B cell receptor (BCR) endocytosis.

The B cell receptor (BCR) interacts with foreign antigens to mediate B cell activation and secretion of antibodies. B cell activation begins with initiation of signaling pathways, such as NFAT, NF-κB, and MAPK, and endocytosis of the BCR-antigen complex. Many studies have investigated the signaling pathways associated with BCR activation, and this work has led to significant advances in drug therapies to treat cancer and autoimmune diseases that are linked to aberrant BCR signaling.

Structurally distinct endocytic pathways for B cell receptors in B lymphocytes.

B lymphocytes play a critical role in adaptive immunity. On antigen binding, B cell receptors (BCR) cluster on the plasma membrane and are internalized by endocytosis. In this process, B cells capture diverse antigens in various contexts and concentrations.

A mevalonate bypass system facilitates elucidation of plastid biology in malaria parasites.

Malaria parasites rely on a plastid organelle for survival during the blood stages of infection. However, the entire organelle is dispensable as long as the isoprenoid precursor, isopentenyl pyrophosphate (IPP), is supplemented in the culture medium. We engineered parasites to produce isoprenoid precursors from a mevalonate-dependent pathway, creating a parasite line that replicates normally after the loss of the apicoplast organelle.

Development of a conditional localization approach to control apicoplast protein trafficking in malaria parasites.

Secretory proteins are of particular importance to apicomplexan parasites and comprise over 15% of the genomes of the human pathogens that cause diseases like malaria, toxoplasmosis and babesiosis as well as other diseases of agricultural significance. Here, we developed an approach that allows us to control the trafficking destination of secretory proteins in the human malaria parasite Plasmodium falciparum. Based on the unique structural requirements of apicoplast transit peptides, we designed three conditional localization domains (CLD1, 2 and 3) that can be used to control protein trafficking via the addition of a cell permeant ligand.