[1] Since 2004, he has been the president and CEO of Lankenau Institute for Medical Research, a cancer-focused research center in the U.S.[2][3][4] He is also the co-director of the Program in Cancer Cell Biology & Signaling at the Sidney Kimmel Cancer Center, Thomas Jefferson University.

[11][12] In 2002, he moved his groups at Wistar and DuPont to the Lankenau Institute for Medical Research (LIMR) and became the president and CEO there in 2004.

[14][15][16][17] Prendergast's current research focuses on new uses of IDO1 inhibitory drugs in medicine, investigations of the IDO2 enzyme in cancer and autoimmunity, and therapeutic antibodies that target the disease severity modifier genes Bin1 and RhoB to broadly treat autoimmune disorders and diabetic complications.

His research team pioneered the early discovery and development of experimental drugs that inhibit the tryptophan catabolizing enzyme IDO1 as a new type of oral immunotherapy for cancer,[18] currently under study worldwide.

[21] In 2018, Prendergast was named The Havens Chair in Biomedical Research by the Lankenau Medical Center Foundation.