Academic Background

Ph. D. (1974) University of Pennsylvania

Regulation of B Cell Survival Control of Virus Expression by Lymphocyte Activators

Our laboratory is determining the soluble and cell associated ligands that maintain virgin B lymphocytes in the long-lived lumphocyte pool. In particular, we are interested in the transcriptional and post translational regulation of pro-apoptotic and anti-apoptotic proteins that control B cell homeostasis and B cell survival during stress. For these experiments we are comparing B cells from normal mice to those from mice with an X-chromosome linked immunodeficiency, as this mutation significantly reduces peripheral B cell survival. Other studies in the laboratory focus on the mechanism by which a virus infection is controlled in lymphocytes by lymphocyte activators. We have shown that virus transcription, protein translation, assembly and release of infectious particles are all processes regulated by lymphocyte activators acting on resting infected cells. We are using these observations to develope new modalities to control both acute and chronic virus infections.

Rotation Projects

1. Aged mice have severely diminished numbers of naïve B cells and mount poor responses to "new antigens" despite the fact that B cell lymphogenesis continues for the life of the animal. We hypothesize this may be due to dysregulation of HP. We would like to determine if HP of immature B cells is impaired and/or if inhibition of HP by peripheral B cells is more active in aged mice. These studies require lymphocyte transfers between young and aged mice and the analysis of developmentally regulated antigens by flow cytometry.



2. To attempt to suppress innate immune responses by using adenovirus to transfer genes encoding dominant-negative regulators of critical signal pathways. These studies will use cells from hCAR mice as targets and in vitro assays for proliferation and cytokine secretion to determine the effect of gene transfers.