Hormone Dependent Cancer

Nanopore technology to establish H4K12me1 as a novel biomarker in prostate cancer

Biological nanopore technology, a label-free, single-molecule sensing method, serves as a versatile platform for the precise detection and quantification of diverse analytes, including nucleic acids, proteins, and small chemical compounds. Our laboratory has recently identified KMT9 as a novel histone methyltransferase responsible for the monomethylation of histone H4 at lysine 12 (H4K12me1). KMT9 represents a promising therapeutic target for castration-resistant prostate cancer (CRPC), and we have developed potent KMT9 inhibitors (KMT9i) that effectively impair the proliferation of tumor cells, including castration and enzalutamide-resistant prostate cancer cells.

This project aims to precisely define H4K12me1 as a novel prognostic biomarker for KMT9 activity utilizing advanced nanopore technology. Specifically, we will apply this technology to quantitatively assess H4K12me1 levels both in vitro and within relevant prostate cancer cell lines. Subsequently, we will determine the modulation of H4K12me1 levels in KMT9-depleted cellular models and in cells treated with KMT9i. Furthermore, leveraging our established mouse prostate tumor model, we will investigate whether KMT9i treatment or KMT9 depletion induces measurable alterations in H4K12me1 levels within prostate tumor extracts and various biological fluids, including blood, urine, and extracellular vesicles. Ultimately, the developed nanopore assay will be adapted for high-throughput screening of novel KMT9 inhibitors.

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