Mincle Adjuvant Development
The Macrophage-Inducible C-type Lectin receptor (Mincle) plays a critical role in innate immune recognition and pathology, and therefore represents a promising target for vaccine adjuvants. Innovative trehalose-based Mincle agonists with improved pharmacology and potency may prove useful in the development of Th17-mediated adaptive immune responses. Our group focuses on the design of small symmetric and asymmetric trehalose-based adjuvants for targeting the Mincle receptor.
Syk-Raf Adjuvant Discovery
The syk-raf project will target small molecules that induce Th17 or Th17/Th1 immunity as adjuvants for bacterial and fungal pathogens. Specifically, the chemistry group will focus on the discovery of synthetic putative CLR agonists through validation and resynthesis of the high throughput screen hit molecules and construct three differnet classes of small library molecules thorugh a directed synthetic approach.
Antagonist
Pattern recognition receptors (PRRs) recognize small ligands to activate an intracellular immune response for protection. Traditionally, our group has focused on the design and evaluation of small molecules have been designed for this purpose to protect against pathogens. While there has been a large focus on small molecules that target and activate certain PRRs, identification of small molecules that can attenuate or block certain PRR-mediated intracellular signaling has lagged. We have observed that our ligands with small chemical changes are playing an astounding role on if intracellular signaling is observed or not (specifically, interleukin-6 cytokine response). However, there is a lack of knowledge surrounding how and why small chemical changes in ligands have a significant impact on PRR-mediated intracellular signaling. This work project uses our functionally diverse ligands to evaluate the small molecule-protein interactions through collaboration with the University of Montana’s Center for Biomolecular Structure and Dynamics core facilities.