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Dr. Luke McCaffrey’s laboratory studies how cell polarity controls epithelial morphogenesis, cancer progression and stem cell renewal.

His team has two research areas:

1) Epithelial morphogenesis – The development of epithelial tissues that line body surfaces requires the coordinated action of several cellular processes, including proliferation, apoptosis, directed cell motility, stem cell renewal, and differentiation. These processes require a high degree of organization within individual cells, which is coordinated between cells during development. A protein complex, consisting of Par3, Par6 and aPKC, is a crucial organizer of cell polarity and Dr. McCaffrey has demonstrated an essential role for this complex in organization and differentiation during mammary gland morphogenesis.

To understand the role of polarity signaling in mammary gland morphogenesis, Dr. McCaffrey’s group uses lentivirus to transduce mammary stem cells to either over-express or silence the expression of specific polarity proteins by RNA-interference. Following transplantation of the stem cells back into a mouse they assess the effects on epithelial tube morphogenesis. To understand how cell polarity regulates the dynamics of cell motility and cell division during epithelial morphogenesis, Dr. McCaffrey uses time-lapse confocal microscopy of 3-D organotypic cultures derived from mammary glands to complement the use of mouse models. These cultures retain many features of the intact tissue, including the presence of multiple cell types.

2) Tumor initiation, growth, invasion, and metastasis – Accumulating evidence demonstrates that a common characteristic of malignant transformation is the loss of epithelial polarity and organization. Dr. McCaffrey’s research is looking directly at human breast cancer samples to understand what components of epithelial polarity are disrupted in breast and ovarian cancer progression.

Using 3D culture assays and in vivo models, Dr. McCaffrey’s team examines how disrupting specific cell polarity proteins cooperates with oncogenes to drive tumorigenesis and metastasis. Dr. McCaffrey found that disruption of the Par/aPKC polarity complex promotes cancer cell invasion and metastasis. His group will continue to identify how polarity complexes regulate cell signaling in tumor cells to control cancer progression.

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