Projects:
To date, my work has focused on
utilizing different strategies to identify potential vaccine targets
for immunoprotection against spirochetes (namely Leptospira
and Brachyspira). There are thought to be over 100,000
severe human leptospirosis cases per year caused by more than 200
serovars. Serovar specificity is determined by lipopolysaccharide
and my work has focused on identifying conserved outer membrane
proteins (OMPs) that may stimulate heterologous protection. To derive
a comprehensive set of proteins to analyze as potential vaccinogens
I used modern proteomics to identify and analyze the expression
of leptospiral OMPs. The publication represented one of the first
published accounts of such a vaccine development strategy. With
Brachyspira I have utilized a genetic approach to identify OMPs
developed by David Blanco at UCLA called the blue halo assay. More
recently as part of a team I have applied the proteomics approach
to Pasteurella also isolating and identifying OMPs from organisms
growing inside the natural host. I have also started to use a technique
I call surfaceomics which involves expression analysis and affinity
capture of the subset of OMPs expressed on the bacterial cell surface.
In addition, I have experience with analyzing individual antigens
and have reported more detailed investigations of conserved OMPs
that may serve as protective antigens. I have also developed a lipoprotein
expression vector which on cloning of protein encoding sequence
results in the expression of lipidated membrane associated lipoproteins.
I have co-authored an authoritative review on the biology of spirochetal
OMPs and another on expression analysis of bacteria inside the host.
Curriculum
Vitae
Refereed
Journal Articles
Adlowitz, D.G.,
Sethi, S., Cullen, P.A., Adler, B. and Murphy, T.F. Human antibody
response to outer membrane protein G1a, a lipoprotein of Moraxella
catarrhalis. Infect Immun (Submitted) (2005). Impact factor = 3.8
Cuñé,
J., Cullen, P.A., Mazon, G., Campoy, S., Adler, B. and Barbe, J.
The Leptospira interrogans lexA gene is not autoregulated. J Bacteriol
(In press) (2005). Impact factor = 4.
Cullen, P.A.,
Xu, X., Matsunaga, J., Sanchez, Ko, A.I., Haake, D.A. and Adler,
B. The surfaceome of Leptospira. Infect Immun (In press) (2005).
Impact factor = 3.8
Boyce, J.D.*,
Cullen, P.A.*, Nguyen, V., Wilkie, I. and Adler, B. Analysis of
the Pasteurella multocida outer membrane sub-proteome and its response
to the in vivo environment of the natural host. Proteomics (In press)
(2005). Impact factor = 5.8
* These authors contributed equally to the work
Boyce, J.,
Cullen, P.A. and Adler, B. Genomic-scale analysis of bacterial gene
and protein expression in the host. Emerg Infect Dis 10: 1357-1362
(2004). Impact factor = 5.3
Cullen, P.A.,
Haake, D.A. and Adler, B. Outer membrane proteins of pathogenic
spirochetes. FEMS Microbiol Rev 28: 291-318 (2004). Impact factor
= 10.2
Trueba, G.,
Zapata, S., Madrid, K., Cullen, P.A. and Haake, D.A. Cell aggregation:
a mechanism of pathogenic Leptospira to survive in fresh water.
Int Microbiol 7: 35-40 (2004). This journal does not have an impact
factor as yet.
Cullen, P.A.,
Haake, D.A., S.J., Bulach, D.M., Zuerner, R.L. and Adler, B. LipL21
is a novel surface exposed lipoprotein of pathogenic Leptospira
species. Infect Immun 71: 2414-2421 (2003). Impact factor = 3.9
Cullen, P.A.,
Coutts, S.J., Cordwell, S.J., Bulach, D.M. and Adler, B. Characterization
of a locus encoding four paralogous lipoproteins of Brachyspira
hyodysenteriae. Microb Infect 5: 275-283 (2003). Impact factor =
3.8
Cullen, P.A.,
Cordwell, S.J., Bulach, D.M. and Adler, B. Construction and evaluation
of a plasmid vector for the expression of recombinant lipoproteins
in Escherichia coli. Plasmid 49: 18-29 (2003). Impact factor = 1.4
(The 5th most downloaded paper from Plasmid in 2003 with 409 downloads)
Cullen, P.A.,
Cordwell, S.J., Bulach, D.M., Haake, D.A. and Adler, B. Global analysis
of outer membrane proteins from Leptospira interrogans serovar Lai.
Infect Immun 70: 2311-2318 (2002). Impact factor = 3.9
Conference
Abstracts
Cullen, P.A.
(2004). Current advances and future research in Leptospira and Leptospirosis.
Proteomes and their practical applications. International Symposium
on Leptospira and Leptospirosis in the Americas, Mexico City, Mexico.
Invited speaker and session chair.
Cullen, P.A.
and Adler, B. (2004). The birth of surfaceomics. Gordon Research
Conference on the Biology of Spirochetes. Ventura, USA.
Cullen, P.A.,
Cordwell, S.J. and Adler, B. (2003). Leptospiral proteomics and
the surfaceome. The 9th Meeting of the Australasian Electrophoresis
and Proteomics Society, Melbourne, Australia. Invited speaker and
session chair.
Cullen, P.A.,
Lo, M., Bulach, D.M., Cordwell, S.J. and Adler, B. (2003). Construction
and evaluation of a plasmid vector for the expression of recombinant
lipoproteins in Escherichia coli. The 7th Australian Conference
on Molecular Analysis of Bacterial Pathogens, Jamberoo, Australia.
Cullen, P.A.,
Haake, D.A., S.J., Bulach, D.M., Zuerner, R.L. and Adler, B. (2002).
Identification and characterization of a novel leptospiral ‘mini-MOMP’.
The 3rd Meeting of the International Leptospirosis Society, Bridgetown,
Barbados.
Zuerner, R.L.,
Alt, D., Bulach, D.M., Adler, B., Cullen, P.A. and Haake, D.A. (2002).
Genomic sequence analysis of Leptospira borgpetersenii serovar Hardjo.
The 3rd Meeting of the International Leptospirosis Society, Bridgetown,
Barbados.
de la Pena
Moctezuma, A., Cullen, P.A., Bulach, D.M. and Adler, B. (2002).
pL18, a novel OMP is encoded in a locus homologous to the Type II
secretion pathway system of E. coli. The 3rd Meeting of the International
Leptospirosis Society, Bridgetown, Barbados.
Cullen, P.A.,
Cordwell, S.J., Bulach, D.M., Haake, D.A. and Adler, B. (2002).
Global analysis of outer membrane proteins from Leptospira interrogans
serovar Lai. Gordon Research Conference on the Biology of Spirochetes.
Ventura, USA.
Coutts, S.J.,
Cullen, P.A., Bulach, D.M. and Adler, B. (2002). Identification
and characterization of two membrane proteins from Brachyspira hyodysenteriae.
Gordon Research Conference on the Biology of Spirochetes. Ventura,
USA.
Cullen, P.A.,
Cordwell, S.J., Bulach, D.M., Haake, D.A. and Adler, B. (2001).
Identification of leptospiral outer membrane proteins. International
Proteomics Conference, Canberra, Australia.
Liu, H., Bulach,
D.M., Cullen, P.A. and Adler, B. (2001). Expression patterns of
leptospiral outer membrane proteins and sphingomyelinase H. The
6th Australian Conference on Molecular Analysis of Bacterial Pathogens,
Marysville, Australia.
Patents
Co-inventor
on an international patent entitled “Novel Brachyspira hyodysenteriae
vaccine”
Inventors: Aldler, B., Cullen, P.A., Coutts, S.J., Bulach, D.M.
and Segers, R.P.A.M.
Patent Number: WO2004007726
International Publication Date: 22 Jan 2004
Funding
National Health
and Medical Research Council of Australia C.J. Martin Fellowship
(NHMRC Grant ID: 334174).
Principal
Investigator: Paul A. Cullen
Duration: 2005-2008 (4 years)
Issuing Institution: National Health and Medical Research Council,
Canberra, Australia
Title: “Syphilis Vaccine Development”
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