This proposal outlines a 5-year training program for the development of an academic career in Pediatric Infectious Disease. The candidate has completed residency training in Pediatrics, Ph.D. training in Molecular and Cell Biology, and fellowship training in Infectious Disease. She is now in the midst of enhancing her scientific skills through a unique blend of interdepartmental resources and expertise. ? ? The candidate's goal is to develop a command of cellular immunology as it relates to viruses by integrating EBV immunology research and a structured curriculum to enhance scientific knowledge in the fields of both virology and cellular immunology. Dr. George Miller, a renowned EBV virologist will mentor the candidate's scientific development. To enhance the experience, an advisory committee of highly respected immunologists studying diverse aspects of cellular immunology will provide scientific and career guidance. ? ? The candidate's research will examine the immune responses in the early stages of primary EBV infection and in the early stages of control of outgrowth of latently infected B cells in EBV-immune individuals. These questions will be addressed using a relevant and unique model experimental system that the candidate has developed. The goals are: 1. To identify the cells important in the initial response to EBV-LCL during primary infection and for the prevention of outgrowth of latently infected B cells in EBV seropositive individuals. 2. To determine if the responding cells are cytotoxic to LCL and characterize the mechanism of cell killing. 3. To experimentally modulate the composition and nature of the immune response by using exogenous molecules. This study will, for the first time, allow glimpses into the earliest interactions between the immune system and EBV without modification or amplification of the immune response. It is also expected to enhance the understanding of EBV lymphoproliferative diseases and have potential diagnostic and therapeutic implications. ? ?
