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RESEARCH

Research projects in the Woelk lab:

Biomarker development.

 

We are applying methodology from the field of oncology to the development of biomarkers for HIV pathogenesis and mental illness. Specifically we are analyzing gene expression in patient samples using microarrays capable of probing the whole genome. Patient samples have been divided into one of two classes, i.e. control vs. disease (healthy vs. schizophrenia) or before drug and after drug (Drug naive HIV patients vs. HAART treated HIV patients). Then we use class prediction methods to identify the subset of genes that can be used to predict the class of a blinded sample. In this way we are developing diagnostic biomarkers for schizophrenia and HIV pathogenesis.


Identification of interferon stimulated genes.

 

Interferon (IFN) was first discovered over 50 years ago and shown to have anti-viral properties.  To this day, the full repertoire of genes that are induced by IFN, and the extent to which this induction varies between cell types and different classes of IFN, remain unknown.  Using whole genome microarrays our lab is currently trying to unravel the genes that are induced by Type I, II and III interferons. 

 

Investigation of host factors that inhibit HIV replication.

 

Our lab has shown that HIV infection of macrophages results in the induction of the interferon response and interferon stimulated genes (ISGs) [Woelk et al. 2004].  However, this interferon mediated antiviral response is ultimately unable to protect the human host from HIV infection.  In contrast, macrophages treated with interferon prior to HIV infection are protected from virus replication.  Our lab is currently investigating the nature of this protection to identify ISGs with anti-HIV properties.

 

Molecular evolution of cytokines.

 

Cytokines are integral to cell signaling and are at the forefront of the innate immune response.  Therefore pathogens often evolve to outmaneuver cytokine signaling, for example, by encoding receptor homologs to soak up the cytokine. In response, the host must evolve to escape this pathogen interference.  This evolutionary "arms race" make cytokines interesting targets for  analysis and our lab characterizes these molecules for selection pressure, and gene conversion and duplication [Woelk et al. 2007].

 

Pathogen vaccine design using reverse vaccinology.

 

Reverse Vaccinology (RV) facilitates rapid and cost-effective vaccine design through the use of bioinformatics to identify putative protective antigens in pathogen proteomes that can then be formulated into subunit vaccines.  This approach has been used by others to develop a vaccine against serogroup B Meningococcus that is now in Phase I clinical trials.  RV has important implications for public health since it can accelerate vaccine design for any pathogen for which the complete genome sequence, and hence proteome, is available.  Our lab is currently developing software to combine all the bioinformatic tools required for RV analysis into a single package.

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