# Interrogating Protein Methyltransferases with Integrated Approaches

> **NIH NIH R35** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $790,240

## Abstract

Project Summary/Abstract: Protein methylation is an epigenetic event that is regulated by >60
human protein methyltransferases (PMTs). Because many PMT-associated methylation events are
invisible for conventional methods under designated cellular settings, our understanding of
epigenetic roles of PMTs is very limited. Selective perturbation of PMTs is of critical need towards
elucidating disease-specific roles of PMTs and formulating new therapy strategies. In the context of
these technology and knowledge gaps, in the past five years, our laboratory has focused on
developing novel technologies and implementing them to accurately annotate nonhistone
methylation events and downstream molecular mechanisms of PMTs. Meanwhile, our laboratory
has also devoted significant efforts to examine atomistic mechanisms underlying PMT-involved
catalysis and leverage them to rationally develop PMT inhibitors via distinct modes of interaction.
Here we plan to expand these findings. We envision characterizing nonhistone methylation events
associated with transcription activation with integrated approaches including chemical labeling and
Crisper/Cas9 editing. We will develop high-quality PMT inhibitors via SAM-competitive or covalent
modes, in particular with consideration of dynamic conformational landscapes of PMTs. The
completion of this proposal will unambiguously reveal molecular mechanisms of multiple PMTs in
relevant cellular contexts and deliver high-quality PMT inhibitors for perturbation. The additional
impact of our function-annotating and inhibitor-identifying strategies stems from their general
applicability to other methyltransferases.

## Key facts

- **NIH application ID:** 9937761
- **Project number:** 5R35GM131858-02
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Minkui Luo
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $790,240
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937761

## Citation

> US National Institutes of Health, RePORTER application 9937761, Interrogating Protein Methyltransferases with Integrated Approaches (5R35GM131858-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9937761. Licensed CC0.

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