Wet Laboratory

The Compbio Wizard Group’s wet laboratory, housed within the Systems Biology Department and led by Dr. Victor Mak, specializes in epigenomic profiling of FFPE samples to uncover the mechanisms of gene regulation in cancer.

In our recent study (Henikoff and Zheng et al., 2025, Science), we demonstrated that elevated RNAPII activity over genes and regulatory elements serves as a direct marker of hypertranscription in various human cancers. This approach enables precise mapping of genomic amplifications and selective sweeps in small clinical samples. Additionally, we found a significant correlation between high RNAPII levels at the 64 replication-coupled (RC) histone genes, which aligns with cytological evidence of elevated RNAPII activity during the S-phase in diverse organisms, including humans, mice, and Drosophila. These observations led us to hypothesize that hypertranscription’s primary role in cancer is to support the increased demand for histone production, facilitating rapid DNA packaging necessary for accelerated cancer cell proliferation.

We validated this hypothesis by conducting FFPE-CUTAC on a cohort of 30 human meningiomas. The results revealed that RNAPII activity at the 64 RC histone genes—representing only 1/100,000th of the human genome—effectively estimated WHO tumor grade and accurately predicted recurrence rates, corresponding to elevated proliferation gene expression. In contrast, predictions based on RNAPII levels at ribosomal protein genes or mitochondrial DNA abundance proved unreliable. Notably, elevated RNAPII activity at RC histone genes was also observed in invasive breast tumors, despite meningiomas being non-invasive. This discovery suggests that RNAPII FFPE-CUTAC at RC histone genes could provide a universal and cost-effective diagnostic tool for assessing cancer aggressiveness, potentially revolutionizing precision oncology.

Our lab integrates cutting-edge experimental techniques with advanced computational tools to bridge the gap between bench and bedside. From conducting wet lab experiments to developing novel computational models for data analysis, we are uniquely positioned to tackle complex challenges in cancer research.

We welcome collaborations across various cancer domains to drive innovation and improve patient treatment outcomes.