Epigenetic Mechanisms in Breast Cancer

Breast cancer is one of the most commonly diagnosed maladies in women. In 2018, according to the American Cancer Society, more than 270,000 new cases of invasive breast cancer will be diagnosed in the US. Breast cancer is a heterogeneous disease originating from the basal and luminal cells of the mammary glands. Each of these subtypes has different risk factors for disease incidence, response to treatment, risk of progression, and preferential organ sites of metastases. Therefore, understanding the specific molecular and epigenetic mechanisms that control the oncogenic pathways deregulated in the different subtypes of breast cancer is crucial for the development of new therapeutic strategies.

Pluripotency and Differentiation

The potential to generate specific cell types capable of replacing damaged or aged human tissue is the vision of regenerative medicine. Human induced pluripotent stem cells (hiPSCs) hold promise to fulfill this vision, as they display the potential to differentiate into any specific cellular lineage. Despite tremendous advances, the molecular and epigenetic mechanisms that control hiPSCs pluripotency and cellular fate decisions remain poorly defined. We and others demonstrated previously that Polycomb-group proteins (PcG) orchestrate cell fate decisions and pluripotency in mouse embryonic stem cells (mESCs).  However, the mechanisms whereby Polycomb proteins control pluripotency in human cells and drive stem cell differentiation into distinctive cell types remain largely unknown.

Chromatin Architecture in Stem Cells and Cancer

Chromatin structure is emerging as an important regulator of gene expression, cell fate determination and cancer progression. We are investigating the chromatin dynamics imposed by Polycomb complexes in stem cells and cancer models.

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