# Genetic Risk Underlying Pediatric Critical Illness

> **NIH NIH K08** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $254,727

## Abstract

Project Summary/Abstract
Children rarely become critically ill. I hypothesize that genetic risk contributes to unexpected pediatric critical
illness. Identifying risk groups allows for clinical stratification and targeted therapies, but these benefits can
only be realized if risk is known. This proposal will uncover the monogenic (i.e., single gene), polygenic (i.e.,
many genes), and pharmacogenomic (i.e., genetic effect on drug response) risks contributing to pediatric
critical illness. In Aim 1, I apply innovative gene-network discovery methods to uncover monogenic risk for viral
respiratory failure, the most common cause of pediatric intensive care unit admission. In Aim 2, I will assess
the contribution of polygenic risk to common pediatric intensive care unit morbidities (viral respiratory failure,
venous thromboembolism, acute kidney injury). In Aim 3, I will assess pharmacogenomic risk detected by
exome and genome sequencing. This K08 will uncover genetic risk in critically ill children which will inform
future multi-center genetic association studies and clinical trials to improve care in the pediatric intensive care
unit. Candidate: Scientifically, I have a PhD in neuroscience and completed a post-doctoral fellowship in
human genetics. Clinically, I am an attending physician in pediatric critical care medicine. There is a need for
physician-scientists who can identify unusual disease presentations and uncover novel genetic risk. There is
limited application of precision medicine in the pediatric intensive care unit, and I am well positioned to identify
opportunities and investigate applications. My goal is to develop an independent research program focused on
“the genomics of pediatric critical illness”. During the K08 training period, I will: (1) Refine expertise in gene
network discovery, (2) Develop expertise in the novel application of polygenic risk scores to children with
critical illness, (3) Develop expertise in pharmacogenomic analysis of exomes and genomes, (4) Become
proficient in the Ethical, Legal, and Social Implications (ELSI) of genomics, and (5) Transition to independence.
Environment: To guide and support my research and training goals, I have assembled a strong mentorship
team of experts in genetics and medicine (Dr Gharavi, Mentor and Dr. Chung, Advisor), polygenic risk scores
(Dr. Kiryluk, Advisor), pharmacogenomics (Dr. Jobanputra, Advisor and Dr. Chung, Advisor), statistical
genetics (Dr. Ionita-Laza, Advisor), allergy and inborn errors of immunity (Dr. Orange, Advisor), renal genetics
(Dr. Gharavi, Mentor and Dr. Kiryluk, Advisor), and Equity and ELSI research (Dr. Sabatello, Advisor). The
research will be conducted at Columbia University Irving Medical Center, which will give me access to
extensive resources and training to help me successfully transition to independence.

## Key facts

- **NIH application ID:** 10933497
- **Project number:** 5K08HG012374-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Joshua Ethan Motelow
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $254,727
- **Award type:** 5
- **Project period:** 2023-09-22 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10933497

## Citation

> US National Institutes of Health, RePORTER application 10933497, Genetic Risk Underlying Pediatric Critical Illness (5K08HG012374-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10933497. Licensed CC0.

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