Research group Epigenetics

The research group epigenetics focuses on the mechanisms that regulate human genome behaviour. These mechanisms are primarily responsible for generating cell-type specific gene expression profiles, which give rise to the large variety of cellular identities with diverse functionalities in the human body. Changes in epigenetic regulation are often at the core of pathological processes that lead to cellular dysfunctionality and result in organ malfunction and disease.

  • Principle Investigator
    • Research Department Antiviral Strategies (Prof Joachim Hauber), Heinrich Pette Institut (HPI), Leibniz Institute for Experimental Virology, Hamburg
    • EPILOG (www.epilog-infect.org), joint research initiative University Medical Center Hamburg-Eppendorf (UKE), University of Hamburg (UHH) and Heinrich Pette Institute (HPI)
    • German Center for Infection Research (DZIF)
    • Medical Faculty, University of Hamburg
    • UKE Clinician Scientist Programme
    • GILEAD Förderprogramm Infektiologie

Research projects

Crosstalk of proviral DNA with the human genome in chronic infection with human immunodeficiency virus (HIV)

Forschung DNA-Labor

A variety of human pathogenic viruses can enter a state of viral latency upon infection. This dormant state is thought to enable evasion from immune surveillance, permits long term persistence of the viral genome within the host cell and establishment of a chronic infection.

HIV replicates through integration of proviral DNA into the genome of infected cells. This viral life cycle has several intriguing features. Integrated proviral sequences can be transcriptionally repressed, resulting in a latently infected reservoir that is hampering current efforts to eradicate HIV once infection has occurred. Furthermore, chronically HIV-infected patients accumulate a large number of defective proviral sequences within the genomes of HIV target cells. Very little is known to date about the impact of these sequences on host cell biology.

The research project focuses on the mechanisms that govern choice of HIV integration site as well as HIV latency establishment and maintenance. Particular emphasis is put on epigenetic regulatory mechanisms. Generally we would like to understand how HIV proviral DNA integration impacts on host cell physiology.

In order to approach these questions, we employ a range of molecular biology techniques, focusing in particular on the analysis of local and genome-wide epigenetic and translational changes. We make use of site-specific targeting technologies (e.g. genome editing) in order to generate suitable cellular model systems.

Overall, we expect that our studies will promote our understanding of the biology of HIV infection and in particular of the impact of chronic infection on human host physiology. Eventually this understanding will be essential to optimize therapeutic strategies.

  • Team members
  • Team members

    Team members

    Dr. med. Ulrike Lange, PhD (Projektleitung)

    Dr. rer. nat. Julia Bialek

    Daan Baeten (BSc)

  • Lange UC, Bialek JK, Walther T, Hauber J. Pinpointing recurrent proviral integration sites in new models for latent HIV-1 infection. Virus Research. 2018, Mar 14; 249:69-75

    Bialek JK, Dunay GA, Voges M, Schäfer C, Spohn M, Stucka R, Hauber J, Lange UC. Targeted HIV-1 Latency Reversal Using CRISPR/Cas9-Derived Transcriptional Activator Systems. PLoS One. 2016, Jun 24;11(6):e0158294.

    Karpinski J, Hauber I, Chemnitz J, Schäfer C, Paszkowski-Rogacz M, Chakraborty D, Beschorner N, Hofmann-Sieber H, Lange UC, Grundhoff A, Hackmann A, Schrock E, Abi-Ghanem J, Pisabarro MT, Surendranath V, Schambach A, Lindner C, van Lunzen J, Hauber J, Buchholz F. Directed evolution of a recombinase that excises the provirus of most HIV-1 primary isolates with high specificity. Nat Biotech. 2016, Apr;34(4):401-9.