Profile

Our lab is interested in the ways in which cells break symmetry, and initiate and maintain spatial asymmetries. Asymmetries can form as cells polarize, or can occur within cells, for instance during mitosis. Gradients of proteins or other molecules can create asymmetries that the cell uses to specify orientations and subcellular locations. Carcinomas arise from epithelial cells, and tumor progression involves a loss of polarity, so an understanding of cell polarity is important in the identification of novel therapeutic approaches to cancer. Cell polarity is usually lost early during tumor progression, and several polarity proteins have been identified as tumor suppressors.
We have four major programs ongoing a?? on the mechanisms that determine the polarization of mammalian epithelial cells; on the control of mammary gland morphogenesis and breast cancer initiation and metastasis; on the role of septins in cell polarity and in DNA repair; and on RNA localization.
We use a range of approaches to study these cell processes, including a new mammary gland regeneration model in which mammary stem cells are transduced with lentivirus then transplanted into the cleared fat pads of recipient mice, where the cells regenerate an entire new mammary ductal tree. We have also developed new methods to purify RNA binding proteins, and to study miRNA function in mammary gland morphogenesis. In vitro studies include 3D culture of mammary gland organoids, human breast tissue organotypic cultures, and renal epithelial cysts. We are using these systems to explore the mechanisms that control spindle orientation during mitosis; the roles of small GTPases in cell polarization; and the mechanisms underlying asymmetric cell divisions of mammary stem cells.

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. The Par3 polarity protein is an exocyst receptor essential for mammary cell survival. Ahmed SM, Macara IG (2017) Nat Commun : 14867
    › Primary publication · 28358000 (PubMed) · PMC5379108 (PubMed Central)
  2. The Par3-like polarity protein Par3L is essential for mammary stem cell maintenance. Huo Y, Macara IG (2014) Nat Cell Biol 16(6): 529-37
    › Primary publication · 24859006 (PubMed) · PMC4083567 (PubMed Central)
  3. PTK7-Src signaling at epithelial cell contacts mediates spatial organization of actomyosin and planar cell polarity. Andreeva A, Lee J, Lohia M, Wu X, Macara IG, Lu X (2014) Dev Cell 29(1): 20-33
    › Primary publication · 24703874 (PubMed) · PMC4086913 (PubMed Central)
  4. Organization and execution of the epithelial polarity programme. Rodriguez-Boulan E, Macara IG (2014) Nat Rev Mol Cell Biol 15(4): 225-42
    › Primary publication · 24651541 (PubMed) · PMC4211427 (PubMed Central)
  5. The RNA-binding protein Fus directs translation of localized mRNAs in APC-RNP granules. Yasuda K, Zhang H, Loiselle D, Haystead T, Macara IG, Mili S (2013) J Cell Biol 203(5): 737-46
    › Primary publication · 24297750 (PubMed) · PMC3857475 (PubMed Central)
  6. The Scribble polarity protein stabilizes E-cadherin/p120-catenin binding and blocks retrieval of E-cadherin to the Golgi. Lohia M, Qin Y, Macara IG (2012) PLoS One 7(11): e51130
    › Primary publication · 23226478 (PubMed) · PMC3511384 (PubMed Central)
  7. Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis. McCaffrey LM, Montalbano J, Mihai C, Macara IG (2012) Cancer Cell 22(5): 601-14
    › Primary publication · 23153534 (PubMed) · PMC3500525 (PubMed Central)
  8. Substrate specificity of mammalian N-terminal α-amino methyltransferase NRMT. Petkowski JJ, Schaner Tooley CE, Anderson LC, Shumilin IA, Balsbaugh JL, Shabanowitz J, Hunt DF, Minor W, Macara IG (2012) Biochemistry 51(30): 5942-50
    › Primary publication · 22769851 (PubMed) · PMC3447998 (PubMed Central)
  9. NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein. Tooley CE, Petkowski JJ, Muratore-Schroeder TL, Balsbaugh JL, Shabanowitz J, Sabat M, Minor W, Hunt DF, Macara IG (2010) Nature 466(7310): 1125-8
    › Primary publication · 20668449 (PubMed) · PMC2939154 (PubMed Central)