# A 3D IN VITRO DISEASE MODEL OF ATRIAL CONDUCTION

> **NIH NIH UH3** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $723,616

## Abstract

PROJECT SUMMARY
The primary goal of this one-year competitive revision is to assess the potential of two novel therapeutics
(DS-iKL and DAPT) to mitigate the extrinsic and intrinsic cardiac effects of SARS-CoV-2, respectively. This is
important because, while acute respiratory distress is a major cause of morbidity and mortality of COVID-19,
the clinical disease caused by the SARS-CoV-2 coronavirus, it has more recently become widely evident that
other organ systems are involved including the heart and blood. For example, cardiac arrhythmias are a major
source of morbidity and mortality (44-60%) associated with COVID-19 disease, especially in individuals with
pre-existing cardiovascular disease in ICU settings. Two recent reports have indicated that 20-22% of
hospitalized patients with SARS-Cov-2 experience cardiac injury, and these patients suffer a staggering 50%
mortality rate, more than an order of magnitude greater than those patients without cardiac injury. Cardiac
arrythmias or myocardial injury are acutely life threatening and can be caused by a host of factors including co-
morbidities (e.g., hypertension), drugs, but also viral infection and systemic inflammation. In addition, a state
of hyper coagulation has also been described as a central feature of COVID-19, leading to blood clots that can
be life threatening as pulmonary emboli and right-sided cardiac failure. The specific aims of the project are to:
1) Assess the potential of DS-iKL as a novel therapeutic to mitigate the cardiac effects of SARS-CoV-2 initiated
cytokine storm (coagulation and vascular permeability) using a multi-organ microphysiological system of iPS-
derived human cardiomyocytes and vascular endothelium; 2) Assess the potential of the Notch signaling
inhibitor, DAPT, on viral infectivity and thus intrinsic cardiac effects of SARS-CoV-2, in an organotypic tissue
slice model of healthy and predisposed adult human cardiac tissue. We anticipate a rich data set resulting
from these experiments that should demonstrate the exciting potential of DS-iKL and DAPT to mitigate the
extrinsic and intrinsic cardiac effects of SARS-CoV-2. The research plan will also produce a path to in vivo
human studies to accelerate translation. Finally, the potential impact of DS-iKL and DAPT to mitigate the
effects of SARS-CoV-2 are likely to also be applicable to other inflammatory and infectious diseases that share
similar disease etiology.

## Key facts

- **NIH application ID:** 10166441
- **Project number:** 3UH3HL141800-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** David Terry Curiel
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $723,616
- **Award type:** 3
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166441

## Citation

> US National Institutes of Health, RePORTER application 10166441, A 3D IN VITRO DISEASE MODEL OF ATRIAL CONDUCTION (3UH3HL141800-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10166441. Licensed CC0.

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