Isaac Hilton specializes in engineering the human genome, epigenome, and transcriptome. He develops CRISPR/Cas9-based technologies and other synthetic biology tools to mechanistically define and control the relationships between epigenetic modifications, gene expression, and cellular processes.
Due to the human epigenome’s overarching ability to organize DNA and direct which genes are turned on or off, epigenome engineering holds tremendous potential to overcome longstanding challenges facing basic research. In addition, this emerging technology is revolutionizing the ability to precisely manipulate gene expression patterns that impact the balance between human health and disease.
New research in the Hilton laboratory, which is supported by a $2 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT), includes deciphering how oncogenes like MYC and MYB drive the onset of multiple human cancers and how different physiological levels of these genes globally alter cellular chromatin structure, transcriptional programs, and phenotypes. In concert with these efforts, Hilton’s research group uses cutting-edge approaches to model the multistep genomic disruptions associated with human cancer types that resist treatment.
The Hilton laboratory collaborates with physicians and researchers in the Texas Medical Center and elsewhere to translate mechanistic biological insights into innovative ways to personalize treatments for disease.
Prior to joining Rice in 2018, Hilton gained expertise in engineering the human genome and epigenome with programmable CRISPR/Cas9-based nucleases, transcriptional factors, and chromatin remodelers. As a postdoctoral fellow working with Professor Charles Gersbach at the Department of Biomedical Engineering and Center for Genomic and Computational Biology at Duke University, Hilton used dCas9 as a platform to deliver different enzymatic effector domains and thereby control gene regulation and chromatin structure at specified genomic locations.
Hilton earned his Ph.D. from the University of North Carolina at Chapel Hill, where he worked with Professor Dirk Dittmer in the Lineberger Comprehensive Cancer Center and the Department of Microbiology. His work centered on establishing how transcriptional circuits and epigenetic-regulatory mechanisms control the life cycle and pathology of a human tumor virus that causes sarcomas and B-cell lymphomas.
Hilton is an inventor on several patents and journal publications related to genome, epigenome, and cellular engineering technologies.
Appropriately coordinated gene expression programs drive all cellular functions. Pioneering biomedical research spanning several decades has clarified many of the mechanisms governing human gene expression, nevertheless, a comprehensive understanding of how genes are regulated remains both lacking and critically needed. Recent advances in genome engineering, synthetic biology, and functional genomics are enabling new ways to manipulate and understand cellular transcription and epigenetic modifications. The Hilton lab is focused upon innovatively combining these advances to decipher, and ultimately engineer, gene-regulatory mechanisms. Our work is aimed at understanding the fundamental principles of human gene regulation and repurposing these principles to improve the ability to control cellular behaviors and combat human diseases.
The Hilton laboratory employs functional genomics, genome and epigenome engineering, and other synthetic biology technologies to achieve its research goals. Efforts span three interrelated areas: i) decoding basic mechanisms governing gene regulation in human health and disease; ii) engineering gene expression programs to predictably control human cells and; iii) developing new biomolecules to manipulate epigenetic marks and transcriptional networks