# 3D Genome Mapping in the Human Brain and its Implications for Schizophrenia

> **NIH NIH F30** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $50,520

## Abstract

PROJECT SUMMARY
The human genome has traditionally been studied as a linear entity, ignoring how three-dimensional looping
interactions that bring together distal non-coding regulatory elements and proximal promoters may modulate
gene expression. Even with innovations in chromosome conformation capture techniques, the 3D
neuroepigenome remains largely underexplored. Exploration of cell-type-specific chromosomal conformations
will advance insight into hitherto unknown roles of non-coding sequences in the neurobiology of psychiatric
disorders such as schizophrenia. The basic mechanisms of these processes can be elucidated using a human
induced pluripotent stem cell-based platform, where isogenic neural cell types can be inexhaustibly derived
from one individual. In this proposal, we seek to explore how 3D chromatin interactions and topology change
based on cell type given an identical genotypic background in normal human neural differentiation, from neural
progenitor to either astrocyte or excitatory neuron. I hypothesize that identity-specific regulatory element-
promoter loops will emerge that connect noncoding sequences to transcription start sites, thereby modulating
gene expression. By overlaying known schizophrenia “risk loci,” many of which are in noncoding regions, on
neuron-specific chromatin loops, I will attempt to find those loci that occur in sequences of the genome critical
for loop formation. Finally, I hypothesize that by manipulating such candidate (i.e., risk-loci-bearing) loops with
targeted CRISPR epigenetic editing, I will observe changes in gene expression. Findings from the proposed
project will greatly advance knowledge in the field of how the 3D genome can quite literally contribute to the
risk architecture of psychiatric disease, promoting the development of more effective diagnosis and treatment
in the future.

## Key facts

- **NIH application ID:** 9898467
- **Project number:** 5F30MH113330-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Prashanth Rajarajan
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2017-04-05 → 2021-04-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898467

## Citation

> US National Institutes of Health, RePORTER application 9898467, 3D Genome Mapping in the Human Brain and its Implications for Schizophrenia (5F30MH113330-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9898467. Licensed CC0.

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