Faculty Appointments
Chair, Department of Cell and Developmental Biology Professor of Cell and Developmental Biology
Louise B. McGavock Chair
Education
Ph.D., Biochemistry, University of Sheffield, Sheffield, United KingdomB.Sc., Biochemistry, University of Sheffield, Sheffield, United Kingdom
Office Address
465 21st Avenue South
U 3209 MRB III
Nashville, TN 37232-8240
U 3209 MRB III
Nashville, TN 37232-8240
Research Description
Epithelia form the majority of tissues in your body, and are the source of 90% of human cancers. Epithelial structures form sheets and tubes and are highly polarized. They arise from stem cells or progenitors.
Our lab is deeply interested in how epithelial cells make collective decisions and maintain homeostasis; and how these processes are disrupted in response to damage, and during cancer initiation. We use mouse mammary gland, plus human breast organoids as model epithelial systems. We develop novel transgenic mouse models, genome-wide CRISPR screens, and quantitative, single-molecule imaging modalities to address fundamental questions about epithelial function.
We have openings for students interested in cell and developmental biology, cancer biology, and biophysics/computational methods.
Our lab is deeply interested in how epithelial cells make collective decisions and maintain homeostasis; and how these processes are disrupted in response to damage, and during cancer initiation. We use mouse mammary gland, plus human breast organoids as model epithelial systems. We develop novel transgenic mouse models, genome-wide CRISPR screens, and quantitative, single-molecule imaging modalities to address fundamental questions about epithelial function.
We have openings for students interested in cell and developmental biology, cancer biology, and biophysics/computational methods.
Research Keywords
Cancer biology; cell biology; developmental biology; molecular biology; stem cell biology; stem cells; morphogenesis; cell polarity; epithelial biology; breast cancer; organoids; cell imaging; microscopy; biophysics; quantitative biology.
Publications
Pfannenstein A, Macara IG. A junction-dependent mechanism drives murine mammary cell intercalation for ductal elongation. Dev Cell [print-electronic]. 2023 Jul 7/10/2023; 58(13): 1126-1138.e4-1138.e4. PMID: 37141887, PII: S1534-5807(23)00162-4, DOI: 10.1016/j.devcel.2023.04.009, ISSN: 1878-1551.
Fort L, Gama V, Macara IG. Stem cell conversion to the cardiac lineage requires nucleotide signalling from apoptosing cells. Nat Cell Biol [print-electronic]. 2022 Apr; 24(4): 434-47. PMID: 35414019, PMCID: PMC9054036, PII: 10.1038/s41556-022-00888-x, DOI: 10.1038/s41556-022-00888-x, ISSN: 1476-4679.
Ahmed SM, Nishida-Fukuda H, Li Y, McDonald WH, Gradinaru CC, Macara IG. Exocyst dynamics during vesicle tethering and fusion. Nat Commun. 2018 Dec 12/3/2018; 9(1): 5140. PMID: 30510181, PMCID: PMC6277416, PII: 10.1038/s41467-018-07467-5, DOI: 10.1038/s41467-018-07467-5, ISSN: 2041-1723.
Andrews AM, McCartney HJ, Errington TM, D'Andrea AD, Macara IG. A senataxin-associated exonuclease SAN1 is required for resistance to DNA interstrand cross-links. Nat Commun. 2018 Jul 7/3/2018; 9(1): 2592. PMID: 29968717, PMCID: PMC6030175, PII: 10.1038/s41467-018-05008-8, DOI: 10.1038/s41467-018-05008-8, ISSN: 2041-1723.
Seldin L, Le Guelte A, Macara IG. Epithelial plasticity in the mammary gland. Curr. Opin. Cell Biol [print-electronic]. 2017 Dec; 49: 59-63. PMID: 29232628, PMCID: PMC6028232, PII: S0955-0674(17)30139-4, DOI: 10.1016/j.ceb.2017.11.012, ISSN: 1879-0410.
Ahmed SM, Macara IG. The Par3 polarity protein is an exocyst receptor essential for mammary cell survival. Nat Commun. 2017 Mar 3/30/2017; 8: 14867. PMID: 28358000, PMCID: PMC5379108, PII: ncomms14867, DOI: 10.1038/ncomms14867, ISSN: 2041-1723.
Huo Y, Su T, Cai Q, Macara IG. An In Vivo Gain-of-Function Screen Identifies the Williams-Beuren Syndrome Gene GTF2IRD1 as a Mammary Tumor Promoter. Cell Rep [print-electronic]. 2016 Jun 6/7/2016; 15(10): 2089-96. PMID: 27239038, PMCID: PMC5412078, PII: S2211-1247(16)30578-2, DOI: 10.1016/j.celrep.2016.05.011, ISSN: 2211-1247.
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.
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.
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 May; 5: 4839. PMID: 25208761, PMCID: PMC4449154, PII: ncomms5839, DOI: 10.1038/ncomms5839, ISSN: 2041-1723.
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.
McCaffrey LM, Montalbano J, Mihai C, Macara IG.. Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis. Cancer Cell. 2012 Nov; 22: 601-14.
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, 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.
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.
Fort L, Gama V, Macara IG. Stem cell conversion to the cardiac lineage requires nucleotide signalling from apoptosing cells. Nat Cell Biol [print-electronic]. 2022 Apr; 24(4): 434-47. PMID: 35414019, PMCID: PMC9054036, PII: 10.1038/s41556-022-00888-x, DOI: 10.1038/s41556-022-00888-x, ISSN: 1476-4679.
Ahmed SM, Nishida-Fukuda H, Li Y, McDonald WH, Gradinaru CC, Macara IG. Exocyst dynamics during vesicle tethering and fusion. Nat Commun. 2018 Dec 12/3/2018; 9(1): 5140. PMID: 30510181, PMCID: PMC6277416, PII: 10.1038/s41467-018-07467-5, DOI: 10.1038/s41467-018-07467-5, ISSN: 2041-1723.
Andrews AM, McCartney HJ, Errington TM, D'Andrea AD, Macara IG. A senataxin-associated exonuclease SAN1 is required for resistance to DNA interstrand cross-links. Nat Commun. 2018 Jul 7/3/2018; 9(1): 2592. PMID: 29968717, PMCID: PMC6030175, PII: 10.1038/s41467-018-05008-8, DOI: 10.1038/s41467-018-05008-8, ISSN: 2041-1723.
Seldin L, Le Guelte A, Macara IG. Epithelial plasticity in the mammary gland. Curr. Opin. Cell Biol [print-electronic]. 2017 Dec; 49: 59-63. PMID: 29232628, PMCID: PMC6028232, PII: S0955-0674(17)30139-4, DOI: 10.1016/j.ceb.2017.11.012, ISSN: 1879-0410.
Ahmed SM, Macara IG. The Par3 polarity protein is an exocyst receptor essential for mammary cell survival. Nat Commun. 2017 Mar 3/30/2017; 8: 14867. PMID: 28358000, PMCID: PMC5379108, PII: ncomms14867, DOI: 10.1038/ncomms14867, ISSN: 2041-1723.
Huo Y, Su T, Cai Q, Macara IG. An In Vivo Gain-of-Function Screen Identifies the Williams-Beuren Syndrome Gene GTF2IRD1 as a Mammary Tumor Promoter. Cell Rep [print-electronic]. 2016 Jun 6/7/2016; 15(10): 2089-96. PMID: 27239038, PMCID: PMC5412078, PII: S2211-1247(16)30578-2, DOI: 10.1016/j.celrep.2016.05.011, ISSN: 2211-1247.
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.
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.
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 May; 5: 4839. PMID: 25208761, PMCID: PMC4449154, PII: ncomms5839, DOI: 10.1038/ncomms5839, ISSN: 2041-1723.
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.
McCaffrey LM, Montalbano J, Mihai C, Macara IG.. Loss of the Par3 polarity protein promotes breast tumorigenesis and metastasis. Cancer Cell. 2012 Nov; 22: 601-14.
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, 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.
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.
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.
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.