Zhu Wang

We are interested in understanding cell type specification, stem cell differentiation, and cancer initiation in vivo, with a particular focus on the urogenital system. Multiple experimental approaches are employed, including mouse models, genetic lineage tracing, organoid culture, molecular and cell assays, and single cell and bioinformatic analyses. Ultimately, a better understanding in this field will facilitate prevention and treatment of diseases such as prostate and bladder cancers.

Mechanism of prostate basal stem cell plasticity

Prostate epithelial basal cells behave as adult stem cells to produce luminal cells in organogenesis, but basal stem cell activities are significantly restricted as prostate matures. Interestingly, basal-to-luminal differentiation is greatly enhanced under oncogenic or inflammatory conditions. Are those basal cells reprogrammed to a state resembling the early postnatal basal stem cells? We are dissecting the extrinsic signaling pathways and the internal program that regulate the stem cell plasticity of prostate basal cells in vivo.

Roles of AR and Nkx3.1 in prostate homeostasis and cancer

Androgen regulates numerous aspects of prostate physiology and diseases through the transcription factor androgen receptor (AR). Despite the use of androgen-deprivation therapy (ADT) in the clinics, prostate cancer almost always relapses after treatment. This can be partially attributed to the distinct roles of AR in different cell types of the organ. We recently dissected the roles of AR in different cell types of the prostate epithelium, including its role in specifying a type of luminal stem cell CARN, which is marked by Nkx3.1 expression after ADT. We are also analyzing the role of stromal AR in modulating prostate cancer progression.

Novel mouse bladder cancer models

The bladder shares many similarities with the prostate in cellular organization. The mutational landscape of human bladder cancer is complex, yet there is a relative lack of mouse bladder cancer models compared to many other cancers. We are using CRISPR to build novel bladder cancer mouse models, with the aim to understand its cell of origin and the roles of key tumor suppressor genes.

 

Lineage tracing analysis shows that adult prostate basal cells require cell-autonomous AR (red) for luminal differentiation (arrow).