# BLR&D Research Career Scientist Award Application

> **NIH VA IK6** · JOHN D DINGELL VA MEDICAL CENTER · 2022 · —

## Abstract

Inflammation is the body's attempt at self-protection to remove harmful stimuli and begin the healing process.
Chronic inflammation can eventually cause several diseases and conditions, including cancers, rheumatoid
arthritis, atherosclerosis, and plays a role in heart disease. The overarching goals of nominee’s research
involve elucidating molecular underpinnings of cell growth/survival and death/apoptosis with particular
reference cancer, atheroscleroscosis, and cardiovascular hypertension.
The American Cancer Society estimates highest percent of new cases and mortality resulting from lung and
breast cancers in females, while prostate and lung cancers account for highest percentage of new cases and
associated mortality among men. Overall incidence rates and mortality due to lung and breast cancers have
decreased over last decade partly due to advances in diagnosis and therapeutic modalities, particularly
targeted therapeutics for a number of cancers including the non-small cell lung cancers (NSCLCs). However,
adaptive genetic alterations and mutations in cancers contribute to therapy failures and relapses in clinic occur
that often result in emergence of resistant, hard to treat disease, and warrant development of new therapeutic
strategies to overcome drug resistance and improve therapeutic outcomes.
By utilizing a functional gene-knockout approach the nominee identified a novel, apoptosis inducing protein
termed CARP-1/CCAR1 (J. Biol. Chem. 278: 33422-33435, 2003). CARP-1 regulates apoptosis signaling
induced by diverse chemotherapeutics such as Adriamycin, Etoposide, and Gefitinib (reviewed by nominee in
Oncotarget 6(9): 6499-510, 2015). Following CARP-1 discovery, the nominee conducted a chemical-biological
approach to identify novel small molecule CARP-1 Functional Mimetic (CFMs) compounds (J. Biol. Chem. 286
(44): 38000-38017, 2011). CFMs inhibit growth diverse cancer cells including therapy-resistant triple-negative
breast cancers (TNBC) and non-small cell lung cancers (NSCLCs) in part by binding with CARP-1, causing
elevated levels of CARP-1 and apoptosis (Oncotarget, 2016, in press). The nominee’s long-term goal is to
elucidate molecular mechanisms of therapy resistance in cellular models of resistant TNBC and NSCLCs, and
utilize this knowledge to develop novel, safer and effective anti-cancer modalities. In this context CFMs or their
derivatives are anticipated to have clinical utility, and could provide novel means to develop future strategies
for effective treatment of TNBC, NSCLCs, and other cancers in the VA healthcare system and beyond.
Hypertension is a major health issue in the U.S., and the prevalence of atheros clerotic reno-vascular
hypertension is rising. Renal artery stenosis occurs in 28% of veterans undergoing cardiac catheterization with
a greater than 3-fold risk in those over age 65. Nonetheless, there is an alarming burden of cardiovascular and
renal morbidity and mortality with attendant increases in direct medical ...

## Key facts

- **NIH application ID:** 10293561
- **Project number:** 5IK6BX004015-05
- **Recipient organization:** JOHN D DINGELL VA MEDICAL CENTER
- **Principal Investigator:** Arun Kumar Rishi
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-10-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10293561

## Citation

> US National Institutes of Health, RePORTER application 10293561, BLR&D Research Career Scientist Award Application (5IK6BX004015-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10293561. Licensed CC0.

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