# Molecular and Functional Evaluation of NOTCH1 Deficient iPSC Derived Cardiomyocytes in Hypoplastic Left Heart Syndrome

> **NIH NIH K08** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $161,136

## Abstract

Project Summary/Abstract:
This proposal outlines a 5-year mentored career development plan as a physician-scientist for Anita Saraf, MD,
PhD as the principal investigator. Dr. Saraf is a tenure-track Assistant Professor at University of Pittsburgh
School of Medicine. She completed her graduate training through the Medical Scientist Training Program at
Baylor College of Medicine, Houston, TX with a Ph.D. in Bioengineering through the William Marsh Rice
University. Subsequently, she completed her residency and fellowship through the ABIM research pathway at
Emory University, Atlanta, GA and completed subspeciality training in Adult Congenital Heart Disease. Dr.
Saraf’s post-graduate research has focused on translational and basic science studies involving biomarker
profiles in single ventricle Fontan patients and understanding the effect of these biomarkers in cardiomyocytes
derived from induced pluripotent stem cells (iPSCs). Under the combined mentorship of Drs. Bernhard Kühn
and Toren Finkel (co-mentor), Dr. Saraf proposes to further her research skill-set in gene-editing and
cardiomyocyte physiology, with a long-term goal of establishing herself as a leader in translational and basic
science research in congenital heart disease.
In this proposal, Dr. Saraf investigates the role of NOTCH1 hypomorphic mutations in inducing arrhythmias
and heart failure in patient-derived and engineered cardiomyocytes from iPSCs. Using iPSCs from NOTCH1
hypomorphic patients with hypoplastic left heart syndrome (HLHS) and engineering similar hypomorphic
mutations in control iPSCs with CRISPR gene-editing, Dr. Saraf proposes the following objectives: (1)
Determine the influence of inflammatory cytokines (found to chronically elevated in univentricular patients) on
hypomorphic NOTCH1 cardiomyocytes and (2) Determine the influence of systemic pressures on hypomorphic
NOTCH1 cardiomyocytes, with respect to abnormal calcium-handling and contractility.
Given the lack of viable animal models for congenital heart disease, iPSC-derived cardiomyocytes together
with gene-editing technology provides a powerful platform to understand abnormalities in cardiomyocyte
physiology, discover novel targets for therapy, and create viable animal models with similar hypomorphic
mutations in the future. In addition to research training, Drs. Kühn, Finkel and Saraf have formulated a clear
timeline for career development involving publications, presentations at meetings and courses in leadership
that will transition Dr. Saraf to independence as a leader in this field.

## Key facts

- **NIH application ID:** 10794223
- **Project number:** 5K08HL161440-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Anita Saraf
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $161,136
- **Award type:** 5
- **Project period:** 2022-03-10 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10794223

## Citation

> US National Institutes of Health, RePORTER application 10794223, Molecular and Functional Evaluation of NOTCH1 Deficient iPSC Derived Cardiomyocytes in Hypoplastic Left Heart Syndrome (5K08HL161440-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10794223. Licensed CC0.

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