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Researchers at UCD

researcher

Hilary McMahon

School of Biomolecular & Biomedical Science
Room 141, Science Centre west
University College Dublin
Belfield, Dublin 4, Ireland

Tel: +353 1 7162196
Email: hilary.mcmahon@ucd.ie

Biography

After obtaining a first class honours B.Sc. degree from University College Dublin Dr. McMahon undertook a PhD in the area of protein biochemistry and was conferred with the degree of PhD from UCD in 1998.  

Dr. McMahon's work in Prion diseases commenced in 1999 as a research associate (Jan 1999 to October 2000) at the IGH du CNRS, Montpellier, France. She returned to UCD as a college lecturer in October 2000 and was appointed to the faculty of Science in October 2002, and became a tenured academic staff member.

The group of Dr. McMahon has identified a number of new potential antiprion therapeutics including the cyclodextrins and new amphotericin derivatives.  Her group has also recently identified new potential  cellular sites that could be targeted for the development of treatments for  prion disorders and other disorders that we know are controlled by these sites. She  identified a novel link between  Prion diseases and Alzheimer's disease through the neuronal adaptor protein, X11alpha. For more information on most recent advances in prion diseases and the links between prion diseases and Alzheimer's disease see the research section. 

Dr. McMahon's research group currently studies:

The biochemical mechanisms behind Prion diseases

Therapeutic approaches to treat these disorders

The link between Prion disorders and Alzheimer's disease   
 
Research Links: SBBS Research  |  Biotechnology & Synthetic Biology Research in SBBS  |  Mechanisms of Disease Research in SBBS  |  Infection Biology Research in SBBS 

Prion, scrapie, Alzheimer's, amyloid, Hilary McMahon, aging, oxidative, Drug, UCD, Conway

Professional

Honours and Awards

Year: 2001.
Title: Presidents Research Award

Associations

Association: Biochemical society, Function/Role: Member
Association: Neuroscience Ireland, Function/Role: Member
Association: American Society for Microbiology, Function/Role: *
 

Disclosures

Invention relates to novel proteases for degrading proteinaceous infectious agents (prions): UK Patent Application No. 1522814.1 . Inventor(s):Regina O'Sullivan, Ana E. Herrero and Hilary E.M McMahon, Submitted: 23-DEC-15
Sequence of a novel protease, protease 10, for restricting the spread of prion relating diseases. Inventor(s):Ana E. Herrero and Hilary E.M McMahon, Submitted: 02-NOV-15
Sequence of a novel protease for restricting the spread of prion relating diseases. Inventor(s):Regina O'Sullivan, Ana E. Herrero and Hilary E.M McMahon, Submitted: 18-SEP-15
Compositions for treating prion disease. Filed at the European Patent Office on May 29th 2007. Application no. PCT/EP2007/004727.. Inventor(s):M.Prior and HEM McMahon, Submitted: 29-MAY-07
Antiprion action of new cyclodextrins analogues. Inventor(s):McEvoy K and McMahon HEM, Submitted: 22-APR-09
A protease, Filed at the European Patent Office, application number 10394016.9. Inventor(s):McMahon HEM, Submitted: 03-SEP-10
 

Conference Contributions

O'Sullivan J., Murphy M and McMahon H.E.M; (2010) Characteristics of a new microbial protease that degrades the prion protein. [Poster Presentation], PRION 2010 - Salzburg, Salzburg, Austria , 08-SEP-10 - 11-SEP-10.
O'SullivanJ, Comerford E.J and McMahon H.E.M.; (2010) The effect of the prion protein on Superoxiode Dismutase Activity. [Poster Presentation], Neuroscience Ireland 2010, Dublin , 02-SEP-10 - 03-SEP-10.
Soler L and McMahon H.E.M.; (2009) Antiprion activity of amphotericin analogues. [Poster Presentation], III international symposium on "The new prion biology: Basic Science, Diagnosis and Therapy", Venice, Italy , 02-APR-09 - 04-APR-09.
McEvoy, K, and McMahon, H.E.M.; (2008) Cyclodextrins working in prion disorders. [Poster Presentation], Science Foundation Ireland summit, Kilkenny, Ireland , 17-NOV-08 - 18-NOV-08.
Molloy, B. and McMahon, H.E.M.; (2008) Cholesterol and Prion disorders. [Poster Presentation], Prion Conference Madrid 2008, Madrid , 08-OCT-08 - 10-OCT-08.
McEvoy, K, and McMahon, H.E.M.; (2008) Cyclodextrins and Prion disorders. [Poster Presentation], Prion conference Madrid 2008, Madrid , 08-OCT-08 - 10-OCT-08.
Prior, M. and McMahon, H.E.M; (2007) Cyclodextrins inhibit replication of scrapie prion protein in cell culture. [Poster Presentation], Science Foundation Ireland summit, Dublin , 26-NOV-07 - 26-NOV-07.
Molloy, B. and McMahon, H.E.M. ; (2007) Cholesterol and Prion Diseases. [Poster Presentation], Annual meeting of the Irish neuroscience group.     , Tullamore , 23-NOV-07 - 24-NOV-07.
McEvoy, K, and McMahon, H.E.M. ; (2007) Investigating the action of Cyclodextrins in Prion Disorders. [Poster Presentation], Annual meeting of the Irish neuroscience group, Tullamore , 23-NOV-07 - 24-NOV-07.
Soler L and McMahon HEM; (2005) Mutant prion protein expressed in N2a cultured cells aquire scrapie-like properties. [Poster Presentation], Molecular mechanisms of neurodegeneration, Milan, Italy , 07-MAY-05 - 10-MAY-05.
McMahon H.E.M; (2005) The stress and the prion protein. [Oral Presentation], Departmental Seminars, Department of Microbiology University College Cork , 17-FEB-05.
Comerford E.J. and McMahon H.E.M; (2005) Superoxide Dismutase and Oxidative stress. [Poster Presentation], Third national research symposium of IRCSET, Dublin , 03-NOV-05.
Comerford EJ and McMahon HEM; (2004) The prion protein and SOD. [Poster Presentation], Second national research symposium of IRCSET, Dublin , 02-NOV-04 - 02-NOV-04.
Comerford EJ and McMahon HEM; (2003) Role of the prion protein in controlling oxidative stress. [Poster Presentation], IRCSET-first research symposium, Dublin , 07-NOV-03 - 07-NOV-03.
McMahon, H.E.M; (2001) Oxidative stress and prion diseases. [Oral Presentation], Departmental Seminars, Department of Zoology, University College Dublin, Ireland , 12-APR-01.
McMahon, H.E.M; (2001) The involvement of oxidative stress in prion diseases. [Oral Presentation], Research seminar, Department of Industrial Microbiology, University College Dublin, Ireland , 02-APR-01.
Mangé, A., Nishida, N., Milhavet, O., McMahon, H.E.M., Casanova, D. and Lehmann, S.; (1999) Effect of amphotericin B treatment on infectious and inherited cell culture models of Transmissible Spongiform Encephalopathies. [Poster Presentation], International symposium 'Characterisation and diagnosis of prion diseases in animals and man, Tübingen, Germany , 23-SEP-99 - 25-SEP-99.
McMahon, H.E.M; (1999) Role of the prion protein in copper metabolism. [Oral Presentation], European Union annual meeting on Transmissible Spongiform Encephalopathies, University College London , 02-JUL-99.
McMahon, H.E.M., Kelly, C. T. and Fogarty, W. M. ; (1998) Novel enzymes of fungal origin. [Oral Presentation], Industrial presentation, Department of Industrial Microbiology, University College Dublin, Ireland , 30-SEP-98.
McMahon, H.E.M., Kelly, C. T. and Fogarty, W. M.; (1998) Production of novel enzyme systems. [Oral Presentation], Industrial presentation, Department of Industrial Microbiology, University College Dublin, Ireland , 24-MAR-98.
McMahon, H.E.M.; (1997) he effect of growth rate on -amylase production by Streptomyces sp. IMD 2679. [Oral Presentation], 9th Science Faculty Postgraduate Research day (sponsored by Procter and Gamble), The Industrial Centre, University College Dublin, Ireland , 10-NOV-97.
McMahon, H.E.M., Kelly, C. T. and Fogarty, W. M. ; (1998) The effect of growth rate on a catabolically repressed protein. [Poster Presentation], The Society for General Microbiology, Irish Branch Symposium, Dublin City University, Ireland , 08-JAN-98 - 09-JAN-98.
McMahon, H.E.M., Kelly, C. T. and Fogarty, W. M. ; (1997) Thermoinactivation of the isoforms of the -amylase of Streptomyces sp. IMD 2679. [Poster Presentation], The Society for General Microbiology, Irish Branch 25th Anniversary Symposium, University College Dublin, Ireland , 18-SEP-97 - 19-SEP-97.
McMahon, H.E.M., Kelly, C. T. and Fogarty, W. M.; (1997) The amylolytic system of the thermophile Streptomyces sp. IMD2679. [Poster Presentation], The Society for General Microbiology, Irish Branch Symposium, University of Limerick, Ireland , 09-JAN-97 - 10-JAN-97.
*; (2002) *. [N/A], Transmissible Spongiform Encephalopathies: new perspectives for prion therapeutics, Paris , 01-DEC-02 - 03-DEC-02.

Committees

Committee : UCD College Biosafety Committee

Employment

Employer: UCD
Position: College lecturer
Employer: IGH du CNRS, Montpellier, France.
Position: Research Associate

Education

Year 1998 Institution: University College Dublin
Qualification: PhD Subject:
         

Publications

 

Book Chapters

McMahon HE (2017) 'Cell Culture Methods for Screening of Prion Therapeutics' In: Lawson VA (eds). Prions, Methods and Protocols. UK/USA: Springer. , pp.295-304 [DOI] [Details]
 

Peer Reviewed Journals

O'Sullivan J and McMahon HE (2016) 'Development of a heat mediated protein blotting method'. Analytical Biochemistry, 15 (499):66-70. [DOI] [Details]
O'Sullivan J, Comerford E, Rachidi W, Scott M, Hooper N, McMahon H (2015) 'The effects of the cellular and infectious prion protein on the neuronal adaptor protein X11a'. Biochimica et Biophysica Acta - General Subjects, 1850 (11):2213-2221. [DOI] [Details]
Molloy B, McMahon HE. (2014) 'A cell biased effect of estrogen in prion infection'. Journal of Virology, 88 (2):1342-53. [Details]
McMahon HEM (2012) 'Prion processing: a double-edged sword?'. Biochemical Society Transactions, 40 (4):735-738. [Details]
McEvoy K. and McMahon H.E.M. ; (2009) 'Antiprion action of new cyclodextrin analogues'. Biochimica et Biophysica Acta, 1790 (10):1382-1386. [DOI] [Details]
Soler L., Caffrey P. and McMahon H.E.M.; (2008) 'Effects of new amphotericin analogues on the scrapie isoform of the prion protein'. Biochimica Et Biophysica Acta, 1780 (10):1162-1167. [DOI] [Details]
Prior, M., Lehmann, S., Sy, MS., Molloy, B., McMahon, H.E.; (2007) 'Cyclodextrins inhibit replication of scrapie prion protein in cell culture'. Journal of Virology, 81 (20):11195-11207. [Details]
Rachidi, W., Riondel, J., McMahon, H.M. and Favier, A.; (2005) 'La protéine du prion et le cuivre : un lien mystérieux. Prion protein and copper: a mysterious relationship'. Pathologie Biologie, 53 (4):244-250. [Details]
Deignan, M.E., Prior, M., Stuart, L.E., Comerford, E.J., and McMahon, H.E.M. ; (2004) 'The structure function relationship for the Prion protein'. Journal of Alzheimers Disease, 6 (3):283-289. [Details]
McMahon, H.E.M; (2001) 'The notorious prion'. The Irish Scientist, (Year Book):221. [Details]
McMahon, H. E. M., Mangé, A., Nishida, N., Crémino, C., Casanova, D. and Lehmann, S.; (2001) 'Cleavage of the amino-terminus of the prion protein by reactive oxygen species'. Journal of Biological Chemistry, 276 (3):2286-2291. [Details]
Milhavet, O., McMahon, H.E.M., Rachidi, W., Nishida, N., Katamine, S., Mangé, A., Arlotto, M., Casanova, D., Riondel, J., Favier, A. and Lehmann, S.; (2000) 'Prion infection impairs the cellular response to oxidative stress. Proceedings of the National Academy of Sciences of the United States of America'. Proceedings of the National Academy of Sciences of the United States of America, 97 (25):13937-13942. [Details]
Mangé, A., Milhavet, O., McMahon, H. E. M., Casanova, D. and Lehmann, S.; (2000) 'Effect of amphotericin B on wild-type and mutated prion proteins in cultured cells: Putative mechanism of action in transmissible spongiform encephalopathies'. Journal of Neurochemistry, 74 :754-762. [Details]
Mangé, A., Nishida, N., Milhavet, O., McMahon, H. E. M., Casanova, D. and Lehmann, S.; (2000) 'Amphotericin B inhibits the generation of the scrapie isoform of the prion protein in infected cultures'. Virology, 74 :3135-3140. [Details]
McMahon, H. E. M., Kelly, C. T. and Fogarty, W. M.; (1999) 'Thermostability of three a- amylases of Streptomyces sp. IMD 2679'. Journal of Industrial Microbiology, 22 :96-99. [Details]
McMahon, H. E. M., Kelly, C. T. and Fogarty, W. M.; (1999) 'The high maltose-producing amylolytic system of Streptomyces sp. IMD 2679'. Biotechnology Letters, 21 :23-26. [Details]
McMahon, H. E. M., Kelly, C. T. and Fogarty, W. M.; (1997) 'The effect of growth rate on a-amylase production by Streptomyces sp. IMD 2679'. Applied Microbiology and Biotechnology, 48 :504-509. [Details]
                                                                                                                                           

Research

Research Interests

Prion diseases also known as Transmissible Spongiform Encephalopathies (TSEs) are a group of neurodegenerative disorders affecting animals and humans.  They are generally associated with the accumulation in the brain of an abnormal partially protease resistant isoform (PrPSc) of the normal endogenous prion protein (PrPC). The exact function of PrPC is not known, however most recent evidence indicates that this evolutionarily conserved protein has a role not only in TSEs but also in Alzheimer's disease (AD).

Dr. McMahon's group studies the biochemical basis of prion diseases, potential prion therapeutics and the link between AD and prion disorder. 

Links between the prion protein and Alzheimer's disease (AD). In AD abnormal processing of the amyloid precursor protein (APP) yielding amyloid beta (Aß) peptides is linked with the disease process. PrPC is now thought to play a role in AD because: The presence of PrPC has been shown to regulate Aß peptide production.  In the brains of TSE infected animals, where PrPC is converted to PrPSc, Aß levels are elevated. Mutant PrP associated with familial TSEs loose their ability to reduce Aß production.  This finding highlights the potential risk of developing additional complications in TSEs, and the severity of disease that could emanate from sporadic or infectious TSE in a patient with familial AD. AD diagnosis has already been made in disease cases arising from mutations resulting in expression of amino truncated PrPC.  These cases resulted from stop mutations in PRNP (the prion protein gene), which led to a form of PrPC that could not be transported to the cell surface. Adding to the link between PrPC and APP processing is the Valine/Methionine polymorphism at position 129 on PRNP, which has been identified as a risk factor in early onset AD.

 


 

 

 

 

Research Projects

Sponsor : University College Dublin (UCD)
Title : Modifying a antiprion protease.
Start Date / End Date : 24-MAY-16 / 30-JUN-17
Sponsor : Enterprise Ireland (EI)
Title : A novel enzyme for the decontamination of prion material.
Start Date / End Date : 30-MAR-16 / 30-JUN-16
Sponsor : University College Dublin (UCD)
Title : Expression of soluble oligomeric human amyloid beta protein in L. lactis
Start Date / End Date : 19-MAY-14 / 01-SEP-14
Sponsor : Health Research Board (HRB)
Title : Prevention of prion associated disorders
Start Date / End Date : 01-FEB-12 / 31-AUG-15
Sponsor : University College Dublin (UCD)
Title : M.Sc. Biotechnology research supervision
Start Date / End Date : 06-MAY-11 / 06-MAY-13
Sponsor : Science Foundation Ireland (SFI)
Title : A novel enzyme for the decontamination of the prion
Start Date / End Date : 01-JAN-11 / 30-APR-12
Sponsor : Science Foundation Ireland (SFI)
Title : Investigating a role for the neuronal adaptor protein in Prion diseases
Start Date / End Date : 25-AUG-08 / 31-OCT-11
Sponsor : Science Foundation Ireland (SFI)
Title : Cyclodextrins effect in prion disorders
Start Date / End Date : 02-JUN-08 / 22-AUG-08
Sponsor : University College Dublin (UCD)
Title : The Role of the Prion Protein in Regulating Superoxide Dismutase Activity
Start Date / End Date : 01-SEP-01 / 30-AUG-03
Sponsor : Enterprise Ireland (EI)
Title : Probing the Action of Amphotericin B in Prion Diseases
Start Date / End Date : 01-OCT-03 / 30-SEP-06
Sponsor : Irish Research Council for Science Engineering and Technology (IRCSET)
Title : Ms. Emma Comerford
Start Date / End Date : 01-OCT-02 / 30-SEP-05
Sponsor : Health Research Board (HRB)
Title : The Prion Proteins Role in the Cellular Oxidative State
Start Date / End Date : 01-JAN-03 / 31-DEC-05
Sponsor : Science Foundation Ireland (SFI)
Title : Investigating the action of cyclodextrins in prion disorders
Start Date / End Date : 01-AUG-06 / 31-JUL-09

Recent Postgraduates

  • Dr McMahon has supervised 6 PhD students  and 1 MSc student to completion