Isaac Hilton specializes in engineering the human genome and epigenome. 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 epigenomeâ€™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 genes 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, Hiltonâ€™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 at the University of Texas MD Anderson Cancer Center and elsewhere to translate mechanistic biological insights into innovative ways to personalize clinical oncology.
Prior to joining Rice, 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 Center for Genomic and Computational Biology and the Department of Biomedical Engineering 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.
The work of Hilton and colleagues has provided direct evidence that the acetylation of chromatin is causally linked to gene activation, and has expanded the ability to synthetically control transcription from regulatory regions of the human genome.
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 tumor virus that causes human sarcomas and B-cell lymphomas.
Hilton is an inventor on pending and approved patents related to genome and epigenome engineering technologies. His graduate and postdoctoral research have resulted in 10 journal publications.
Appropriately coordinated gene expression programs are central to all cellular functions. Pioneering biomedical research spanning several decades has clarified many of the mechanisms governing human gene expression. Despite this tremendous progress, a comprehensive understanding of how genes are regulated remains both lacking and critically needed. Recent advances in synthetic biology and genome engineering are enabling new ways to manipulate cellular transcription and epigenetic modifications. The Hilton research group is focused upon transforming these cutting-edge synthetic tools into innovative ways 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:
Klann, T.K., Black, J.B., Chellappan, M., Safi, A., Song, L., Hilton, I.B., Crawford, G.E, Reddy, T.E., and Gersbach, C.A., CRISPR-Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome.Â Nature Biotechnology (2017).
Thakore, P.I., Black, J.B., Hilton, I.B., and Gersbach, C.A., Editing the epigenome: technologies for programmable transcription and epigenetic modulation. Nature Methods (2016).
Hilton, I.B., and Gersbach, C.A., Enabling functional genomics with genome engineering. Genome Research (2015).
Hilton, I.B., Dâ€™Ippolito, A.M., Vockley, C.M., Thakore, P.I., Crawford, G.E., Reddy, T.E., and Gersbach, C.A., Epigenome editing by a CRISPR/Cas9-based acetyltransferase activates genes from promoters and enhancers. Nature Biotechnology (2015).
Kabadi, A.M.*, Ousterout, D.G.*, Hilton, I.B., and Gersbach, C.A., Multiplex CRISPR/Cas9-based genome engineering from a single lentiviral vector. Nucleic Acids Research (2014). *Equal Contribution
Hilton, I.B., Simon, J.M., Lieb, J.D., Davis J.I., Damania, B., and Dittmer, D.P., The open chromatin landscape of Kaposiâ€™s sarcoma-associated herpesvirus. Journal of Virology (2013)
Roy, D., Sin, S.H., Lucas, A., Venkataramanan, R., Wang, L., Eason A., Veenadhari, C., Hilton, I.B., Damania, B., and Dittmer, D.P., mTOR inhibitors block Kaposi sarcoma growth by inhibiting essential autocrine growth factors and tumor angiogenesis. Cancer Research (2013)
Hilton, I.B., and Dittmer, D.P., Quantitative analysis of the bidirectional viral G-protein-coupled receptor and lytic latency-associated nuclear antigen promoter of Kaposi's sarcoma-associated herpesvirus. Journal of Virology (2012)