Li Lily Wang, PhD
Microbiology and Molecular Genetics & Cancer Center
Medical College of Wisconsin
Research Focus: Immune regulation mediated by negative checkpoint regulators; Cancer immunotherapy
PhD: Dartmouth Medical School (2003) Biochemistry
The adaptive immune response requires T cells being stimulated by antigen presenting cells (APC) that present the cognate antigens. The antigen presentation process is highly regulated by a number of co-stimulatory and co-inhibitory molecules. Their integrated outcomes determine T cell activation, differentiation, and function.
The B7 family co-signaling molecules belong to the Ig superfamily.
Among them, co-stimulatory receptors, such as CD28 and ICOS, provide critical co-stimulatory signals that are required for T cell activation. On the other hand, co-inhibitory receptors, such as CTLA4, PD1, and orphan ligands such as B7H3 and B7H4, down-regulate TCR signaling and T cell responses. These co-inhibitory molecules are collectively called “immune-checkpoint regulators”. They play critical roles in maintaining peripheral tolerance, control autoimmunity, and immune responses against infection and cancer.
Wang Lab recently discovered a novel immune-checkpoint molecule, called V-domain Immunoglobulin Suppression of T cell Activation (VISTA). Our first study has established that VISTA engages an unknown receptor on T cells to directly suppress T cell activation (J Exp Med, 2011, 208(3):577-92).
We believe that similar to other immune checkpoint regulators such as CTLA-4 and PD-1, VISTA critically regulates immune responses against self and foreign antigens. As such, targeting VISTA is a promising approach for treating autoimmunity, infectious disease and cancer.
Specifically, we ask these questions:
How does VISTA regulate peripheral tolerance and autoimmunity in the face of other immune-checkpoints such as PD-1. Can VISTA collaborate/synergize with other immune checkpoints?
How does VISTA directly suppress TCR signaling, which promotes T cell exhaustion and tolerance in disease settings such as cancer and chronic viral infection?
What is the unique function of VISTA as a ligand, as well as a potential receptor when expressed on various immune cell types?
How to target VISTA for cancer immunotherapy, i.e. by testing optimal combinatorial strategies, including chemotherapy, radiation, vaccine, and other co-stimulatory and co-inhibitory reagents.
How to enhance VISTA-mediated immune suppression for treating inflammatory diseases.
VISTA blocking antibody synergizes with a tumor vaccine