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Brief Biographic Sketch of Prof David Sheehan BSc PhD DSc
Head of School of Biochemistry and Cell Biology,
University College Cork, Ireland
Science
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BSc in Biochemistry, University
College Cork, 1980 (First class
Hons)
PhD Biochemistry, Trinity College
Dublin, 1985
DSc (advanced doctorate) on
published work, National
Universityof Ireland, 2009
Expert in protein biochemistry,
isolation, characterization
Glutathione transferases, heat
shock and other stressresponse
proteins
Research:
• Redox proteomics
• Ecotoxicology
111 peer-reviewed papers (h-index = 31)
4 books including Physical Biochemistry:
Principles and Applications (Wileys, 2nd
edition)
Supervised 17 PhDs and 19 MScs
External examiner (18 PhDs) Spain, UK,
Ireland, Sweden, Norway, Portugal, France
Editorial Boards: International Journal of
Proteomics, Drug Testing and Analysis,
Toxins, (Assoc. ed) Journal of Integrated –
Omics; Journal of Proteome Science and
Computational Biology; (Assoc. ed) J.
Biochem. Pharmacol. Res.
Research Interests
 Redox proteomics
 Proteins absorb most reactive oxygen species during oxidative
stress. This damages proteins and changes them covalently thus
leading to biochemical consequences. We use a redox proteomics
toolkit to explore what proteins are targeted by OS in various
situations including in diseases such as hypertension.
 Ecotoxicology
 Sentinel species can give information on the quality of their environment.
We use bivalves as bioindicators of aquatic toxicology. Our redox
proteomics toolkit reveals what biochemical processes are targeted. We are
especially interested in nanomaterials and pharmaceuticals as emerging
categories of aquatic pollutants.
Recent Publications (2014)
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Sellami, B., Louati, H., Khazri, A., Mezni A., Dellali, M., Aissa, P., Ezzeddine M., Beyrem, H., Sheehan D. (2014) Effect of Permethrin,
Anthracene and mixture exposure on shell components, enzymatic activities and protein status in the Mediterranean clams Venerupis
decussata. Aquatic Toxicology IN PRESS.
Rainville L.-C., Varela, A.C., Sheehan, D. (2014) Application of the redox-proteomics toolbox to Daphnia magna challenged with model prooxidants copper and paraquat. Environmental Toxicology and Chemistry. IN PRESS
Ilyas S., Rehman A., Coelho Varela A., Sheehan D. (2014) Redox proteomics changes in the fungal pathogen Trichosporon asahii on arsenic
exposure: Identification of protein responses to metal-induced oxidative stress in an environmentally-sampled isolate. PLoS One 9, e-102340
Trevisan, R., Delapedra, G., Mello D.F., Arl, M., Schmidt, E.C., Bouzon, Z.L., Fisher, A., Sheehan, D., Dafre, A.L. (2014) Gills are an initial
target of zinc oxide nanoparticles in oysters Crassostrea gigas, leading to mitochondrial disruption and oxidative stress. Aquatic
Toxicology,153, 27-38. (http://dx.doi.org/10.1016/j.aquatox.2014.03.018)
Cole C, Coelho AV, Sheehan D. (2014) Proteomic responses to metal-induced oxidative stress in hydrothermal vent-living mussels,
Bathymodiolus brevior, on the Southwest Indian Ocean vent. Marine Environmental Research, 96, 29-37.
Sellami, B., Khazri, A., Louati, H., Boufahja F., Dellali, M., Sheehan D., Aissa, P., Ridha Driss, M., Mahmoudi, E., Beyrem, H. (2014) Effects of
permethrin on biomarkers in the Mediterranean clam Ruditapes decussatus. Bulletin of Environmental Contamination and Toxicology. 92,
574-578.
Hu, W., Culloty, S., Darmody, G., Lynch, S., Davenport, J., Ramirez-Garcia, S., Dawson, K.A., Lynch, I., Blasco, J., Sheehan, D. (2014) Toxicity
of copper oxide nanoparticles in the blue mussel, Mytilus edulis. Chemosphere 108, 289-299.
Karlsen, O.A., Sheehan, D., Goksøyr A. (2014) Alterations in the Atlantic Cod (Gadus morhua) hepatic thiol-proteome after methylmercury
exposure, Journal of Toxicology and Environmental Health, Part A: Current Issues 77, 650-662,
Sellami, B., Mahmoudi, E., Dellali, M., Aissa, P., Coelho, A.V., Sheehan, D. (2014) Effects of permethrin exposure on antioxidant enzymes and
protein status in Mediterranean clams Ruditapes decussatus. Environmental Science and Pollution Research. 21, 4461–4472.
Rainville L.-C., Carolan D, Varela, A.C., Doyle, H., Sheehan, D. (2014) Proteomic
evaluation of citrate-coated silver nanoparticles toxicity in Daphnia magna. The Analyst 139, 1678-1686.
Allocati, N., Masulli, M., Del Boccio, P., Pieragostino, D., D’Antonio, D., Sheehan, D., Di Ilio C. (2014) Identification of an elongation factor
1Bg protein with glutathione transferase activity in both yeast and mycelial morphologies from human pathogenic Blastoschizomyces
capitatus. Folia Microbiologica 59, 107-113.
Schmidt W., Rainville L.-C., McEneff G., Sheehan D., Quinn B. (2014) A proteomic evaluation of the effects of the pharmaceuticals diclofenac
and gemfibrozil on marine mussels (Mytilus spp.). Evidence for chronic sublethal effects on stress-response proteins. Drug Testing and
Analysis. 6, 210-219.
Karmous, I., Chaoui, A., Crinelli, R., Scoccianti, V., Sheehan, D., Jaouani, K., El Ferjani, E. (2014) Role of the ubiquitin-proteasome pathway
and some peptidases during seed germination and copper stress in bean cotyledons. Plant Physiology and Biochemistry 76, 77-85.
Books
Nanoparticles
Materials in a size range, with at least one dimension
between 1-100nm. (SCENHIR 2005; Moore 2006).
Globular
Tubular
Complex
geometries
Size determined by TEM
for gold nanoparticles (~5nm)
EFFECTS OF NANOPARTICLES
 THEY CAN CROSS BIOBARRIERS
 OFTEN THEY DAMAGE ORGANELLES
 ESPECIALLY MITOCHONDRIA
 ACCUMULATE IN LYSOSOMES?
 THEY CAN BE COATED WITH PROTEINS
 THEY OFTEN TRIGGER OXIDATIVE STRESS
A New Toxicology?
 WHAT IS MEANT BY DOSE IN THIS CONTEXT?
 HOW TO CONTROL FOR LEACHING OF METALS
FROM NPs?
 HOW TO MODEL PARTITIONING?
 IN ENVIRONMENTAL COMPARTMENTS
 IN TISSUES
 IN CELLS
 RISK ASSESSMENT?
 IS ANOTHER ASBESTOS LURKING?
 WILL THE POLLUTER REALLY PAY?
THE OXYGEN PARADOX
OXYGEN IS ESSENTIAL FOR AEROBIC METABOLISM BUT
PRODUCES TOXIC REACTIVE OXYGEN SPECIES (ROS)
PHOTOSYNTHETIC
CYANOBACTERIA
ORIGIN OF
EARTH
4,500 MYA
APPEARANCE OF
MOLECULAR O2
ENDOSYMBIOSIS
3,800 MYA
REDUCED
ENVIRONMENT
OZONE (O3)
LAYER
2,500 MYA
OXIDISED
ENVIRONMENT
PRESENT
ROS ARE HIGHLY REACTIVE WITH
BIOMATERIALS
 IN MANY CASES, ROS REACTIONS ARE ONLY
LIMITED BY RATE OF DIFFUSION – THEY
REACT VERY QUICKLY
 BIOMATERIALS CAN ABSORB ROS (e.g. .HO)
•DNA (6%)
•RNA (7%)
•PROTEINS (69%)
•SMALL MOLECULES (18%)
PROTEINS ARE
THEREFORE
KEY TARGETS FOR ROS
PROTEOMICS: DISCOVERY-LED
APPROACH TO BIOMARKERS
2DE GELS CAN BE DIGITALISED
- IMAGE ANALYSIS
REDOX PROTEOMICS
 PROTEINS CAN BE COVALENTLY MODIFIED BY
ROS/RNS
O
H
N
 NITROSYLATION OF TYROSINES
CH
O
H
N
C
CH
CH2
C
CH2
 CARBONYLATION
N
OH
OH
OH
O
HN
 OXIDATION OF CYSTEINE THIOLS
O
O
C
C
CH
HN
CH
CH 2
CH 2
H2C
H2C
NH 2
C
H2
H2C
CH
Aminoadipic acid
semialdehyde
Lysine
O
O
H2C
O
C
N
N
Proline
2-Pyrrolidone
O
O
C
C
CH
NH
CH
H2C
HN
H2N
CH 2
CH 2
H2C
O
CH 2
CH
C
NH
Arginine
Glutamic
semialdehyde
NH
Thiol groups and oxidative stress
SO3H
SH
Proteins
50-75%
SO2H
SH
ROS
SH
SH
SOH
SH
or
S-S-R
SH
Carbonylation
DNPH
-O-
+
DNPH
O=
PRT
PRT
ANTI-DNP
ECL
DNPH
DNPH
-O-
-OANTI-IgG
PRT
PRT
Mussels treated with copper nanoparticles –
copper accumulates in gill as dose >s.
Gill
Mantle
Digestive
Gland
Mussels treated with copper nanoparticles –thiols are
oxidised (< IAF) and carbonylated (> FTSC)
Selection of proteins with thiol groups
- shotgun proteomics
Ctrl
GNP
CdCl2
Digestive gland protein extracts
+
Activated
thiol sepharose
DTT
@
Thiol- proteins
R-SH
R-SH
Daphnia magna exposed to CuO NPs
CONCLUSIONS
• NANOPARTICLES CAN ENTER ORGANISMS AND
CROSS BIOBARRIERS
• THEY FREQUENTLY TRIGGER OXIDATIVE STRESS
• OFTEN, CYTOSKELETAL OR STRESS-RESPONSE
PROTEINS ARE TARGETS
• GEL-BASED AND GEL-FREE PROTEOMICS OFFER
ROUTES TO TARGET IDENTIFICATION
Journal of Proteomics & Bioinformatics
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For more details on Conferences Related
Journal of Proteomics & Bioinformatics
please visit:
http://www.conferenceseries.com/bioc
hemistry-meetings
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