Ian G. Macara, Ph.D.



Visit Lab Site

Faculty Appointments
Chair of the Department of Cell and Developmental Biology Professor of Cell and Developmental Biology Louise B. McGavock Chair
Ph.D., Biochemistry, University of Sheffield, Sheffield, United KingdomB.Sc., University of Sheffield, Sheffield, United Kingdom
Office Address
465 21st Avenue South
U 3209 MRB III
Nashville, TN 37232-8240
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 research programs on:
(a) understanding the polarization machinery of mammalian epithelial cells
(b) control of epithelial homeostasis in mammary gland morphogenesis, breast cancer initiation and metastasis
(c) the role of stem cells and mechanisms controling stemness in the mammary gland and in breast cancer
(d) the role of a novel exonuclease in DNA repair of inter-strand crosslinks.
We use a range of approaches to study these cell processes, including a 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. In vitro studies include single molecule measurements of polarity complexes using TIRF microscopy and CRISPR gene-editing; genome-wide CRISPR screens for genes that regulate homeostais; 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, epithelial homeostasis, and multipotency versus unipotency in mammary stem cells.
Research Keywords
Breast cancer; stem cells; progenitors; morphogenesis; cell polarity; epithelia; DNA repair; tumor promoters; development; mammary gland
Archibald A, Mihai C, Macara IG, McCaffrey L. Oncogenic suppression of apoptosis uncovers a Rac1/JNK proliferation pathway activated by loss of Par3. Oncogene [print-electronic]. 2015 Jun 6/11/2015; 34(24): 3199-206. PMID: 25109337, PMCID: PMC4324374, PII: onc2014242, DOI: 10.1038/onc.2014.242, ISSN: 1476-5594.

Guyer RA, Macara IG. Loss of the polarity protein PAR3 activates STAT3 signaling via an atypical protein kinase C (aPKC)/NF-¿B/interleukin-6 (IL-6) axis in mouse mammary cells. J. Biol. Chem [print-electronic]. 2015 Mar 3/27/2015; 290(13): 8457-68. PMID: 25657002, PMCID: PMC4375497, PII: M114.621011, DOI: 10.1074/jbc.M114.621011, ISSN: 1083-351X.

Iioka H, Macara IG. Detection of RNA-Protein Interactions Using Tethered RNA Affinity Capture. Methods Mol. Biol. 2015; 1316: 67-73. PMID: 25967053, DOI: 10.1007/978-1-4939-2730-2_6, ISSN: 1940-6029.

Macara IG, Guyer R, Richardson G, Huo Y, Ahmed SM. Epithelial homeostasis. Curr. Biol. 2014 Sep 9/8/2014; 24(17): R815-25. PMID: 25202877, PMCID: PMC4196707, PII: S0960-9822(14)00785-4, DOI: 10.1016/j.cub.2014.06.068, ISSN: 1879-0445.

Huo Y, Macara IG. The Par3-like polarity protein Par3L is essential for mammary stem cell maintenance. Nat. Cell Biol [print-electronic]. 2014 Jun; 16(6): 529-37. PMID: 24859006, PMCID: PMC4083567, PII: ncb2969, DOI: 10.1038/ncb2969, ISSN: 1476-4679.

Rodriguez-Boulan E, Macara IG. Organization and execution of the epithelial polarity programme. Nat. Rev. Mol. Cell Biol. 2014 Apr; 15(4): 225-42. PMID: 24651541, PMCID: PMC4211427, PII: nrm3775, DOI: 10.1038/nrm3775, ISSN: 1471-0080.

Baschieri F, Confalonieri S, Bertalot G, Di Fiore PP, Dietmaier W, Leist M, Crespo P, Macara IG, Farhan H. Spatial control of Cdc42 signalling by a GM130-RasGRF complex regulates polarity and tumorigenesis. Nat Commun. 2014; 5: 4839. PMID: 25208761, PMCID: PMC4449154, PII: ncomms5839, DOI: 10.1038/ncomms5839, ISSN: 2041-1723.

McCaffrey LM, Macara IG. Signaling pathways in cell polarity. Cold Spring Harb Perspect Biol. 2012 Jun; 4(6): PMID: 22553378, PMCID: PMC3367552, PII: cshperspect.a009654, DOI: 10.1101/cshperspect.a009654, ISSN: 1943-0264.

McCaffrey LM, Montalbano J, Mihai C, Macara IG.. Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis. 2012.

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. 2012.

McCaffrey LM, Macara IG. Epithelial organization, cell polarity and tumorigenesis. Trends Cell Biol [print-electronic]. 2011 Dec; 21(12): 727-35. PMID: 21782440, PII: S0962-8924(11)00126-7, DOI: 10.1016/j.tcb.2011.06.005, ISSN: 1879-3088.

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. 2011 Aug 8/1/2011; 25(15): 1641-53. PMID: 21828273, PMCID: PMC3182019, PII: 25/15/1641, DOI: 10.1101/gad.2025611, ISSN: 1549-5477.

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 [print-electronic]. 2010 Oct 10/26/2010; 20(20): 1809-18. PMID: 20933426, PMCID: PMC2963683, PII: S0960-9822(10)01150-4, DOI: 10.1016/j.cub.2010.09.032, ISSN: 1879-0445.

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. 2010 Aug 8/26/2010; 466(7310): 1125-8. PMID: 20668449, PMCID: PMC2939154, PII: nature09343, DOI: 10.1038/nature09343, ISSN: 1476-4687.

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. 2010 May 5/17/2010; 189(4): 661-9. PMID: 20479467, PMCID: PMC2872902, PII: jcb.201002097, DOI: 10.1083/jcb.201002097, ISSN: 1540-8140.

McCaffrey LM, Macara IG. The Par3/aPKC interaction is essential for end bud remodeling and progenitor differentiation during mammary gland morphogenesis. Genes Dev. 2009 Jun 6/15/2009; 23(12): 1450-60. PMID: 19528321, PMCID: PMC2701573, PII: 23/12/1450, DOI: 10.1101/gad.1795909, ISSN: 1549-5477.

Macara IG, Mili S. Polarity and differential inheritance--universal attributes of life?. Cell. 2008 Nov 11/28/2008; 135(5): 801-12. PMID: 19041746, PMCID: PMC2844324, PII: S0092-8674(08)01392-5, DOI: 10.1016/j.cell.2008.11.006, ISSN: 1097-4172.

Hao Y, Macara IG. Regulation of chromatin binding by a conformational switch in the tail of the Ran exchange factor RCC1. J. Cell Biol [print-electronic]. 2008 Sep 9/8/2008; 182(5): 827-36. PMID: 18762580, PMCID: PMC2528582, PII: jcb.200803110, DOI: 10.1083/jcb.200803110, ISSN: 1540-8140.

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. 2008 Sep 9/5/2008; 31(5): 722-36. PMID: 18775331, PMCID: PMC2654589, PII: S1097-2765(08)00573-X, DOI: 10.1016/j.molcel.2008.06.025, ISSN: 1097-4164.

Mili S, Moissoglu K, Macara IG. Genome-wide screen reveals APC-associated RNAs enriched in cell protrusions. Nature. 2008 May 5/1/2008; 453(7191): 115-9. PMID: 18451862, PMCID: PMC2782773, PII: nature06888, DOI: 10.1038/nature06888, ISSN: 1476-4687.

Zhang H, Macara IG. The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase. Dev. Cell. 2008 Feb; 14(2): 216-26. PMID: 18267090, PMCID: PMC2768076, PII: S1534-5807(07)00476-5, DOI: 10.1016/j.devcel.2007.11.020, ISSN: 1534-5807.

Goldstein B, Macara IG. The PAR proteins: fundamental players in animal cell polarization. Dev. Cell. 2007 Nov; 13(5): 609-22. PMID: 17981131, PMCID: PMC2964935, PII: S1534-5807(07)00385-1, DOI: 10.1016/j.devcel.2007.10.007, ISSN: 1534-5807.

Available Postdoctoral Position Details
Posted: 6/16/2015
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.