# Molecular Imaging Agents for Monitoring Lysine Demethylases in Cell

> **NIH NIH R35** · EMORY UNIVERSITY · 2020 · $382,560

## Abstract

PROJECT SUMMARY
Protein lysine methylation is a reversible process controlled by lysine methyltransferases (KMTs or methyl
writers) and lysine demethylases (KDMs or methyl erasers) in human cells. Most studies on these KMTs and
KDMs have focused mainly on their functions inside the nucleus. More than half of these KMTs and KDMs,
which are present in the nucleus are also localized in the cytoplasm but very little is known about their
functions in this subcellular compartment. The abnormalities in these enzymes are directly associated with
cancers, inflammation and other diseases. Despite the critical importance of the KDMs in different subcellular
compartments, there is a substantial gap between their global analysis and effective methods available to
achieve it. The long-term goal of this research program is to develop a mechanistic understanding of how
“lysine methylome” is maintained at a subcellular level and how these chemical markers modulate cell
signaling. The current focus is to develop a new class of chemical tools that report on KDM activities in living
cells at a subcellular level. This new family of chemical tools will be deployed to determine the activity of KDMs
in different subcellular compartments, and their regulation by substrates, and local cofactors. The primary
biological interests right now deal with roles of KDMs outside of the nucleus, in particular, the cytoplasm and
mitochondria, while pursuing mechanistic studies in the context of cancer. The proposed research contains
four innovations to decode the intracellular KDM activities with subcellular resolution. First, is the development
of new small molecule probes with unique chemoselectivity towards lysine, and high stability towards
hydrolysis, which is ideal for studying KDMs in cells. Second, is the development of molecular imaging agents
to monitor the activity of KDMs and how they are regulated inside the cells. Third, is to determine the activity of
the specific KDMs by incorporating recognition elements on the probe. Fourth, is the development of organelle
selective molecular imaging agents to study the role of KDMs in different subcellular compartments and their
subcellular localization, which is currently impossible to determine with existing techniques. These probes are
capable of determining KDM activities and their role in various diseased states thus of immense therapeutic
interest. This research will have extensive applications in biomedical field by providing a better understanding
of KDMs functions in different subcellular compartments, the molecular mechanisms of diseases, thus assist in
the discovery of novel protein biomarkers, and combination-therapy for the treatment of cancer.

## Key facts

- **NIH application ID:** 10214799
- **Project number:** 7R35GM133719-03
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Monika Raj
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,560
- **Award type:** 7
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214799

## Citation

> US National Institutes of Health, RePORTER application 10214799, Molecular Imaging Agents for Monitoring Lysine Demethylases in Cell (7R35GM133719-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10214799. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*