Research Overview

Our lab studies the regulatory signals of mammary stem cell self-renewal and the interaction between stem cells and their niche. The mouse mammary gland provides an excellent system to study those. Unlike other mammalian organs that develop in the embryonic stage, mammary gland develops mostly post-natally. Mammary gland is the only epithelium organ that is able to completely regenerate after transplantation, which serves as a stringent in vivo assay to examine the adult stem cell properties, self-renewal and the capability to differentiate.

We are particularly interested in understanding the mechanisms through which the self-renewal is maintained. We focus our efforts on Wnt signals that are critical for many stages of mammary development and are established as a self-renewal niche signal. We are also enthusiastic about identifying new niche components and signals within which.

Our long-term goal is to determine how the stem and progenitor cell regulatory mechanisms have deviated in breast cancer, and to learn how to control the players in these machineries for the purposes of regenerative and cancer medicine.

Intrinsic Stemness Mechanisms

The decision of stem cells to self-renew or differentiate is regulated at multiple levels, including cell-intrinsic transcriptional programs and extra-cellular signals originating from a specialized niche.

We previously established that Wnts promote the self-renewal of mammary stem cells. Furthermore, we developed a method to culture and expand mammary stem cells in vitro for a long period with the maintenance of their full development potential. We determine to understand the molecular mechanism through which Wnt signaling maintains and promotes stem cell self-renewal. To this end, we are interested in identifying the stemness gene among the Wnt targets in mammary stem cells and study the function of their encoded proteins. This work has led to identify a novel membrane protein that is critical in maintaining the stem cell properties. A major challenge in adult stem cell biology is to bear with the heterogeneity of the stem cell-enriched population, hoping for the essential signals that are activated in only a small population of cells would not be buried in the noise. We envision that our approach will enable us not only to decipher the molecular mechanism through which stemness is maintained, but also discover de novel stem cell marker for isolation of pure mammary stem cells.

Stem Cell and The Niche

Current niche theory portraits stem cell being permissive to receive signals from the niche and enter cell cycle for self-renewal or differentiation. We hypothesize that stem cells may play an instructive role as well when interact with their niche. To this end, we set to identify novel secretary signals from the stem cells and study their cross-talk with the known niche factors. We also explore other niche components in the stroma, such as immune cells and endothelial cells and their functions in mammary development and regeneration process.project2-450X150-rounded

Cell Lineage and Cancer

project3-120X150-rounded 1Breast cancers have various cellular origins and are triggered in different developmental time windows. With the aim to study critical players that participate in normal development and investigate how they are deviated in pathological conditions, we employ genetic lineage tracing experiments in mouse model to thoroughly examine the gene’s function in lineage commitment and cell fate decision. The decision is further examined in pathological challenges induced by genetic mutation or hormones stimulation etc.

In addition to animal models, we collaborate with local breast oncologists and surgeons to study human breast stem cell and tumor-initiating cells in breast caner. We aim to identify critical genes and potential therapeutic targets against breast cancer.