Li Lily Wang, PhD

Assistant Professor
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

Wang Laboratory

The adaptive immune response requires T cells being stimulated by antigen presenting cells (APC) that present the cognate antigens. The interaction between APC and T cells is highly regulated by a number of co-signaling molecules. Their integrated outcomes determine T cell activation, differentiation, and function (Figure 1).

Li Lily Wang, PhD
Figure 1. T cell activation upon interaction with antigen presenting cells

The B7 family co-signaling molecules belongs to the Ig superfamily (Figure 2). 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 T cell responses. These inhibitory molecules are called “immune-checkpoint regulators”. They play critical roles in maintaining peripheral tolerance, control autoimmunity, and immune responses against infection and cancer.

Li Lily Wang, PhD
Figure 2. The B7 family of co-stimulatory and co-inhibitory molecules

Dr Lily Wang, through her earlier work, has identified a novel immune-checkpoint molecule, called V-domain Immunoglobulin Suppression of T cell Activation (VISTA) (Figure 3).

Recent studies from out lab and others have established that:

  • VISTA pathway directly suppresses T cell activation.
  • Aged VISTAKO mice developed spontaneous T cell activation and multi-organ chronic inflammation indicating a loss of peripheral T cell tolerance.
  • Young VISTAKO mice show T cell hyper-activation towards foreign antigens. Consistently, monoclonal antibody targeting VISTA enhanced endogenous or vaccine-induced anti-tumor T cell responses (Figure 4).


Sequence of the Ig-v domain

Figure 3. V-domain Immunoglobulin Suppressor of T cell Activation


VISTA blocking antibody synergizes with a tumor vaccine

Figure 4. VISTA-specific monoclonal antibody synergized with cancer vaccine and promoted tumor clearance in murine tumor models

We hypothesize 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. Our future studies will focus on addressing the following questions:

  1. How does VISTA regulate peripheral tolerance and autoimmunity, synergistically together with other immune-checkpoints?
  2. What are the molecular mechanisms of VISTA pathway, when functions as a ligand or a receptor, on various immune cell types, such as T cells and myeloid antigen present cells.
  3. Therapeutic development:
    • 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 and autoimmune diseases.

Recent Publications


Contact Information

Li Lily Wang, PhD
Department of Microbiology and Molecular Genetics
Medical College of Wisconsin
8701 Watertown Plank Road
Milwaukee, WI 53226

(414) 955-7489

Office  BSB-204 (Basic Science Building)
Lab  BSB-215 (Basic Science Building)


Medical College of Wisconsin
8701 Watertown Plank Road
Milwaukee, WI 53226
(414) 955-8296
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Page Updated 11/09/2015