), Huntingt...

## Key facts

- **NIH application ID:** 10118026
- **Project number:** 5IK6BX005239-02
- **Recipient organization:** JAMES A. HALEY VA MEDICAL CENTER
- **Principal Investigator:** MARK S. KINDY
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10118026

## Citation

> US National Institutes of Health, RePORTER application 10118026, BLRD Research Career Scientist Award Application (5IK6BX005239-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10118026. Licensed CC0.

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