Biomedical Research Education & Training
Faculty Member

Macara, Ian G, Ph.D.
Chair of the Department of Cell & Developmental Biology
Professor of Cell & Developmental Biology
Louise B. McGavock Chair

Lab Url: https://medschool.vanderbilt.edu/macara-lab/

Phone Number: 615-875-5565 Lab 615-343-4143

Email Address: ian.g.macara@vanderbilt.edu

Macara, Ian's picture
Academic history
B.Sc. Biochemistry (1st Class Special Honors), University of Sheffield, UK
Ph.D. Biochemistry, University of Sheffield, UK
Postdoctoral Training, Brandeis University
Postdoctoral Training, Harvard University

Office Address   Mailing Address

Office U 3209 MRB III Labratory U 3200 MRB III

465 21st Avenue South U 3209 MRB III 37232-8240


Research Keywords
Cell polarity Breast cancer Epithelia Polarization Morphogenesis miRNA Mammary gland Cell biology DNA repair Septins,Cancer,Developmental biology,Signal transduction,Stem cells

Research Specialty
Research focuses on mammary gland morphogenesis, as well as breast cancer initiation and metastasis, and on the role of septins in cell polarity and in DNA repair.

Research Description
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
Lohia M, Qin Y, Macara IG.. The Scribble polarity protein stabilizes E-cadherin/p120-catenin binding and blocks retrieval of E-cadherin to the Golgi.. PLoS One, e51130(7(11)), doi:10.1371, 2012

McCaffrey LM, Montalbano J, Mihai C, Macara IG.. Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis.. Cancer Cell, 22(Nov 13), 601-14, 2012

McCaffrey, LM, Macara, IG. Signaling pathways in cell polarity. Cold Spring Harb Perspect Biol, 4(6), 2012

Petkowski JJ, Schaner Tooley CE, Anderson LC, Shumilin IA, Balsbaugh JL, Shabanowitz J, Hunt DF, Minor W, Macara IG.. Substrate specificity of mammalian N-terminal ??-amino methyltransferase NRMT.. Biochemistry, 51(30)(Jul 31), 5942-50, 2012

Iioka, H, Loiselle, D, Haystead, TA, Macara, IG. Efficient detection of RNA-protein interactions using tethered RNAs. Nucleic Acids Res, 39(8), e53, 2011 PMCID:3082893

Kim, JY, Oh, MH, Bernard, LP, Macara, IG, Zhang, H. The RhoG/ELMO1/Dock180 signaling module is required for spine morphogenesis in hippocampal neurons . J Biol Chem, 286(43), 37615-24, 2011

McCaffrey, LM, Macara, IG. Epithelial organization, cell polarity and tumorigenesis. Trends Cell Biol, 21(12), 727-35, 2011 PMCID:3182019

Pasic, L, Eisinger-Mathason, TS, Velayudhan, BT, Moskaluk, CA, Brenin, DR, Macara, IG, Lannigan, DA. Sustained activation of the HER1-ERK1/2-RSK signaling pathway controls myoepithelial cell fate in human mammary tissue. Genes Dev, 25(15), 1641-53, 2011 PMCID:3182019

Hao, Y, Du, Q, Chen, X, Zheng, Z, Balsbaugh, JL, Maitra, S, Shabanowitz, J, Hunt, DF, Macara, IG. Par3 controls epithelial spindle orientation by aPKC-mediated phosphorylation of apical Pins. Curr Biol, 20(20), 1809-18, 2010 PMCID:2963683

Qin, Y, Meisen, WH, Hao, Y, Macara, IG. Tuba, a Cdc42 GEF, is required for polarized spindle orientation during epithelial cyst formation. J Cell Biol, 189(4), 661-9, 2010 PMCID:2872902

Tooley, CE, Petkowski, JJ, Muratore-Schroeder, TL, Balsbaugh, JL, Shabanowitz, J, Sabat, M, Minor, W, Hunt, DF, Macara, IG. NRMT is an alpha-N-methyltransferase that methylates RCC1 and retinoblastoma protein. Nature, 466(7310), 1125-8, 2010 PMCID:2939154

Macara, IG, Iioka, H, Mili, S. Axon growth-stimulus package includes local translation. Nat Cell Biol, 11(8), 919-21, 2009 PMCID:2877918

McCaffrey, LM, Macara, IG. The Par3/aPKC interaction is essential for end bud remodeling and progenitor differentiation during mammary gland morphogenesis. Genes Dev, 23(12), 1450-60, 2009 PMCID:2701573

McCaffrey, LM, Macara, IG. Widely conserved signaling pathways in the establishment of cell polarity. Cold Spring Harb Perspect Biol, 1(2), a001370, 2009 PMCID:2742088

Mili, S, Macara, IG. RNA localization and polarity: from A(PC) to Z(BP). Trends Cell Biol, 19(4), 156-64, 2009 PMCID:2844668

Dorfman, J, Macara, IG. STRADalpha regulates LKB1 localization by blocking access to importin-alpha, and by association with Crm1 and exportin-7. Mol Biol Cell, 19(4), 1614-26, 2008 PMCID:2291406

Eisinger-Mathason, TS, Andrade, J, Groehler, AL, Clark, DE, Muratore-Schroeder, TL, Pasic, L, Smith, JA, Shabanowitz, J, Hunt, DF, Macara, IG, Lannigan, DA. Codependent functions of RSK2 and the apoptosis-promoting factor TIA-1 in stress granule assembly and cell survival. Mol Cell, 31(5), 722-36, 2008 PMCID:2654589

Hao, Y, Macara, IG. Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1. J Cell Biol, 182(5), 827-36, 2008 PMCID:2528582

Macara, IG, Mili, S. Polarity and differential inheritance--universal attributes of life. Cell, 135(5), 801-12, 2008 PMCID:2844324

Mili, S, Moissoglu, K, Macara, IG. Genome-wide screen reveals APC-associated RNAs enriched in cell protrusions. Nature, 453(7191), 115-9, 2008 PMCID:2782773

Zhang, H, Macara, IG. The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase. Dev Cell, 14(2), 216-26, 2008 PMCID:2768076

Goldstein, B, Macara, IG. The PAR proteins: fundamental players in animal cell polarization. Dev Cell, 13(5), 609-22, 2007 PMCID:2964935


Postdoctoral Position Available
Yes

Postdoctoral Position Details
Postdoctoral positions are available to work on several exciting projects associated with mammary gland morphogenesis, stem cells and breast cancer, epithelial polarization mechanisms, and on the linkage between septins and DNA repair. Applicants with strong publication records and experience working with mice and/or live cell imaging are encouraged to apply.

Updated Date
08/15/2013