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Ragon Institute Fellows Recieve 2011 MGH ECOR Award
November 22, 2011

Srinka Ranasinghe, PhD and Filippos Porichis, PhD were awarded the MGH Executive Committee on Research (ECOR) Fund for Medical Discovery. They were two of 22 applicants selected from a pool of 124 applications from the MGH research community for doing challenging and inspiring work in their field.

Both awardees recognize that the award will act as an important stepping stone in their careers.

"As a young scientist with no independent funding, this award gives me the opportunity to generate strong preliminary data that will provide me with a solid background and a basis for future projects. These projects will enable me to apply for my own funding, with the goal of building an independent research group." said Dr. Porichis.

	Srinka Ranasinghe, PhD Project Title: Harnessing HIV-specific CD4 T cell responses
Project Background: Currently, a major challenge to the development of an effective T-cell based vaccine is the vast array of HLA molecules that present antigenic peptides to T cells. To overcome this obstacle, it will be essential to define the HLA restriction of HIV-specific T-cell responses and identify epitopes that can bind to many different HLA alleles to effectively cover a large proportion of genetically diverse populations. Yet, the specificity and HLA class II restriction of CD4 T cell responses in HIV infection has not been assessed. Indeed, of the ~350 peptides currently listed as CD4 T cell epitopes in the Los Alamos HIV Immunology database, precise HLA class II restriction has only been determined for <5% of epitopes. Thus our project aims to conduct a comprehensive study to define the specificity and HLA class II restriction of these HIV-specific CD4 T cell responses and to importantly identify ‘promiscuous’ epitopes that are presented in the context of multiple HLA class II molecules.
	Filippos Porichis, PhD Project Title: Impact of BATF on HIV-specific CD4 T cell dysregulation and viral replication
Project Background: The inexistence of an effective vaccine and the failure of antiretroviral (ART) therapy to clear the pathogen and restore antiviral immune function are major barriers for the eradication of HIV infection. Identifying the mechanisms that mediate T cell dysfunction will provide crucial information for future vaccine design as well as novel targets for therapeutic interventions in order to improve current treatment strategies. A research focus of our group is to uncover the intracellular pathways that govern HIV-specific CD4 T cell dysfunction. The goal of my project “Impact of BATF on HIV-specific CD4 T cell dysregulation and viral replication” is to understand the role of played by a transcription factor called Basic leucine zipper transcription factor, ATF-like, or BATF. This molecule, known to be important for differentiation of some T cell subsets, was recently shown to regulate HIV-specific CD8 T cell dysfunction. In this project, I will investigate the role that BATF plays in HIV-specific CD4 T cells. I will also define how BATF modulates viral replication in target cells. Transcription factors, such as BATF, are promising targets for therapeutic interventions since they coordinate expression of gene patterns and decide differentiation, functions and fate of T cells.

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