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Margaret McGee

Associate Professor

School Of Biomolecular & Biomed Science
Conway Institute
Belfield
Dublin 4

Tel: +353 1 7166771
Email: margaret.mcgee@ucd.ie

Biography

2007 Permanent Lecturer, University College Dublin

2006 Visiting Scientist, Comprehensive Cancer Center, UCSF
2004-2007 Temporary Lecturer, University College Dublin
2003 Fellowship, Irish Research Council for Science, Engineering & Technology
2002-2003 Post Doctoral Researcher, Trinity College Dublin
2001 PhD Trinity College Dublin
 
Research Links: SBBS Research  |  Biotechnology & Synthetic Biology Research in SBBS  |  Mechanisms of Disease Research in SBBS  |  McGee Lab Website  

Mechanisms of Disease, Cancer, Mitotic Catastrophe, Mitotic Cell death, Genome instability, Peptidyl prolyl isomerases, Cyclophilin A, Bcl-2 proteins

Professional

Honours and Awards

Year: 1998.
Title: Trinity College Postgraduate Scholarship
Year: 2003.
Title: Fellowship, Irish Research Council for Science, Engineering & Technology
         

Committees

Committee : UCD Science Promotion

Employment

Employer: University of California, San Francisco
Position: Visiting Research Scientist, Comprehensive Cancer Research Centre
Employer: UCD
Position: Career Track investigator, Conway Institute of Biomolecular & Biomedical Research
Employer: UCD
Position: Lecturer, Biochemistry Department
Employer: TCD
Position: IRCSET Research Fellow
Employer: TCD
Position: Postdoctoral Research Fellow, Biochemistry Department

Education

Year 2001 Institution: Trinity College Dublin
Qualification: PhD Subject:
Year 1996 Institution: University of Reading
Qualification: BSc Subject:
Year 1993 Institution: Dublin Institute of Technology (DIT), IRL
Qualification: Dip Applied Science Subject:
   

Outreach Activities

Chair SBBS ENGAGE Lay Seminar Committee where PhD students talk about their research to a Lay audience
School representative, UCD Science Promotion Committee
   

Publications

     

Peer Reviewed Journals

Annibali D, Whitfield JR, Favuzzi E, Jauset T, Serrano E, Cuartas I, Redondo-Campos S, Folch G, Gonzàlez-Juncà A, Sodir NM, Massó-Vallés D, Beaulieu ME, Swigart LB, Mc Gee MM, Somma MP, Nasi S, Seoane J, Evan GI, Soucek L (2014) 'Myc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis'. Nature Communications, 5 . [DOI] [Details]
Bannon JH, O'Donovan DS, Kennelly SM, Mc Gee MM. (2012) 'The peptidyl prolyl isomerase cyclophilin A localizes at the centrosome and the midbody and is required for cytokinesis'. Cell Cycle, 11 (7):1340-1353. [DOI] [Details]
Mac Fhearraigh S, Mc Gee MM (2011) 'Cyclin B1 interacts with the BH3-only protein Bim and mediates its phosphorylation by Cdk1 during mitosis'. Cell Cycle, 10 (22):3886-3896. [DOI] [Details]
Bane FT, Bannon JH, Pennington SR, Campiani G, Williams DC, Zisterer DM, Mc Gee MM,; (2009) 'The microtubule-targeting agents, PBOX-6 and paclitaxel, induce nuclear-cytoplasmic redistribution of the peptidyl prolyl isomerases, cyclophilin A and pin1, in malignant haematopoietic cells'. Journal of Pharmacology and Experimental Therapeutics, 329 :38-47. [DOI] [Details]
Bannon JH, Mc Gee MM.; (2009) 'Understanding the role of aneuploidy in tumorigenesis'. Biochemical Society Transactions, 37 ((Pt 4):):910-913. [DOI] [Details]
Bannon, JH,Fichtner, I,O'Neill, A,Pampillon, C,Sweeney, NJ,Strohfeldt, K,Watson, RW,Tacke, M,Mc Gee, MM; (2007) 'Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo'. British Journal of Cancer, 97 :1234-1241. [DOI] [Details]
McGrath, L.B., Onnis, V., Campiani, G., Zisterer, D.M., Williams, D.C., and Mc Gee, M.M.; (2006) 'Caspase-activated DNase (CAD)-independent oligonucleosomal DNA fragmentation in chronic myeloid leukaemia cells: requirement for chymotrypsin-like serine protease activity and a Mn2+-dependent acidic endonuclease'. Apoptosis, 11 (9):1473-1489. [Details]
Mc Gee, M.M., Gemma, S., Ramunno,A., Zisterer, D.M., Fattorusso, C., Catalanotti, B., Butini, S., Fiorini, I., Claudio, P., Cucco, C., Novellino, E., Nacci, V., Williams, D.C., Campiani, G. ; (2005) 'Pyrrolo[1,5]benzoxa(thia)zepines as a New Class of Potent Apoptotic Agents. Biological Studies and Identification of an Intracellular Location of their Drug Target'. J Med Chem, 48 (13):4367-4377. [Details]
Mc Gee MM, Greene LM, Ledwidge S, Campiani G, Nacci V, Lawler M, Williams DC, Zisterer DM.; (2004) 'Selective induction of apoptosis by the pyrrolo-1,5-benzoxazepine 7-[[dimethylcarbamoyl]oxy]-6-(2-naphthyl)pyrrolo-[2,1-d] (1,5)-benzoxazepine (PBOX-6) in Leukemia cells occurs via the c-Jun NH2-terminal kinase-dependent phosphorylation and inactivation of Bcl-2 and Bcl-XL'. Journal of Pharmacology and Experimental Therapeutics, 310 (3):1084-1095. [DOI] [Details]
Mc Gee, M.M., Campiani, G., Ramunno, A., Nacci, V., Lawler, M., Williams, D.C. & Zisterer, DM.; (2002) 'Activation of the c-Jun NH2 terminal kinase (JNK) signaling pathway is essential during PBOX-6-induced apoptosis in chronic myelogenous leukemia (CML) cells'. Journal of Biological Chemistry, 227 (21):18383-18389. [DOI] Link to full text [Details]
Mc Gee, M.M., Hyland, E., Campiani, G., Ramunno, A., Nacci, V. & Zisterer D.M.; (2002) 'Caspase-3 is not essential for DNA fragmentation in MCF-7 cells during apoptosis induced by the pyrrolo-1,5-benzoxazepine, PBOX-6'. Febs Letters, 515 (1-3):66-70. [Details]
Mc Gee, M.M., Campiani, G., Ramunno, A., Fattorusso, C., Nacci, V., Lawler, M., Williams, D.C. & Zisterer, D.M. ; (2001) 'Pyrrolo-1,5-benzoxazepines induce apoptosis in chronic myelogenous leukemia (CML) cells by bypassing the apoptotic suppressor bcr-abl'. Journal of Pharmacology and Experimental Therapeutics, 296 (1):31-40. [Details]
Zisterer, D.M., Mc Gee, M.M., Campiani, G., Ramunno, A., Fattorusso, C., Nacci, V., Lawler, M. & Williams, D.C. ; (2001) 'Pyrrolo-1,5-benzoxazepines: a new class of apoptotic agents'. Biochemical Society Transactions, 29 (6):704-706. [Details]
Marangolo, M., Mc Gee, M.M., Tipton, K.F., Williams, D.C. & Zisterer, D.M. ; (2001) 'Oxidative stress induces apoptosis in C6-Glioma cells: Involvement of mitogen-activated protein kinase and nuclear factor kappa B'. Neurotoxicity Res, (3):397-409. [Details]
Glasgow, GM; McGee, MM; Tarbatt, CJ; Mooney, DA; Sheahan, BJ; Atkins, GJ; ; (1998) 'The Semliki Forest virus vector induces p53-independent apoptosis'. Journal of General Virology, 79 (NA):2405-2410. [DOI] [Details]
Glasgow, G.M., Mc Gee, M.M., Sheahan, B.J. & Atkins, G.J.; (1997) 'Death mechanisms in cultured cells infected by Semliki Forest virus'. Journal of General Virology, 78 (pt 7):1559-1563. [DOI] [Details]
                                                                                                                     

Research

Research Interests

Defective chromosome segregation during mitosis is a major contributor to malignant transformation. Higher eukaryotes have developed a strategy to eliminate mitotic-incompetent cells, so called Mitotic Catastrophe. Mitotic Catastrophe is an oncosuppressive mechanism that senses mitotic failure and responds by driving a cell into an irreversible antiproliferative state of death or senescence. Failure of the Mitotic Catastrophe process allows the continued proliferation of defective cells, leading to aneuploidy thereby contributing to tumour onset. Thus, the induction of Mitotic Catastrophe constitutes an important therapeutic endpoint.  

Mitotic Catastrophe is driven by a complex, yet poorly understood, signalling cascade that involves extensive crosstalk between cell division and cell death pathways. Our lab is particularly interested in understanding the molecular signals that connect mitotic arrest and cell death and we are investigating the role of mitochondrial proteins in the cross-talk between these independent but equally important events.  

We use proteomic and biochemical technologies to identify components of the mitotic machinery that regulate mitotic cell death. We revealed that the mitotic kinases (cdk1 and plk1) provide a direct link between the mitotic and mitochondrial machinery. We have found that mitotic specific cyclin-dependent kinase 1 (Cdk1) directly phosphorylates the pro-apoptotic BH3-only Bcl-2 family member, Bim, an event that is mediated by a temporal interaction between cyclin B1 and Bim during mitosis (Mac Fhearraigh et al., 2011).  Thus, the hyperphosphorylation of Bim may be an important event that dictates cell fate following prolonged arrest. We have also found that Protein Tyrosine Phosphatase 1B (PTP1B) is a novel substrate for the sequential phosphorylation by cdk1 and plk1 during mitotic arrest and the Cdk1-Plk1-PTP1B phosphorylation signal is a key determinant of cell fate during Mitotic Catastrophe (O'Donovan et al., 2013).  

Targeting mitotic exit is also an important strategy to overcome acquired resistance to anti-mitotic agents.  Cytokinesis represents the last stage of mitosis and involves the abscission of the intercellular bridge separating two daughter cells. Centrosome proteins are implicated in cytokinesis, yet, the identity and function of key regulators are only beginning to emerge. We have recently shown that the peptidyl prolyl isomerase, cyclophilin A, is a novel centrosome protein that is essential for the timely completion of cytokinesis (Bannon et al., 2012). Thus, we have identified a druggable target whose function is indispensable for faithful cell division and we are currently investigating the potential of small molecule cyclophilin A inhibitors as novel anti-cytokinetic agents. To date, cyclophilin substrates at the centrosome and midbody remain elusive.. Recently we have identified a number of Cyclophilin A interacting proteins at the centrosome and midbody that  represent putative isomerase substrates and a better understanding of the interaction and signalling pathways involved will unveil new strategies to target mitotic exit in cancer cells. 
 

Current Team members
Kieran Brennan (IRC Fellow)
Rebecca Gorry (PhD student)
Paul Lavin (PhD student)
Karen Grimes (Research Assistant)
 
Past Team Members
Nollaig Healy (PhD) 
Sean MacFhearraigh (PhD)
John Bannon (PhD)
Darragh O'Donovan (PhD)  
Barry McCarthy (MSc)
Fiona Bane (MSc)
Maria Calmon Schneider (MSc Student)  

 

  

                                                                                                      

                         

                                          

Research Projects

Sponsor : Science Foundation Ireland (SFI)
Title : The characterisation of cyclophilin A as a novel regulator of cytokinesis
Start Date / End Date : 01-SEP-11 / 31-AUG-15
Sponsor : University College Dublin (UCD)
Title : M.Sc. Biotechnology research supervision
Start Date / End Date : 06-MAY-11 / 07-MAY-12
Sponsor : Science Foundation Ireland (SFI)
Title : Identification and characterisation of an apoptosis-specific serine protease
Start Date / End Date : 01-SEP-08 / 31-AUG-11
Sponsor : University College Dublin (UCD)
Title : Cyclophilin A; a novel tumour suppressor and candidate for synthetically lethal anti-cancer strategies
Start Date / End Date : 26-MAY-08 / 01-DEC-09
Sponsor : Science Foundation Ireland (SFI)
Title : Investigation into the role of Protein Tyrosine Phosphatase 1B during cell death
Start Date / End Date : 09-JUN-08 / 29-AUG-08
Sponsor : Science Foundation Ireland (SFI)
Title : Determination of the molecular components connecting microtubule disruption to the proteolytic cell death machinery
Start Date / End Date : 01-SEP-07 / 31-AUG-11
Sponsor : Cancer Research Ireland (CRI)
Title : Small molecule cyclophilin A inhibitors as novel anticancer therapeutics
Start Date / End Date : 01-OCT-06 / 30-SEP-09
Sponsor : UCD Faculty of Science
Title : Equipment Grant
Start Date / End Date : 01-OCT-04 / 30-SEP-05
Sponsor : Irish Research Council for Science Engineering and Technology (IRCSET)
Title : Determination of the Molecular Eents underlying caspase-independent apoptosis
Start Date / End Date : 04-OCT-04 / 03-OCT-05
Sponsor : University College Dublin (UCD)
Title : Small molecule cyclophilin A inhibitors as novel anti-cancer agents
Start Date / End Date : 01-OCT-06 / 01-JUN-07
Sponsor : Health Research Board (HRB)
Title : The role of peptidyl-prolyl isomerases during tumourigenesis
Start Date / End Date : 01-SEP-06 / 01-APR-10
Sponsor : University College Dublin (UCD)
Title : Chronic myeloid leukaemia (CML) is a clonal disorder characterised by the overexpression of the Bcr-Abi tyrosine kinase
Start Date / End Date : 01-OCT-05 / 30-SEP-06

Recent Postgraduates

  • John Bannon
  • Sean MacFhearraigh
  • Darragh O'Donovan
  • Fiona Bane

Post Doctoral Fellow

Dr Nollaig Healy

 

Teaching

Teaching Philosophy

My key beliefs about successful teaching and student learning are to motivate and encourage student desire to understand fundamental concepts and develop transferrable skills. This requires an effective communication and interpersonal relationship between student and instructor and a varied teaching approach that works to individual student strengths.
         

Collaborators

Internal Collaborators

Dr David Gomez, Systems Biology Ireland, Conway Institute, University College Dublin, Ireland
Professor Fiona Doohan, School of Biology and 
Environmental  Science, University College Dublin. 
Dr Glen Doherty, Consultant Gastroenterologist and Physician, St Vincent's University Hospital, Dublin and Senior Clinical Lecturer, School of Medicine and Medical Science, University College Dublin. 
 

External Collaborators

Dr Laura Soucek, Vall d'Hebron Institute of Oncology, Barcelona, Spain
Dr Jean-Francois Guichou, University of Montpellier, France
Dr Tony McElligott, School of Medicine, Trinity College Dublin
Prof Jacintha O'Sullivan, Department of Surgery, St James's Hospital and Trinity College Dublin
Randox Teoranta, Donegal, Ireland