Lawrence P. Kane, PhD

A major focus of my lab has been in the study of how T cell activation is regulated by the TIM family of proteins. We are currently focused on understanding how Tim-3 transmits signals that augment or inhibit T cell activation. Over the past several years, we have expanded our efforts in this area to include the in vivo effects of Tim-3 signaling, using both mouse models and human samples from cancer patients. This work is now leveraging a multi-disciplinary approach to reveal important molecular pathways linked to Tim-3 function.

We have generated several genetic models to study Tim-3, including cell-type-specific inducible models of Tim-3 expression and knockout. We have used these models, in conjunction with infection with LCMV, using both an acute/memory strain and a strain that mimics the effects of chronic infection. In recent years, we have also been studying Tim-3 function in the context of murine and human tumors.

An interest in Akt signaling led to the study of a negative regulator of PI3K signaling known as Pik3ip1 or TrIP. We have generated novel tools to study this protein, including an inducible KO mouse model and a mAb specific for mouse TrIP. We are currently actively investigating the biochemical basis for TrIP function, as well as its role in regulating T cell responses in vivo. We recently discovered that specific KO of TrIP in CD8+ T cells leads to significant enhancement of T cell responses, which we hypothesize is due to effects on early T cell activation.