# Defining the Role of lnc-TECRL in Maladaptive Cardiac Remodeling

> **NIH NIH K08** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $167,724

## Abstract

Abstract
This proposal outlines a comprehensive 4-year training program to develop Veli K. Topkara, MD, MSc, an
Assistant Professor of Medicine at Columbia University, into an independent translational investigator. Dr.
Topkara is an advanced heart failure (HF) cardiologist whose long-term goal is to understand basic mechanisms
responsible for maladaptive cardiac remodeling with an emphasis on long non-coding RNAs (lncRNAs), in order
to improve outcomes of patients with heart failure. The career development plan and mentorship structure
proposed in this application are designed to fill specific educational and experiential gaps in Dr. Topkara’s
training, ensuring his maturation into an independent physician-scientist. His short-term career goals include: 1)
to develop skills in design and conduct of mechanistic translational research with a specific focus on lncRNA
biology, 2) to acquire expertise in generation of induced-pluripotent stem cell derived cardiomyocytes (iPS-CMs)
and gene editing technology, 3) to develop experience in computational and bioinformatics analysis of lncRNAs,
4) acquire skills in development and application of in vivo lncRNA knockdown strategies, and 5) to develop grant-
writing skills. The mentorship team represents a multidisciplinary group of individuals specifically chosen to
achieve PI's particular scientific and career development goals. At an institutional level, Columbia provides an
incredibly rich and supportive intellectual and collaborative research environment with ample resources available
for Dr. Topkara to successfully accomplish his research and career development goals. Through RNA
sequencing of failing human heart samples, Dr. Topkara identified 81 candidate lncRNAs that are significantly
dysregulated in HF. Based on (i) cardiac tissue enrichment in Genotype-Tissue Expression (GTEx) dataset, (ii)
reversibility with left ventricular assist device support, (iii) locus conservation in mouse, (iv) modulation during
cardiomyocyte hypertrophy; lnc-TECRL (lnc-Trans-2,3-Enoyl-CoA Reductase Like) was selected for structural
and functional characterization. Based on preliminary data, the main hypothesis of this proposal is that lnc-
TECRL mediates pathological cardiac hypertrophy through its interaction with chromatin modifying proteins and
activation of the hypertrophic gene program. The specific aims are to: 1) Determine mechanisms by which lnc-
TECRL mediates cardiomyocyte hypertrophy in vitro and 2) Investigate the therapeutic potential of lnc-TECRL
in prevention of maladaptive cardiac remodeling in vivo. To achieve these goals, the PI will utilize adult human
cardiomyocytes, human iPS-CMs, mature engineered human cardiac tissues, and mouse models which will
establish functional and therapeutic relevance of lnc-TECRL in cardiac remodeling. To understand mechanisms
by which lnc-TECRL mediates cardiac hypertrophy, state-of-art techniques including RNA pull-down, RNA-IP,
CHIP, domain mapping by deletion, ChiRP-s...

## Key facts

- **NIH application ID:** 10136705
- **Project number:** 5K08HL146964-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Veli Kemal Topkara
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $167,724
- **Award type:** 5
- **Project period:** 2019-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136705

## Citation

> US National Institutes of Health, RePORTER application 10136705, Defining the Role of lnc-TECRL in Maladaptive Cardiac Remodeling (5K08HL146964-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10136705. Licensed CC0.

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