Update 5/2013

Dr. Look has made a surpising and unprecedented discovery that most of T-ALL cells are addicted to the TYK2 pathways for their survival! Thus, his studies indicate that TYK2 kinase inhibition with small-molecule inhibitors will very likely lead to novel first-in-class therapies to improve the cure rate for T-ALL patients.

“The Bridge Grant enabled me to keep my lab team together, and the research itself on track, while I resubmitted an R01 research grant to the National Institutes of Health,” Look says. “The continuity it provided was essential. The research is now funded for a full five years.”

"We have worked on the development of novel druggable pathways that can provide new targets to significantly improve T-ALL therapies, and established the surprising and previously unprecedented discovery that most of T-ALL cells are addicted to the TYK2 pathway for their survival. TYK2 is one of the JAK family kinase proteins, which are intracellular mediators known to be involved in cell proliferation, survival, and differentiation, and abnormalities in JAK kinases are closely linked to the pathogenesis of hematological malignancies. We identified that TYK2 and its downstream effector STAT1 mediates T-ALL cell survival through the upregulation of pro-survival protein BCL2, and confirmed that the small-molecule inhibitors that are active against TYK2 effectively induce the death of T-ALL cells. Thus, our studies indicate that TYK2 kinase inhibition with small-molecule inhibitors will very likely lead to novel first-in-class therapies to improve the cure rate for T-ALL patients."