Researcher | Research Overview
A virus enters a target cell by binding to its receptor on the cell surface, initiating a series of conformational changes that result in fusion of the viral and cellular membranes. Membrane fusion provides viral capsid and genome to access the cytoplasm, beginning the next round of replication.
One of the most important insights one can have about a virus derives from its cellular receptor. The Choe laboratory has identified the receptors and related entry cofactors for several clinically important viruses, combining biochemical, cell biological, and structural data. These include CCR5 and other coreceptors for HIV-1, ACE2 as the receptor for SARS-CoV, and TFR1 as the receptor for all New World hemorrhagic fever arenaviruses. In addition to receptor/coreceptor identification, we observed that tyrosine sulfation, a post-translational modification, is the sole common feature of all known HIV-1 coreceptors and essential for their coreceptor function. We also found lysosomal enzymes, cathepsins B and L, are essential for SARS-CoV entry, TIM1 is a general entry enhancing host factor for many viruses, and AXL mediates Zika virus infection of fetal endothelial cells, which could contribute to fetal microcephaly.
Applying our experience with viral entry, we recently developed an AAV vector significantly enhanced in its ability to transduce skeletal muscle, a useful property for intramuscular delivery of vaccines. We are currently developing AAV vectors and other vehicles that specifically target other types of cells including CD4+-T cells or B cells. In collaboration with the Farzan lab, my lab also seeks to improve anti-viral protein therapeutics, using B-cell engineering and a combined strategy of in vitro selection and natural in vivo maturation. In addition, my lab pursues to find strategies to minimize antibody-dependent-enhancement (ADE) of dengue virus infection with the goal of making a useful contribution to dengue vaccine development.
Researcher | Research Background
Hyeryun Choe received her PhD from Pennsylvania State University in Cellular and Molecular Biology and was trained as a postdoctoral fellow at Beth Israel Hospital in TFR1 receptor-mediated endocytosis and at Dana Farber Cancer Institute in HIV-1. She started her laboratory at Boston Children's Hospital, moved to the Florida Campus of The Scripps Research Institute, and returned to Boston Children's Hospital in 2023.