# Mapping Integrated Single-Cell Chromatin Accessibility with the Single-Cell Transcriptional Landscape in Pediatric Type 2 Diabetes

> **NIH NIH K01** · EMORY UNIVERSITY · 2024 · $151,902

## Abstract

ABSTRACT
A time-sensitive window of opportunity exists in preventing and treating type 2 diabetes (T2D) in youth where
the identification of new molecular targets could be used for disease prevention and control. The key objectives
of this proposal are twofold. First, this proposal provides a combined strategy of didactic training and mentored
training for (a) the measurement of single-cell chromatin accessibility and single-cell transcription factors
associated with T2D using innovative wet-lab techniques; (b) bioinformatics, including machine learning, for the
integration of multi-omic, clinical, and sociodemographic data to classify phenotypes of T2D; and (c) leadership
and management skills required of high-quality clinical studies. The co-mentors will provide integrated training
in single-cell epigenomic and transcriptomic lab techniques, data analyses, and coordinated training with four
advisory committee experts. The second key objective of this proposal is the implementation of hypothesis-
driven research aims around subtypes of immune cells that have pro-inflammatory vs. anti-inflammatory
function. Single-cell sequencing will overcome the limitations of bulk epigenetic and RNA studies and improve
attribution of gene regulation in individual cell types. We leverage the recruitment platform from our KL2 parent
study to recruit youth and examine single-cell chromatin accessibility associated with T2D. In this cross
sectional study, we will collect new peripheral blood samples from two groups of youth aged 10-20-years: new-
onset T2D case participants (n=96,000 cells from 24 participants) and healthy, normoglycemia control
participants (n=96,000 cells from 24 participants), obtained during a single study visit by oral glucose tolerance
test. Our specific aims include (a) testing the hypothesis that T helper (Th)-17 cells will be more abundant in
T2D compared to healthy control participants and regulatory T cells (Treg) more abundant in control
participants, (b) testing the hypothesis that genes determining T Helper cell type, Rorc and Foxp3, will have
different levels of chromatin accessibility and different gene expression in clinical groups, and (c) machine
learning based on high-throughput single-cell epigenomic, transcriptomic, sociodemographic, and clinical data
to classify phenotypes of T2D. In summary, this proposal assembles a team of mentors and advisors across
scientific disciplines to provide thorough training in research related to single-cell epigenetics, gene expression,
bioinformatics, machine learning, and leadership in clinical studies, with emphasis on the development of
future research for NIH grant support. The innovations of the proposed analyses, namely the integration of
single cell epigenetic and single cell gene expression, will enable construction of gene regulatory networks that
may inform new strategies to protect youth from T2D and related complications.

## Key facts

- **NIH application ID:** 10829945
- **Project number:** 5K01DK133669-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Lisa Rachel Staimez
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $151,902
- **Award type:** 5
- **Project period:** 2023-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10829945

## Citation

> US National Institutes of Health, RePORTER application 10829945, Mapping Integrated Single-Cell Chromatin Accessibility with the Single-Cell Transcriptional Landscape in Pediatric Type 2 Diabetes (5K01DK133669-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10829945. Licensed CC0.

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