Katie Alfare
Email: alfare@chem.wisc.edu
Katie Alfare graduated with a BA
in Chemistry from Franklin & Marshall College in Lancaster, PA in 2003 and
joined the Kiessling lab later that year. Her current research involves a receptor
called DC-SIGN (dendritic cell-specific intracellular adhesion molecule 3 [ICAM-3]-grabbing
non-integrin), found on the surface of dendritic cells. Dendritic cells play
an integral role in the immune system by harboring and degrading foreign microorganisms
and then displaying the antigens to T lymphocytes to initiate the immune response.
Several transmembrane receptors expressed on dendritic cells are involved in
these functions, including DC-SIGN. This receptor is involved in both antigen
uptake and in T lymphocyte-dendritic cell interactions. Specifically, DC-SIGN
has been found to bind HIV-1 envelope glycoproteins. - The binding of HIV-1
virus leads to its preservation, and subsequent presentation to T-lymphocytes.
As a consequence, DC-SIGN enhances the trans -infection of T cells.
The mechanism by which HIV-1 bypasses degradation by dendritic cells is unknown,
making DC-SIGN an interesting target for study. In addition, we are interested
in studying the mechanism of internalization utilized by DC-SIGN. DC-SIGN is
a C-type lectin, a class of Ca 2+ -dependent carbohydrate-binding proteins,
and is known to bind mannosides. Consequently, we are working on the synthesis
of a library of potential DC-SIGN inhibitors that will utilize a glycomimetic
scaffold, shikimic acid, which bears strong structural similarity to mannose.