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Ruobing Wang, M.D., Ph.D.

		Associate Member, Seattle Biomedical Research Institute Email: ruobing.wang@sbri.org Organism under study: Malaria

Mission
Dr. Wang is combining her expertise in immunology and clinical trial experience with that of other scientists in the Malaria Antigen Discovery (MAD) Program to discover new vaccines or drugs for malaria.

Research
For more than 10 years, Dr. Wang has been involved in the design, production and testing of vaccines against malaria parasites. She has extensive knowledge of T cell immunology and the methods for the induction and characterization of T cell responses in mice, non-human primates and humans. Dr. Wang has worked on the development of a high-throughput immunological approach to rapidly characterize potential vaccine candidates identified through the determination of the malaria parasite genome sequence.

Her areas of research include:

Development of a high throughput in vitro platform to identify novel antigens: Genome sequences for most of the important pathogens of humans or animals have been completed. The challenge for vaccine developers has been to develop “high throughput” methods for antigen discovery that can capitalize on the flood of information being generated by genomic approaches. Dr. Wang has developed an in vitro platform for the identification of novel antigens that are targets of T cell responses in humans using P. vivax as a model. Besides applying this method to Plasmodium (see below), Dr. Wang would like to develop antigen identification programs for other infectious agents.

Identification of preerythocytic stage antigens of Plasmodium vivax by characterizing the immune responses in naturally-exposed Duffy negative humans. Malaria vaccines targeting the pre-erythrocytic stages of the parasites are considered ideal (see research done by SBRI’s Stefan Kappe, Ph.D.), as they would block parasite entry to the liver or its further development in the hepatocyte and thereby blood stage infections. Using the P. vivax genome sequence information and genetic differences in the susceptibility of humans to blood stage P. vivax infectious, Dr. Wang, along with collaborators in Columbia, have identified potential P. vivax liver stage antigens (See Wang, et al. Eur J Immunol 2005).

Use of human DNA microarrays to define the minimum set of immunological markers whose expression can be used to predict the outcome of the host immunity to P. vivax or P. falciparum infections, vaccination or therapeutic interventions. A difficult challenge facing immunologists is to learn which immunological responses provide protective immunity and to identify the signatures of protective immune responses in humans. Dr. Wang is using DNA microarray technology to study the differential gene expression profiles in immune cells from humans naturally exposed to P. vivax malaria infections after stimulation with P. vivax-specific antigens. Identification of co-regulated genes will shed light on the mechanisms involved in T cell activation (effector function and maintenance (memory) in responses to infections and candidate vaccines and could be used to predict the outcome of vaccine trials.

Themes
     *  Design, production and testing of malaria vaccines
     *  Identification of novel antigens
     *  Pre-erythrocytic stages of malaria parasites

Laboratory Accomplishments
     *  Demonstrated that vaccination with a multi-component P. falciparum DNA vaccine could simultaneously induce multiple antigen-specific responses in non-human primates, which led to the first malaria DNA vaccine trial in humans.
     *  Showed, for the first time in normal, healthy humans, that a DNA vaccine elicited killer T lymphocytes.
     *  Developed an in vitro screening platform to identify novel proteins that are targets of cell-mediated immunity in humans, predicted via genome sequences.

Dr. Wang's research is currently supported by funding from NIAID and SBRI.

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