Achievement

Kayleigh MacMaster and Christine Pallino are studying Shiga toxin (Stx). Stx producing E. coli (STEC) cause 100,000 US cases of disease annually with 10% leading to life-threatening hemolytic uremic syndrome (HUS). Stx has an ezymatically active A-subunit and B-subunits that activate signaling pathways after binding. Two antigenic variants, Stx1 and Stx2, share ~60% identity but Stx2 is associated with progression to HUS, possibly because of different cellular signaling cascades upon binding. Christine focuses on the toxins themselves and how subunits interact to bind to the membrane. Kayleigh studies differences in signaling pathways activated by B-pentamers binding the membrane and how these affect cellular signaling components. This includes a genome wide siRNA screen using primary human kidney cells. They will create endothelial cell lines expressing shRNA’s by lentiviral transfection and use these cells to understand how Stx affects these cellular kinases during infection.