Viral-host interactions

In addition to the virally encoded enzymes required for replication and assembly, HIV-1 expresses a collection of accessory proteins that lack intrinsic enzymatic activity but which are essential for disease pathogenesis by dysregulating host cell enzymatic activities to counterattack the host antiviral response and promote virus replication. In particular, the HIV-1 accessory protein Nef is required for the efficient onset of AIDS following HIV-1 infection. Nef modifies the host cellular environment in many ways, including alteration of T cell activation, modulation of apoptotic and autophagic pathways, as well as disrupts the intracellular trafficking of MHC-I and other cell surface molecules of helper T cells and macrophages. Our laboratory is interested in the various interactions between HIV-1 viral accessory proteins and host cellular partners and how these interactions modulate membrane trafficking pathways to evade the immune system.

Membrane trafficking

We also study the fundamental mechanisms governing membrane trafficking in uninfected cells. Here, we developed critical tools to track and define protein-protein interactions within cells (Dirk et al, PLoS One 2015) and we have studied the mechanism enabling the PACS-1 membrane trafficking protein to mediate protein trafficking to dense core secretory granules (Dirk et al., BBRC 2018). We have continued our fundamental cell biology studies to define the nuclear protein targeting signals located within PACS-1 (Trothen and Zang et al., FEBS Letters 2022). These studies defined a novel PACS-1 nuclear protein binding partner, the RNA binding protein PTBP1, identifying a novel role for PACS-1 in RNA-binding protein trafficking. Overall, our these studies seek to identify the key roles undertaken by the PACS-1 and PACS-2 membrane trafficking proteins.