# BLR&D Research Career Scientist Award Application

> **NIH VA IK6** · HARRY S. TRUMAN MEMORIAL VA HOSPITAL · 2020 · —

## Abstract

ABSTRACT
 Nearly 63 million people (20% of the US population) are eligible for VA benefits and services because
they are veterans, family members or survivors of veterans. Cardiovascular diseases (CVD) contribute to
significant morbidity and mortality of the military veterans and civilians (CDC/National Center for Health
Statistics). I have been associated with VA and non-VA funded clinician-scientists and basic researchers for
the past 20 years. I am also a VA funded investigator. The overall focus of my research as a VA funded
scientist is to investigate the causal role of inflammation, inflammatory cytokines and chemokines, and NF-κB
activation in CVD. Since inflammation is a critical component in the pathogenesis of CVD, and CVD are the
major contributing factors for morbidity and mortality within both military veteran and civilian populations of both
sexes, my studies are highly relevant to the VA mission. Furthermore, hypertension, diabetes, obesity and
smoking predispose veterans and civilians alike to CVD, my ongoing studies are timely and critical in further
understanding the pathophysiology of these chronic diseases. Using the most promising research strategies
and problem-solving approaches, my goal is to identify newer therapeutic targets in CVD. TRAF3 Interacting
Protein 2 (TRAF3IP2) is a cytoplasmic adapter molecule and an upstream regulator of at least three major
signal transduction pathways that are known to play a pathological role in ischemic cardiac diseases.
TRAF3IP2 activates IKK/NF-κB, JNK/AP-1 and p38 MAPK, and induces the expression of multiple cytokines
and chemokines with negative myocardial inotropic effects. It also regulates the expression of collagens and
MMPs. TRAF3IP2 is a critical intermediate in IL-17 signaling, another proinflammatory cytokine involved in
ischemic cardiac disease. Our preliminary results show that TRAF3IP2 also plays a role in IL-18 signaling. In
fact, we found that TRAF3IP2 binds the TIR (The Toll/Il-1 Receptor)-domain containing IL-18 receptor via
binding motifs that appear to be different from those responsible for TRAF3IP2/IL-17R binding. Bioinformatics
revealed that TRAF3IP2 could also associate with IL-1RacP (Interleukin 1 Receptor Accessory Protein), an IL-
1β receptor. We previously reported that TRAF3IP2 also plays a role in LPS/Toll-like receptor 4-mediated
cardiomyocyte contractile dysfunction, suggesting that targeting TRAF3IP2 could blunt IL-17, IL-18, IL-1 and
LPS signaling, all of which contribute causally to various cardiac pathologies, including cardiac ischemic injury.
Utilizing both in vivo (genetic and interventional) and in vitro (cardiomyocytes and cardiac fibroblasts) models,
my ongoing studies are examining the relationship between TRAF3IP2, inflammation and heart failure (HF) of
ischemic/non-ischemic origin in vivo and the underlying molecular mechanisms in vitro. My long-term goal is to
develop therapeutic strategies to inhibit TRAF3IP2 expression. Recently, we targete...

## Key facts

- **NIH application ID:** 9815464
- **Project number:** 5IK6BX004016-03
- **Recipient organization:** HARRY S. TRUMAN MEMORIAL VA HOSPITAL
- **Principal Investigator:** Chandrasekar Bysani
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9815464

## Citation

> US National Institutes of Health, RePORTER application 9815464, BLR&D Research Career Scientist Award Application (5IK6BX004016-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9815464. Licensed CC0.

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