|
|
Gerald E. Duhamel, DVM, PhD
Research Interests
My long-range goal is to define basic mechanisms of host-parasite
interactions, and their relationship to susceptibility or resistance
against disease, particularly within the framework of enteric diseases.
I am engaged in basic and applied biomedical research aimed at characterizing
molecular mechanisms of microbial pathogenesis and host defense with
practical applications to diagnosis and control of enteric diseases
of animals and humans. Specifically, I am investigating the biology
of polymicrobial interactions in inflammatory bowel diseases caused
by Brachyspira pilosicoli, a newly discovered pathogenic intestinal
spirochete, Helicobacter and Campylobacter species. I am also interested
in understanding the role of heterotypic immunity in protection against
intestinal disease caused by group A rotaviruses. Current research
addresses bacterial virulence factors and model development of intestinal
injury and repair, phenotypic and genotypic bases of microbial diversity,
diagnosis of enteric diseases using nucleic acid-based and immunoassay
detection methods, and subunit and recombinant vaccine development.
Virology
Research Interest
Role of Group A Rotavirus P Protein in Induction of Heterotypic
Immunity. Despite of the availability of vaccines, group A rotaviruses
(RV) continue to be a leading cause of entritis in children and neonatal
animals worldwide. Because RVs with several G (VP7):P (VP4) variants
can infect susceptible hosts, current vaccine strategies might not
elicit protective antibodies against all potential RV challenge.
The central hypothesis of my research is that the VP5* region of
RV P protein contains epitopes that can elicit antibodies reactive
against heterologous RV types. Our studies on the functional domains
of group A RV P protein using convalescent gnotobiotic calves indicate
that infection with bovine RV with P6[1] or P8[11] serotype/genotype
specificities is accompanied with humoral IgG antibodies to at least
five cross-reactive and neutralizing linear B-cell epitopes located
within VP5* of the virus. These epitopes have potential for development
of vaccines capable of eliciting protective immunity against a broad
spectrum of RV serotypes/genotypes causing enteritis.
Most Significant Referred Journal Publications
Carvajal A, De Arriba
ML, Rodriguez H, Vidal AB, Duhamel GE, Rubio P. Brachyspira hyodysenteriae
is relatively more prevalent than B. pilosicoli among commercial
pig farms with diarrhoea in Spain. Vet Rec, in press.
Dassanayake RP, Sarath G, Duhamel GE. 2005. Penicillin-binding proteins
in the pathogenic intestinal spirochete Brachyspira pilosicoli. Antimicrob
Agents Chemother 49: in press.
Dassanayake RP, Zhou Y, Hinkley S, Stryker CJ, Plauche G, Borda
JT, Sestak K, Duhamel GE. 2005. Characterization of cytolethal distending
toxin of Campylobacter species isolated from captive macaque monkeys.
J Clin Microbiol 43:641-649.
Samrakandi MM, Zhang C, Zhang M, Nietfeldt J, Kim J, Iwen PC, Olson
ME, Fey PD, Duhamel GE, Hinrichs SH, Cirillo JD, Benson AK. 2004.
Genome diversity among regional populations of Francisella tularensis
subspecies tularensis and Francisella tularensis subspecies holartica
isolated from the U.S. FEMS Microbiol Lett 237:9-17.
De Cock HEV, Marks SL, Stacy BA, Zabka T, Burkitt J, Lu G, Steffen
DJ, Duhamel GE. 2004. Ileocolitis associated with Anaerobiospirillum
in cats. J Clin Microbiol 42:2752-2758.
Johansson KE, Duhamel GE, Bergsjö B, Engvall EO, Persson M,
Pettersson B, Fellström C. 2004. Identification of three clusters
of canine intestinal spirochaetes by biochemical and 16S rDNA sequence
analysis. J Med Microbiol 53:345-350.
Dassanayake RP, Caceres NE, Sarath G, Duhamel GE. 2004. Biochemical
properties of membrane-associated proteases of Brachyspira pilosicoli
isolated from humans with intestinal disorders. J Med Microbiol 53:319-323.
Duhamel GE, Stryker CJ, Lu G, Wong VJ Tarara RP. 2003. Colonic spirochetosis
of colony-raised rhesus macaques associated with Brachyspira and
Helicobacter. Anaerobe 9:45-55.
De Arriba ML, Vidal AB, Carvajal A, Pozo J, Martinez A., Duhamel
GE, Rubio P. 2002. First confirmation of porcine colonic spirochaetosis
caused by Brachyspira pilosicoli in Iberian pigs in Spain.Vet Rec
150:250-251.
Duhamel GE. 2001. Comparative pathology and pathogenesis of naturally
acquired and experimentally induced colonic spirochetosis. Anim Health
Res Rev 2:3-17.
Zhang P, Cheng X, Duhamel GE. 2000. Cloning and DNA sequence analysis
of an immunogenic glucose/galactose MglB lipoprotein homologue from
Brachyspira pilosicoli, the agent of colonic spirochetosis. Infect
Immun 68:4559-4565.
Klein EC, Gebhart CJ, Duhamel GE. 1999. Fatal outbreaks of proliferative
enteropathy caused by Lawsonia intracellularis in young colony-raised
rhesus macaques. J Med Primatol 28:11-18.
Duhamel GE, Trott DJ, Muniappa N, Mathiesen MR, Tarasiuk K, Lee
JI, Hampson DJ. 1998. Canine intestinal spirochetes consist of Serpulina
pilosicoli and a newly identified group provisionally designated “Serpulina
canis” sp. nov. J Clin Microbiol 36:2264-2270.
Campbell RE, Lu W, White AK, Duhamel GE. 1998. Molecular and immunologic
characterization of group A bovine rotavirus field isolates with
P8[11] spike protein. Arch Virol 143:1021-1028.
White A, Hansen-Lardy L, Brodersen B, Kelling CL, Hesse R, Duhamel
GE. 1998. Enhanced immunohistochemical detection of infectious agents
in formalin-fixed, paraffin-embedded tissues following heat-mediated
antigen retrieval. J Vet Diagn Invest 10:214-217.
Fisher LN, Mathiesen MR, Duhamel GE. 1997. Restriction fragment
length polymorphism of the periplasmic flagellar flaA1 gene of Serpulina
species. Clin Diagn Lab Immunol 4:681-686.
Muniappa N, Duhamel GE. 1997. Outer membrane-associated serine protease
of intestinal spirochetes. FEMS Microbiol Let 154:159-164.
Duhamel, GE, Elder RO, Muniappa N, Mathiesen MR, Wong VJ, Tarara
RP. 1997. Colonic spirochetal infections in nonhuman primates that
were associated with Brachyspira aalborgi, Serpulina pilosicoli,
and unclassified flagellated bacteria. Clin Infect Dis 25(Supp 2):186-188.
Fisher LN, Duhamel GE, Westerman RB, Mathiesen MR. 1997. Immunoblot
reactivity of polyclonal and monoclonal antibodies with periplasmic
flagellar FlaA1 and FlaB of porcine Serpulina species. Clin Diagn
Lab Immunol 4:400-404.
Trott DJ, Stanton TB, Jensen NS, Duhamel GE, Johnson JL, Hampson
DJ. 1996. Serpulina pilosicoli sp. nov., the agent of porcine intestinal
spirochetosis. Intl J Syst Bacteriol 46:206-215.
Lu W, Duhamel GE, Hoshino Y, Benfield DA, Nelson EA, Hesse RA. 1995.
Characterization of the bovine group A rotavirus strain neonatal
calf diarrhea virus (NCDV)-Cody. J Clin Microbiol 33:990-994.
Lu W, Duhamel GE, Benfield DA, Grotelueschen DM. 1994. Serological
and genotypic characterization of group A rotavirus reassortants
from diarrheic calves born to dams vaccinated against rotavirus.
Vet Microbiol 42:159-170.
Hesse RA, Couture LP, Ellsworth SR, Duhamel GE, Lu W, Dickinson
EO, Benfield DA. 1993. Production and characterization of VP4/VP7
reassortant swine rotaviruses derived from Gottfried and OSU parental
strains. Am J Vet Res 54:1623-1629.
Selected Chapters in Books
Hampson DJ, Duhamel GE. Porcine colonic
spirochetosis/Intestinal spirochetosis. In: Diseases of Swine.
9th ed. Straw BE, D’Allaire
S, Mengeling WL, and Taylor DJ (eds). Iowa State University Press,
Ames, Iowa, pp. pending.
Duhamel GE. 2002. Neonatal enteric disease vaccines. In: Field Guide
to Large Animal Internal Medicine. Smith BP (ed). Mosby, Inc., St.
Louis, Missouri, p. 417.
Duhamel GE. 2001. Neonatal calf enteric disease vaccines. In: Large
Animal Internal Medicine. 3rd ed., Smith BP (ed). Mosby, Inc.,
St. Louis, Missouri, pp.1423-1427.
C:Nebraska Center for Virology and Nebraska Center for Virology
1/3.5
NCV-GED03-05.wpd
|
