Dr. Weiping Zou
Dr. Weiping Zou is the Charles B. de Nancrede Professor of Surgery, Immunology and Biology and Director for Translational Research at the University of Michigan. The research interests of the Zou lab are in tumor immunopathology and immunotherapy, with an emphasis on the cross-talk among immune cell subsets, stromal cells, tumor cells and tumor stem cells in the tumor microenvironment, and its impact on tumor immunity, tolerance and therapy.

1: Treg cells and tumor: A regulatory T cell (Treg cell) is functionally defined as a T cell that inhibits an immune response by influencing the activity of another cell type. The most well-defined Treg cells are CD4+CD25+FOXP3+ T cells. The Zou lab has systematically demonstrated the phenotype, function and clinical relevance of Treg cells in human cancer, and was one of the first groups to do so. In addition to classic CD4+CD25+FOXP3+ Treg cells, the lab has also defined a CD8+ regulatory T cell population in human cancer. Further, the lab has defined the molecular mechanisms by which Treg cells traffic to the tumor environment and bone marrow. Chemokines and chemokine receptors (e.g. CCL22/CCR4, CXCL12/CXCR4) play crucial roles in directing Treg cell migration and homing. The lab is currently focusing its efforts on determining the detailed mechanistic interaction between Treg cells and other immune cells in the tumor environment, the potential regulatory effects of steroid hormones on Treg cell differentiation and function, and the pathological relevance of Treg cells in tumor bone marrow metastasis. In collaboration with UM oncologists and industry, the group will test small molecules to block Treg cell tissue/organ-specific homing and has clinical trials targeting Treg cells in patients with cancer.

2: Th17 cells and tumor: IL-17+CD4+ T cells (Th17 cells) play an active role in inflammation and autoimmune diseases. However, the nature of Th17 in the context of tumor immunity remains unknown.  IL-17+ T cells including CD4+ and CD8+ T cells are kinetically induced in multiple tumor microenvironments in mice and humans, and IL-2 and IL-1 play opposite roles in IL-17+ T cell differentiation in the tumor microenvironment. The lab is currently focusing on defining the phenotype, differentiation, regulation, interaction with other cells, and function of IL-17+ T cells in human and murine tumors.

3: B7 family members and tumor: Antigen presenting cells (APCs) are a heterogeneous group of immune cells that display differences in anatomic localization, cell surface phenotype, and function. B7.1 (CD80) and B7.2 (CD86) are B7 family members with stimulatory functions for T cell activation. B7-H1 (PD-L1) and B7-H4 (B7s, B7x) are newly-identified B7 family members. The laboratory has phenotypically and functionally studied different subsets of APCs including myeloid dendritic cells, plasmacytoid dendritic cells, macrophages and myeloid suppressor cells in the tumor environment.  The Zou group has shown that tumor associated APCs highly expressed B7-H1 or B7-H4, and these B7-H1+ or B7-H4+ APCs temper tumor specific T cell function. The laboratory is currently focusing its efforts on determining the detailed molecular signal pathway for regulating these inhibitory B7 family members and their potential therapeutic relevance. In collaboration with UM oncologists and industry, the group will test small molecules to block inhibitory B7 molecules in patients with cancer.

4: Inflammation and tumor: Inflammation plays a crucial role in tumor pathology. The Zou group is investigating the cellular and molecular mechanisms of chronic inflammation at tumor initiation, development and metastasis in patients with cancer and in specific animal models.  In collaboration with UM stem cell biologists, the lab will focus their efforts on defining the role of interaction between inflammatory immune cells and tumor stem cells in tumor stem cell transformation and tumor development.