Assistant Professor of MCD Biology
We are interested in understanding cell type specification, stem cell differentiation, and various cell behaviors in vivo, with a particular focus on the prostate gland. To tackle these questions, we employ multiple experimental approaches, including animal models, genetic lineage tracing, molecular and cell assays, and bioinformatic analyses. Ultimately, a better understanding in this field will facilitate prevention and treatment of diseases such as prostate cancer. Currently, the lab is focused on the following research areas:
Prostate basal stem cell plasticity
Prostate epithelial basal cells behave as adult stem cells to produce luminal cells during prostate organogenesis. However, in the mature prostate, basal stem cell activities are significantly restricted, and basal-to-luminal cell differentiation becomes rare. Interestingly, basal-to-luminal differentiation is greatly enhanced under oncogenic or inflammatory conditions. Are tumorigenic basal cells in a state similar to that of the young adult basal stem cells? We are dissecting the internal and extrinsic signaling pathways that regulate the stem cell plasticity of prostate basal cells.
AR and Nkx3.1 in prostate homeostasis and cancer
The male hormone androgen regulates numerous aspects of prostate physiology and cancer progression through the transcription factor androgen receptor (AR). Despite the use of androgen-deprivation therapy (ADT) in the clinics, prostate cancer almost always relapse after this treatment. This can be partially attributed to the distinct roles of AR in different cell types of the organ. We recently found AR to be cell-autonomously required for stem cell activities of basal stem cells as well as a type of luminal stem cell called CARNs. CARNs are distinguished by the expression of the gene Nkx3.1 in luminal cells after androgen deprivation. Being a transcriptional target gene of AR, Nkx3.1 encodes a key regulator of prostate cell fate specification and tumor suppressor. We are investigating the molecular mechanisms by which AR and Nkx3.1 orchestrate different cell behaviors in prostate homeostasis and cancer initiation.
Please follow this link to find the lab's publications in the National Library of Medicine's PubMed database.
A model for the cellular lineage relationship in prostate homeostasis and cancer initiation. For details see Wang et al. 2013 Nat Cell Bio. 15:274-283.