# Super-resolution microscopy for dynamic analysis of focal enhancer amplifications in cancer

> **NIH NIH R33** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $379,981

## Abstract

Project Summary
 Cancer is often thought of as a genetic disease. For example, specific protein-coding mutations can
activate cancer-causing oncogenes. However, cancer-causing oncogene can also be activated by alterations to
non-coding DNA. Specifically, enhancers are non-coding DNA elements that can activate gene expression
across vast genomic distances. In numerous cancers, genetic alterations cause enhancers to over-activate
cancer-causing oncogenes. This is also referred to as enhancer hijacking.
 Here we focus on epithelial cancers, where enhancers that activate the MYC oncogene get duplicated
and focally amplified. This correlates with higher MYC expression and increased tumorigenicity. But the
molecular mechanisms are not well understood. Achieving a mechanistic understanding is important since it may
identify molecular ‘Achilles Heels’ that can be targeted therapeutically.
 Achieving an understanding of the mechanism of enhancer action in general and enhancer hijacking in
cancer in general requires an ability to measure at high spatiotemporal precision enhancer-gene communication
in living cells. The proposed project will establish and validate such a platform based on super-resolution
microscopy, which make it possible to track individual enhancers and genes with a precision of ten nanometers
in living cells as well as gene activity in real time. Significant efforts will be devoted to validating the super-
resolution microscopy approach through extensive control experiments. Significant efforts will also be devoted
to disseminating the technological innovations and know-how to the greater community.
 In summary, we propose to establish and validate an innovative and integrative experimental and
computational super-resolution microscopy platform for studying focal enhancer amplifications. While our initial
focus is on amplifications of MYC enhancers in epithelial cancers, the proposed platform is likely to find
widespread use beyond MYC.

## Key facts

- **NIH application ID:** 10170545
- **Project number:** 1R33CA257878-01
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Anders Sejr Hansen
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $379,981
- **Award type:** 1
- **Project period:** 2021-04-05 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10170545

## Citation

> US National Institutes of Health, RePORTER application 10170545, Super-resolution microscopy for dynamic analysis of focal enhancer amplifications in cancer (1R33CA257878-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10170545. Licensed CC0.

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