# Comprehensive mapping of multimodal chromatin state in single cells

> **NIH NIH K99** · NEW YORK GENOME CENTER · 2021 · $115,628

## Abstract

PROJECT SUMMARY
Many non-Mendelian (polygenic) human genetic diseases involve multiple causal loci in noncoding regions of
the genome, implicating mutations in regulatory elements rather than protein-coding genes as the cause of these
diseases. Deciphering the etiology of these human genetic diseases requires an understanding of how genes
are regulated during development and homeostasis to produce functional cell states. This regulation is encoded
both through epigenetic chromatin state, and genetically encoded in the DNA sequence of regulatory elements
such as enhancers, promoters, silencers, and insulators. However, these regulatory elements and their activity
states in human cells are not resolvable with current technologies. As aberrant gene regulation likely underlies
many human diseases, understanding (1) the function of regulatory DNA elements and (2) their activity dynamics
during healthy human development are essential. To address these two problems, I propose to: (i) develop new
experimental methods to profile multimodal chromatin state in single cells; (ii) identify alterations in regulatory
element activation states that guide cell fate choice during human hematopoiesis; (iii) identify the DNA sequence
features important for regulatory element function; (iv) build community tools and resources for the analysis of
single-cell chromatin data. Together these aims will provide methods and resources for the interrogation of the
human functional genome, and the identification of regulatory state dynamics that generate human cell types.
To succeed in achieving these aims, I will pursue additional training supported by co-mentors Dr. Rahul Satija
(single-cell biology), Dr. Vijay Sankaran (hematopoiesis), Dr. Danny Reinberg (gene regulation), and Dr. David
Knowles (machine learning). I have developed a 5-year career development plan that integrates scientific training
in hematopoiesis and gene regulation, practical training and mentorship in deep learning, extensive leadership
training through courses and mentorship, and seminars and workshops on academic writing. My team of
scientific mentors will provide further guidance and mentorship in academic job searches. The New York
Genome Center is an ideal environment for research and further career development, providing the cutting-edge
research facilities and opportunities for further career development in a rich interdisciplinary environment.
Completion of the proposed research program and career development plan will launch my independent
scientific career as a leader in the field of single-cell epigenomics.

## Key facts

- **NIH application ID:** 10106155
- **Project number:** 1K99HG011489-01
- **Recipient organization:** NEW YORK GENOME CENTER
- **Principal Investigator:** Tim Stuart
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $115,628
- **Award type:** 1
- **Project period:** 2021-01-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10106155

## Citation

> US National Institutes of Health, RePORTER application 10106155, Comprehensive mapping of multimodal chromatin state in single cells (1K99HG011489-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10106155. Licensed CC0.

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