# Unraveling mechanisms of genome regulation to understand and improve human health

> **NIH NIH R35** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2021 · $410,000

## Abstract

Summary
The human body is constructed during through tightly orchestrated patterns of gene expression
during embryonic and postnatal development. Perturbations in gene regulation during
development are thought to be a major substrate for natural selection and have likely contributed
to the evolution of the human form. The molecular processes that contributed to sculpting human
specific features of our limbs and brains, can have deleterious consequences when a critical gene
or regulatory sequence is affected. Defective gene regulation during embryonic development can
result in a variety of structural and functional defects such as congenital heart defects, orofacial
clefting, or neurological dysfunction. In cases where a birth defect is not readily observed the
individual may be instead be predisposed to various diseases later in life including diabetes or
cancer. While our understanding of the genetic code for protein coding genes allows us to make
predictions about disease risk our limited understanding of the information encoded in the rest of
our genome prevents such predictions and causative assignments. Over the past several years
functional annotations of the genome in tissue and developmental stage specific contexts have
revealed over half a million potential regulatory elements. We and others have shown that
variants linked to diseases and phenotypes of particular tissues are enriched in regulatory
sequences that are active in those tissues or during their development. This has been particularly
fruitful for defects related to craniofacial and heart development. The work proposed aims to build
on these annotations to identify the genes that are controlled by these tissue-specific regulatory
sequences and the consequences of variation in those sequences. Using culture and organoid
models of early human cardiac development we aim to dissect the regulatory architecture that
build the heart and malfunctions in congenital heart defects.

## Key facts

- **NIH application ID:** 10167386
- **Project number:** 2R35GM119465-06
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Justin Lee Cotney
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $410,000
- **Award type:** 2
- **Project period:** 2016-09-09 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167386

## Citation

> US National Institutes of Health, RePORTER application 10167386, Unraveling mechanisms of genome regulation to understand and improve human health (2R35GM119465-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10167386. Licensed CC0.

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