# Mechanism and Inhibition of Histone Modifications

> **NIH NIH R35** · UNIVERSITY OF GEORGIA · 2024 · $372,972

## Abstract

Protein methylation on arginine and lysine residues represents a type of versatile posttranslational modifications
occurring in all eukaryotic organisms. Protein methyltransferases regulate a plethora of cellular processes
ranged from gene transcription, RNA splicing, translation, metabolic pathways, to signal transduction. Many
protein methyltransferases are found to be overexpressed or mutated in common human diseases such as
cancer, inflammation, diabetes, neurological disorders, and infection. Hence, protein methyltransferases are
highly promising novel molecular targets in drug discovery. However, biological functions of the majority of
protein methyltransferase enzymes in dictating normal physiology and disease pathways are only poorly defined.
Our long-term research goal is to elucidate biological pathways whereby key protein methyltransferases
contribute to the pathogenesis of recalcitrant diseases such as cancer and infection, and meanwhile to discover
new structural chemotypes for protein methyltransferase-targeted therapy. The present research program is
aimed at investigating molecular mechanisms and functions of protein methylation catalyzed by key
methyltransferases. Our effort is coupled with and aided by development and application of innovative chemical
biology methods and tools. Built upon our recent preliminary results, we will implement experiments to elucidate
novel molecular mechanisms and regulation of protein arginine methyltransferase (PRMT) activities. We will
extend our efforts to investigate the activity, structure and function of untapped protein methyltransferases,
including those in different organisms such as infectious pathogens. Particular efforts will be directed to develop
isoform-selective modulators and probes for important PRMT members and apply them to elucidate PRMT-
regulated cellular pathways and disease processes. Further efforts will be invested to interrogate potential cross-
interactions of protein methylation with lysine acetylation in orchestrating biological regulation. The results of the
proposed research together will yield an in-depth understanding of the regulatory mechanism and biological
significance of protein methylation in the control of normal physiology and disease pathology, and translate
laboratory research leads into therapeutic candidates for the treatment of protein methyltransferase-controlled
ailments.

## Key facts

- **NIH application ID:** 10813018
- **Project number:** 5R35GM149230-02
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Y. George Zheng
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $372,972
- **Award type:** 5
- **Project period:** 2023-04-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813018

## Citation

> US National Institutes of Health, RePORTER application 10813018, Mechanism and Inhibition of Histone Modifications (5R35GM149230-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10813018. Licensed CC0.

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