Mechanisms of HIV-1 Control and Pathogenesis
The natural history of HIV infection is highly heterogeneous in different individuals, spanning from a stable asymptomatic condition to a rapid disease evolution. A major determinant of the pace of HIV disease progression is the in vivo level of viral replication, which is regulated by an intricate network of bioactive molecules, including both soluble immune modulators and cell-associated receptors. My research aims to precisely delineate the molecular mechanisms of HIV-1 control and pathogenesis, underlying interactions between soluble and cell-derived molecules with the HIV-1 envelope, with a goal of identifying new vulnerabilities on the virus that may lead to novel targets for therapy and prevention.
Novel Cytokine Expression Patterns
It has been well established that cytokines have extraordinary potential as ‘immunological multi-taskers’. These small molecular weight proteins can be expressed via a variety of stimuli, in a multitude of cell types throughout the body, and can elicit a broad range of responses. Key features of cytokines, such as glycosylation and positioning of charged domains, can drastically influence biological functions, protein stability, protein-protein interactions (oligomerization), and receptor engagement.
Interestingly, some cytokines can even be stored at high concentrations, preformed inside producer cells, awaiting rapid release without requiring de novo synthesis, resulting in high-speed immune responses. While much work is centered on downstream functions of cytokines, we seek to understand earlier events in the expression, secretion, and interplay among these proteins, in an effort to establish how cytokines are regulated in a normal-functioning immune system, before disease disrupts the equilibrium.