The focus of our laboratory is the study of protein movement within cells. We are currently exploring the diverse projects below.

• Our studies define how the HIV-1 accessory proteins Nef and Vpu interact with host cellular partners to ensure an optimal cellular environment where HIV-1 can thrive and thwart the immune response. Nef and Vpu are multifunctional viral proteins able to interact with multiple host proteins. As Nef and Vpu are membrane anchored or transmembrane proteins, they often interact with membrane-bound proteins, or receptors, and concomitantly modifies their cellular localisation. Effectively, host protein mis-localisation by Nef and Vpu a key mechanisms utilized by HIV to evade the human immune response, and effectively ensure viral pathogenesis.

• We are interested in the specific viral factors contributing to decay of the latent viral reservoir, a subset of infected cells that persist despite current antiretroviral therapy regimes. Previously, we determined that Nef-mediated MHC-I downregulation may contribute to latent reservoir dynamics (Mumby et al. 2025). We are now investigating whether the targeting of Nef-mediated immune evasion mechanisms can help eliminate this population of HIV-1 infected cells that persist despite treatment and whether other viral protein functions also contribute to decay of latently infected cells.

• Additionally, we use ancestral reconstruction to understand the evolution of HIV-1 accessory proteins as the virus evolved from simians to humans, with the overall goal of understanding viral evolution and how this contributes to disease pathogenicity. With this model, we determined that Nef-mediated modulation of T cell activation contributed to the increased pathogenicity of HIV-1 as it evolved from its simian precursors (Baldino et al. 2025) and are now investigating the evolution of other viral protein functions in diverse SIV and HIV types.

• Highly Pathogenic Avian Flu Viruses (HPAI): Funded by the Canadian government as part of the Prepare, React, Collect, Innovate, Share, and Engage (PRECISE) initiative – a multi-institution and multi-disciplinary partnership aimed at developing a rapid-response pipeline for emerging pandemics – focuses on developing animal models to characterize the pathogenesis of emerging influenza A infections within CL3 settings, and on characterizing host immune responses to infection, which can inform antiviral and vaccine design.

• We also study the fundamental mechanisms governing membrane trafficking in uninfected cells. 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 also 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, these studies seek to identify the key roles undertaken by the PACS-1 and PACS-2 membrane trafficking proteins.