Isabelle Derre

Derre, Isabelle

Primary Appointment

Assistant Professor, Microbiology, Immunology, and Cancer Biology


  • Postdoc, Host/Pathogen Interaction, Tufts University School of Medicine
  • PhD, Microbiology, Pasteur Institute

Contact Information

Jordan Hall, 7th floor, Room 7212
P.O. Box 800734
Charlottesville, VA 22908
Telephone: 434.924.2330
Fax: 434.982.1071

Research Disciplines

Genetics, Infectious Diseases/Biodefense, Molecular Biology

Research Interests

Host/pathogen Interaction - Chlamydia Infection

Research Description

We study the molecular mechanisms underlying the interaction between pathogens and their mammalian host. In particular, we investigate how the obligate intracellular bacteria Chlamydia trachomatis has evolved to manipulate the eukaryotic cell and establish an intracellular niche favorable for survival and replication.

Why study Chlamydia trachomatis pathogenesis?
Chlamydia trachomatis is a gram-negative bacterial pathogen of tremendous public health concern. Ocular serovars lead to trachoma and genital serovars are the leading cause of bacterial sexually transmitted disease in developed countries. Despite the implementation of C. trachomatis screening programs, and the effectiveness of antibiotics to treat trachoma and uncomplicated sexually transmitted chlamydial infection, case rates are not declining and reinfection rates are increasing.

Our general approach and major findings:
Chlamydia are characterized by a biphasic developmental cycle that occurs exclusively in the host cell. Once internalized, Chlamydia reside in a membrane bound compartment, named the inclusion and alternate between an infectious form (Elementary Body, EB) and a replicative form (Reticulate Body, RB). The cycle lasts two to three days depending upon the species. If our knowledge of the cellular processes that are targeted by Chlamydia has greatly increased over the past 10 years, we have only begun to identify the bacterial and host factors required for bacterial development.
In the past, genetic intractability of Chlamydia has made it challenging to fully dissect the role of virulence factors involved in pathogenesis, but tremendous advances have recently occurred and genetic tools (transformation, mutagenesis) are emerging. We have contributed through the development of cloning vectors and a conditional gene expression system.
We have also contributed to the field through the identification of host factors involved in Chlamydia infection using the RNAi methodology. One of our candidates led us to uncover that, in addition to vesicular trafficking, C. trachomatis hijacks the non-vesicular lipid transfer machinery at zone of close apposition (10-50 nm) between the ER and the inclusion membrane. These specialized platforms are referred to as ER-Inclusion membrane contact sites (MCSs). We have shown that the C. trachomatis type III effector protein IncD, the host lipid transfer protein CERT and the ER resident protein VAPB interact at ER-Inclusion MCSs. In addition, we have recently shown that the ER calcium sensor STIM1 co-localizes with CERT and VAPB at C. trachomatis inclusion and therefore represents a novel component of ER-Inclusion MCSs.

Our current research:
Our goal is to further characterize the structure and function of ER-Inclusion MCSs during C. trachomatis infection. Our hypothesis is that specific C. trachomatis and host factors localize to ER-Inclusion MCSs and create a specialized microenvironment that mediate the bacterial acquisition of essential nutrients, such as lipids. Our approach combine cell biology, molecular biology, microbiology and confocal microscopy techniques together with the newly developed genetic tools for Chlamydia. It will lead to the identification and characterization of both bacterial and host factors that localize to MCSs and therefore help us better understand the function of ER-Inclusion MCSs at the molecular level. This will further our understanding of the molecular mechanisms involved in the infection process and may reveal drug targets to facilitate the translational research development of tools to prevent, treat and control Chlamydia infection.

Selected Publications