| Professor David Sheehan |
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Professor David Sheehan
Associate Professor in
Biochemistry
Principal Investigator, Environmental Research Institute,
University College Cork
Contact
Information Proteomic Research Laboratory Department of
Biochemistry University College Cork Lee Maltings Prospect
Row, Mardyke, Cork
Email:
Professor David Sheehan
Tel: +353 21 490
4207 Fax: +353 21 427
4034
Education BSc (1H), 1980,
Biochemistry, UCC Ph.D, 1985, Trinity College Dublin
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| Teaching |
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I teach Introductory Biochemistry and courses at Science III and IV
level with an emphasis on Proteins (especially enzymes), their structure
and study. I also have a strong interest in biophysical methods for
studying proteins. |
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An outline of my courses and all courses taught by staff in the
Department of Biochemistry are available in UCC's Book of Modules.
My courses are all available to registered students on Blackboard.
An electronic version of my teaching portfolio is available here.
Find my textbook Physical Biochemistry: Principles and
Applications (2000; Wileys) here. The Second Edition will be published in early 2009. |
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| Additional Links |
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| I am currently a committee member of the British
Biophysical Society and supervise PhD students funded by Irish Research Council for
Science, Engineering and Technology (IRCSET) and the Higher Education Authority
(HEA). |
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| Research Interests.
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| Developments in methodologies such as protein mass
spectrometry and two-dimensional electrophoresis promise much more routine
and systematic identification of important aspects of protein structure
like post-translational modification which are often fundamental to
understanding individual protein function. My principal research
approaches which include enzymology, biophysical methods, enzyme kinetics,
protein purification, chemistry and structure equip me to participate in
this development into the near future and beyond. |
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| Current Research Projects: |
| 1. Studies on
glutathione transferases (GSTs). |
GSTs are important in removing foreign and potentially toxic
chemicals (xenobiotics) from cells by catalysing conjugation to
glutathione and play a major role in non-catalytic binding of endogenous
and xenobiotic ligands. As such they are of major pharmacological and
environmental importance.
My group has pioneered the study of these
enzymes from fungi in order to shed light on the evolution of the main GST
classes. We have now purified GSTs from a range of species and this has
revealed that fungal enzymes are structurally related to the Theta class.
Moreover, we have purified one of the largest GSTs ever isolated from the
non-Saccharomyces yeast, Yarrowia lipolytica, which is a
component of the elongation system of protein biosynthesis EF1Bγ.
A
second activity has focused on GSTs of Mytilus edulis, a popular
bioindicator organism, with a view to their potential use as indices of
exposure to chemical pollution. We have extended these investigations by
biochemically characterising mussel GSTs, assessing levels of other
antioxidant enzymes and heat shock proteins in response to pollution and
investigating natural biological variation in antioxidant enzyme levels. |
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| Related
Publications |
- Dowd, C.A., Buckley, C.M. and Sheehan,
D.
Glutathione S-transferases of the white rot fungus,
Phanerochaete chrysosporium. (1997) Biochemical
Journal. 324, 243-248 |
- Foley, V. and Sheehan, D.
Glutathione
S-transferases of the yeast Yarrowia lipolytica have unusually
large molecular mass (1998) Biochemical Journal. 333,
839-845. |
- Dowd, C. and Sheehan, D.
Variable expression of
glutathione S-transferase isoenzymes in the fungus Mucor
circinelloides. (1999) FEMS Microbiol. Lett.s 170,
13-17. |
- Sheehan, D. and Power, A.
Effects of seasonality
on xenobiotic and antioxidant defence mechanisms of bivalve molluscs.
(1999) Comparative Biochemistry and Physiology. 123, 3-9. |
- Sheehan, D., Meade, G., Foley, V. and Dowd,
C.
Structure, function and evolution of glutathione S-transferases:
Implications for the classification of non-mammalian members of an
ancient enzyme superfamily. (2001) Biochemical Journal. 360,
1-16. |
- McGoldrick, S., O’Sullivan, S.M. and Sheehan, D.
Glutathione transferase-like proteins encoded in genomes of
yeasts and fungi: Insights into evolution of a multifunctional protein
superfamily. (2005) FEMS Microbiol. Lett.s. 242, 1-12. |
- McGoldrick, S., McCarthy, T.V. and Sheehan, D.
The 110 kDa glutathione transferase of Yarrowia
lipolytica is encoded by a homologue of the TEF3 gene from
Saccharomyces cerevisiae: Cloning, expression and homology
modeling of the recombinant protein. (2005) Biochem. Biophys.
Res. Commun. 337, 1125-1132. |
- O’Sullivan, S.M., McCarthy, R., Vargo, M., Coleman, R.,
Sheehan, D. (2006) Labelling cysteines-17 (subunit 1) of rat kidney
Alpha class glutathione transferases with 2,3,5,6-tetrachloro-1, 4-benzoquinone:
Highly correlated effects on both glutathione conjugation and tryptophan-20
intrinsic fluorescence. Biochemical Pharmacology 71, 1629-1636.
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| 2. In vitro
toxicology with molluscs. |
| We successfully developed tissue culture methods suitable
for the Pacific Oyster, Crassostrea gigas. The objective of this
work is to develop in vitro toxicological tools to supplement
in vivo toxicology work with mussels. This was extended in
the VITOX project in collaboration with Dublin Institute of
Technology. |
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| Related
Publications |
- Sheehan D.
Applications of in vitro
techniques in studies of biomarkers and ecotoxicology. In In
Vitro Methods in Aquatic Toxicology (C. Mothersill and B. Austin,
eds.). (2004) Springer-Verlag pp.55-76. |
- Ní Shúilleabháin, S., Mothersill, C., Sheehan, D.,
O'Brien, N.M., O'Halloran, J., Van Pelt, F. and Davoren, M.
In
vitro cytotoxicity testing of three zinc metal salts using
established fish cell lines. (2004) Toxicology In Vitro. 18,
367-376. |
- Davoren, M., Ní Shúilleabháin, Hartl, MG.J.,S., Sheehan,
D., O'Brien, N.M., O' Halloran, J., Van Pelt, F.N.A.M. and
Mothersill, C.
Assessing the potential of fish cell lines as tools
for the cytotoxicity testing of estuarine sediment aqueous elutriates.
(2005) Toxicology in Vitro. 19 , 421-431. |
- Davoren, M., Ní Shúilleabháin, S., O' Halloran, J., Hartl, M.G.J.,
Sheehan, D., O'Brien, N.M.,Van Pelt, F.N.A.M., and
Mothersill, C.
A test battery approach for the ecotoxicological
evaluation of estuarine sediments. (2005) Ecotoxicology.
14, 741-755. |
- Ní Shúilleabháin, S., Mothersill, C., Sheehan, D.,
O'Brien, N.M., O' Halloran, J., Van Pelt, F.N.A.M., Kilemade, M. and
Davoren, M.
Cellular responses in primary epidermal cultures from
rainbow trout exposed to zinc chloride. (2006)
Ecotoxicology and
Environmental Safety. 65, 332-334.
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| 3. Proteomics
in environmental monitoring. |
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We are applying 2-D SDS PAGE to molluscs exposed to environmental chemical pollutants in field-sampled mussels, in mussels deliberately exposed to pro-oxidants and in sediment-challenged clams. A separate project involves developing 2-D SDS PAGE methods for identifying proteins especially targeted by oxidative stress. This focuses on detection of carbonylated and glutathionylated proteins as well as effects on thiol and disulphide status. Recently, in collaboration with Tyndall Natl Laboratory, we have become interested in study of redox effects of nanoparticles. |
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| Related
Publications |
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McDonagh, B. and Sheehan, D. (2008) Effects of
oxidative stress on protein thiols and disulphides in Mytilus
edulis revealed by proteomics: Actin and protein disulphide isomerase are
redox targets. Marine Environmental Research 66, 193-195.
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McDonagh, B. and Sheehan, D. (2007) Effect of oxidative stress on protein thiols in the blue mussel, Mytilus
edulis: Proteomic identification of target proteins. Proteomics, 7, 3395-3403.
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Chora, S., McDonagh, B., Sheehan, D., Starita-Geribaldi, M., Romeo, M and Bebianno, M.J. (2008) Ubiquitination and carbonylation as markers of oxidative stress in Ruditapes
decussatus. Marine Environmental Research 66, 95-97.
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Sheehan D. (2007) Potential of proteomics in environmental health. Reviews
on Environmental Health 22, 175-194.
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Prevodnik, A., Gardeström, J., Lilja, K., Elfwing, T., McDonagh B., Petrovic, N., Tedengren, M., Sheehan,
D. and Bollner, T. (2007) Oxidative stress in response to xenobiotics in the blue mussel Mytilus
edulis L: Evidence for variation along a natural salinity gradient of the Baltic Sea. Aquatic
Toxicology, 82, 63-71.
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Dowling, V.A. and Sheehan D. (2006) Proteomics as a route to identification of toxicity targets in ecotoxicology Proteomics 6, 5597-5604.
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Dowling, V., Hoarau, P., Romeo, M., O’Halloran, J., F. van Pelt, F. N. A. M., O’Brien, N.M., and Sheehan,
D. (2006) Protein carbonylation and heat shock response in Ruditapes
decussatus following p,p'-dichlorodiphenyldichloroethylene (DDE) exposure: a proteomic approach reveals DDE causes oxidative stress. Aquatic
Toxicology 77, 11-18.
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| 4. Redox Proteomics. |
| We are interested in application and development of methods for detection of lesions introduced into proteins both under conditions of oxidative stress but also during redox signalling. This now includes gel-based and gel-free methods. We are especially interested in using the spontaneously hypertensive rat as a model for study of redox lesions in kidney. |
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| Related
Publications |
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Tyther, R., Ahmeda, A., Johns, E. and Sheehan
D. (2008) Protein carbonylation in kidney medulla of the spontaneously hypertensive rat. Proteomics
Clin. Invest. IN PRESS
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Sheehan D. and McDonagh B. (2008) Bivalves and oxidative stress: A proteomics approach. Invertebrate
Survival Journal 5, 110-123.
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Tyther, R., Ahmed, M., Johns, E. and Sheehan,
D. (2007) Proteomic identification of nitrosylated proteins in hypertensive rat kidneys. Proteomics 7, 4555-4564
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Sheehan D. (2006) Detection of redox-based modification
in two dimensional electrophoresis proteomic separations. Biochemical
and Biophysical Research Communications 349 ,
455-462.
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| 5. Nanotoxicology. |
| Nanomaterials represent a major potential toxicological threat because of their ability to cross biological barriers such as the intestine, blood-brain barrier and even the cell membrane. In collaboration with Drs. Daniela Iacopino and Hugh Doyle (Tyndall National Laboratory) and Profs. Gareth Redmond and Ken Dawson (UCD) we are studying effects of nanoparticles on the redox status of a variety of biological systems. |
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| Related
Publications |
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Hu, W., Keane, C., Doyle, H., Iacopino, D., Redmond, G., and Sheehan,
D. (2008) Antioxidant effects of gold nanoparticles revealed by study of protein thiols in Escherichia
coli. Nanotoxicology SUBMITTED
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Tedesco, S., Doyle, H., Redmand, G. and Sheehan,
D. (2008) Gold nanoparticles effects on mussel Mytilus
edulis: A proteomic approach. Marine
Environmental Research 66, 131-133.
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| Current Research Grants |
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2008 €72,000 Irish Research Council for Science Engineering and Technology PhD grant Proteomics approach to oxidative stress in Daphnia
magna.
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2007 Invited participant in COST
action FA0603 Plant Proteomics in Europe .
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2006 €40,000
Environmental Protection Agency. A
novel green technology for environmental remediation of chloroaromatic
contaminants. Joint with Dr Marcel Jansen
(ZEPS, UCC).
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2006 €72,009 Irish Research Council
for Science Engineering and Technology PhD grant Redox proteomic investigation
of the mussel Mytilus edulis in ecotoxicology .
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2005 €150,000
Irish Health Research Board grant; Dental Erosion in Irish
Teenagers: An Epidemiological and Laboratory Investigation.
Collaboration with Dr Helen Whelton, Dental School, UCC.
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| Publications and Editorial Activities |
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Main author of over 70 refereed papers, over 30 other
publications and 4 books.
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- Sheehan, D. (Editor) (1997)
Bioremediation Protocols
Volume 2 in series Methods in Biotechnology
(Humana Press, series editor Prof John Walker). 339pp.
- Sheehan, D. (2000)
Physical Biochemistry: Principles and Applications
John Wiley & Sons Ltd. London . 350pp.
- Sheehan, D. (2009)
Physical Biochemistry: Principles and Applications,
John Wiley & Sons Ltd. London.
(350pp; http://www.wiley.co.uk ).
Second edition published in Spring 2009.
- Sheehan, D. (Editor) (2009)
Two Dimensional Electrophoresis Protocols,
(Humana Press, series editor Prof John Walker).
(450pp.; http://www.humanapress.com).
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Would you like to view my Full Publication List?
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For the past five years, I have acted as referee for 40 peer-reviewed
journals including:
- The Biochemical Journal;
- Biochimica et Biophysica Acta;
- Archives of Biochemistry and Biophysics;
- Environmental Pollution;
- Archives of Environmental Contamination and Toxicology;
- Science of the Total Environment;
- European Journal of Biochemistry Biotechnology and Applied
Biochemistry;
- International Journal of Biochemistry and Cell Biology;
- Environmental Toxicology and Chemistry.
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1999 - Date Editorial Advisor,
Biochemical Journal
2002 - Date Member of Editorial Board Essays in Biochemistry (Portland Press)
2006 - Date
Member of Editorial Board Research Journal of Biological Sciences (Medwell)
2008 - Date
Member of Editorial Board Drug Testing and Analysis (Wiley-Blackwell)
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| Recently reviewed grants for: Italian Ministry of
Universities; Biotechnology and Biological Sciences Research Council (UK);
Wellcome Trust (UK); Natural and Environmental Research Council (UK),
Association for International Cancer Research (UK), the Alzheimer's
Association (USA), the Alzheimer's Society (UK), the Nuffield Trust
(UK). |
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| Postgraduate Research Supervision |
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| Research Group |
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Sara Tedesco , MSc
PhD student (Irish Research Council for Science Engineering and
Technology EMBARK studentship). |
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Project Redox proteomic investigation of the mussel Mytilus
edulis in ecotoxicology
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| Publications |
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Gorbi S., Pellegrini D., Tedesco S., Regoli
F. (2004).
Antioxidant efficiency and detoxification enzymes
in spotted dogfish Scyliorhinus canicula.
Mar. Environ.
Res. 58: 293-297
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Regoli F., Gorbi S., Machella N., Tedesco S.,
Benedetti M., Bocchetti R., Notti A., Fattorini D., Piva F., Principato
G. (2005).
Pro-oxidant effects of extremely low frequency
electromagnetic fields in the land snail Helix aspersa.
Free
Radical Biology & Medicine 39: 1620-1628.
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Regoli F. , Gorbi S., Fattorini D., Tedesco S.,
Notti A., Machella N., Bocchetti R., Benedetti M., Piva F.
(2006).
Use of the Land Snail Helix aspersa as
Sentinel Organism for Monitoring Ecotoxicologic Effects of
Urban Pollution: An integrated Approach.
Environmental Health Perspectives 114: 63-69
- Tedesco, S., Doyle, H., Redmond, G. and Sheehan, D. (2007).
Gold Nanoparticles Effects on Mussel Mytilus Edulis: A Proteomic Approach.
Marine Environmental Research. IN PRESS.
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Hu Wentao, MSc
PhD student
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Project Novel selection approaches in redox proteomics
Career History
Wentao completed a B.Sc. in Material Science, SUES, Shanghai, China. He came to Ireland in 2006 to complete an MSc in Applied Science (Biotechnology).
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Louis-Charles Rainville, MSc
PhD student
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Project
Proteomics approach to oxidative stress in Daphnia magna
Career History
Louis-Charles is a Canadian student from Quebec Province. He holds a BSc in Biochemistry and Biotechnologies and a MSc in oceanography from the University of Quebec (ISMER,UQAR), during which he started specialising in ecotoxicology by exploring multixenobiotic resistance in marine algae.. He has a strong interest in proteins and biophysics, but wants to apply this mostly to the environmental field. He is a lover of science, philosophy and knowledge in general. He says, you'll generally see him in a lot of places as he tends to get involved a lot in university life! His PhD research topic is Proteomics approach to oxidative stress in Daphnia magna. |
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| Outreach Activities |
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| Our laboratory is actively involved in promoting Science at
primary and secondary school levels. We regularly accept transition year
students as part of their school work experience. We regularly host young
scientists from EU countries for short training internships in proteomics. |
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| ©2009 Department of Biochemistry, University College Cork,
Ireland. |
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