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OFFICE LOCATIONS
DESCRIPTION OF INTERESTS
Research efforts in my laboratory are focused both in Immunology and in Bacterial Pathogenesis, two diverse fields of biomedical research for which I have two separate research groups. Projects in both fields are available for graduate students and post-doctoral fellows.
CELLULAR AND MOLECULAR REGULATION OF MUCOSAL IMMUNE RESPONSES. A major focus of my laboratory is to investigate the cellular and molecular events which modulate mucosal immune responses. We have demonstrated that LT-IIa and LT-IIb, two Type II heat-labile enterotoxins of Escherichia coli, are potent oral and nasal immunogens that have the capacity for augmenting humoral and cellular immune responses (See Figure below). Using a variety of immunological and cellular techniques (including flow cytometry, FRET fluorescent detection, cytokine multiplex analysis, mutagenesis, and the use of transgenic mice), we are evaluating the manners in which these two immunomodulators productively interact with various lymphoid cells such as T cells, B cells, and dendritic cells to induce or suppress cytokine production, co-stimulatory ligand expression, and proliferation. A practical outgrowth of these experiments is the potential to engineer novel recombinant vaccines by genetically fusing antigens from different
pathogens to the immunomodulatory enterotoxins. We have shown that upon nasal immunization, these genetically-fused proteins elicit protective immune responses in animal challenge models. Other fusion proteins being produced are incorporating antigens from Haemophilus influenzae, hepatitis virus, and tuberculosis in an effort to produce new and effective vaccines.
MOLECULAR GENETICS OF IRON ACQUISITION IN THE BORDETELLAE. a second focus of my laboratory is to investigate the mechanisms by which Bordetella pertussis, B. bronchiseptica, and B. avium, three gram-negative bacteria that infect the upper respiratory tract of children and domesticated animals, acquire essential nutrients required to colonize the respiratory tract and to sustain progressive infections. Iron (Fe) is one of the most important nutrients required by most, if not all infectious bacteria which must be obtained from the tissues and fluids of the infected host. Using proteomic, recombinant, immunological, and biochemical methods, we are unraveling the genetic and molecular components of these bacteria that mediate acquisition of Fe from host-derived heme, myoglobin, and hemoglobin. We have identified a cluster of genes (bhuRSTUV) which encodes five proteins required for uptake of heme and a second gene cluster (rhuIR) which encodes for two heme-dependent regulatory proteins which control
heme-dependent expression of the uptake systems (See Figure below). Our current research is focused on analysis of these seven genes and expressed proteins.
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SPECIALTIES
Allergy and Immunology
Infectious Disease
Medical Microbiology
Microbiology
Genomics and proteomics
Immunology
Microbial Pathogenesis
Molecular and Cellular Biology
Molecular basis of disease and Parasitology
Molecular genetics
Regulation of gene expression
Signal Transduction |
EDUCATION
| 1989 |
Doctor of Philosophy, University of North Carolina, Chapel Hill
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| 1981 |
Master of Science, University of Alabama
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| 1977 |
Bachelor of Science, University of Alabama
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EXPERTISE
Bacterial Genetics
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Bacterial Pathogenesis
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Mucosal Immunology
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PUBLICATIONS
| Connell TD; Cholera toxin, LT-I, LT-IIa and LT-IIb: the critical role of ganglioside binding in immunomodulation by type I and type II heat-labile enterotoxins.; Expert Rev Vaccines; 2007 Oct; 6(5); 821-834 |
| Mocny JC, Olson JS, Connell TD; Passively released heme from hemoglobin and myoglobin is a potential source of nutrient iron for Bordetella bronchiseptica.; Infect Immun; 2007 Oct; 75(10); 4857-4866 |
| King-Lyons ND, Smith KF, Connell TD; Expression of hurP, a gene encoding a prospective site 2 protease, is essential for heme-dependent induction of bhuR in Bordetella bronchiseptica.; J Bacteriol; 2007 Sep; 189(17); 6266-6275 |
| Liang S, Wang M, Triantafilou K, Triantafilou M, Nawar HF, Russell MW, Connell TD, Hajishengallis G; The A subunit of type IIb enterotoxin (LT-IIb) suppresses the proinflammatory potential of the B subunit and its ability to recruit and interact with TLR2.; J Immunol; 2007 Apr; 178(8); 4811-4819 |
| Liang S, Wang M, Tapping RI, Stepensky V, Nawar HF, Triantafilou M, Triantafilou K, Connell TD, Hajishengallis G; Ganglioside GD1a is an essential coreceptor for Toll-like receptor 2 signaling in response to the B subunit of type IIb enterotoxin.; J Biol Chem; 2007 Mar; 282(10); 7532-7542 |
| Arce S, Nawar HF, Muehlinghaus G, Russell MW, Connell TD; In vitro induction of immunoglobulin A (IgA)- and IgM-secreting plasma blasts by cholera toxin depends on T-cell help and is mediated by CD154 up-regulation and inhibition of gamma interferon synthesis.; Infect Immun; 2007 Mar; 75(3); 1413-1423 |
| Nawar HF, Arce S, Russell MW, Connell TD; Mutants of type II heat-labile enterotoxin LT-IIa with altered ganglioside-binding activities and diminished toxicity are potent mucosal adjuvants.; Infect Immun; 2007 Feb; 75(2); 621-633 |
| Connell TD; Cholera toxin, LT-I, LT-IIa, and LT-IIb: the critical role of ganglioside-binding in immunomodulation by Type I and Type II heat-labile enterotoxins; Expert Review of Vaccines; 2007; 6; 821-834 |
| Mocny, J., Olson, J., Connell TD; The role of spontaneous loss of heme from hemoglobin and myoglobin in iron acquisition by Bordetella bronchiseptica; Infection & Immunity; 2007; 75; 4857-4866 |
| Sebaihia M, Preston A, Maskell DJ, Kuzmiak H, Connell TD, King ND, Orndorff PE, Miyamoto DM, Thomson NR, Harris D, Goble A, Lord A, Murphy L, Quail MA, Rutter S, Squares R, Squares S, Woodward J, Parkhill J, Temple LM; Comparison of the genome sequence of the poultry pathogen Bordetella avium with those of B. bronchiseptica, B. pertussis, and B. parapertussis reveals extensive diversity in surface structures associated with host interaction.; J Bacteriol; 2006 Aug; 188(16); 6002-6015 |
| Hajishengallis G, Arce S, Gockel CM, Connell TD, Russell MW; Immunomodulation with enterotoxins for the generation of secretory immunity
or tolerance: applications for oral infections.; J Dent Res; 2005 Dec; 84(12); 1104-1116 |
| van Ginkel FW, Jackson RJ, Yoshino N, Hagiwara Y, Metzger DJ, Connell TD, Vu HL, Martin M, Fujihashi K, McGhee JR; Enterotoxin-based mucosal adjuvants alter antigen trafficking and induce inflammatory responses in the nasal tract.; Infect Immun; 2005 Oct; 73(10); 6892-6902 |
| Arce S, Nawar HF, Russell MW, Connell TD; Differential binding of Escherichia coli enterotoxins LT-IIa and LT-IIb and
of cholera toxin elicits differences in apoptosis, proliferation, and activation of lymphoid cells.; Infect Immun; 2005 May; 73(5); 2718-2727 |
| Nawar HF, Arce S, Russell MW, Connell TD; Mucosal adjuvant properties of mutant LT-IIa and LT-IIb enterotoxins that exhibit
altered ganglioside-binding activities.; Infect Immun; 2005 Mar; 73(3); 1330-1342 |
| Hajishengallis G, Tapping RI, Martin MH, Nawar H, Lyle EA, Russell MW, Connell TD; Toll-like receptor 2 mediates cellular activation by the B subunits of type
II heat-labile enterotoxins.; Infect Immun; 2005 Mar; 73(3); 1343-1349 |
| King ND, Kirby AE, Connell TD; Transcriptional control of the rhuIR-bhuRSTUV heme acquisition locus in Bordetella
avium.; Infect Immun; 2005 Mar; 73(3); 1613-1624 |
| Hajishengallis G, Nawar H, Tapping RI, Russell MW, Connell TD; The Type II heat-labile enterotoxins LT-IIa and LT-IIb and their respective
B pentamers differentially induce and regulate cytokine production in human monocytic cells.; Infect Immun; 2004 Nov; 72(11); 6351-6358 |
| Kirby A E, Connell T D; RhuR, an extracytoplasmic function (ECF) sigma factor activator, is essential for heme-dependent expression of the outer membrane heme and hemoprotein receptor of Bordetella avium; Infection and Immunity; 2004 Feb; |
| Kirby AE, King ND, Connell TD; RhuR, an extracytoplasmic function sigma factor activator, is essential for
heme-dependent expression of the outer membrane heme and hemoprotein receptor of Bordetella avium.; Infect Immun; 2004 Feb; 72(2); 896-907 |
| Murphy ER, Sacco RE, Dickenson A, Metzger DJ, Hu Y, Orndorff PE, Connell TD; BhuR, a virulence-associated outer membrane protein of Bordetella avium, is required for the acquisition of iron from heme and hemoproteins.; Infect Immun; 2002 Oct; 70(10); 5390-5403 |
| Folster JP, Connell TD; The extracellular transport signal of the Vibrio cholerae endochitinase (ChiA) is a structural motif located between amino acids 75 and 555.; J Bacteriol; 2002 Apr; 184(8); 2225-2234 |
| Drahushuk K, Connell TD, Higgins D; Pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide inhibit dendritic growth in cultured sympathetic neurons.; J Neurosci; 2002; 22; 6560-6569 |
| Kirby AE, Metzger DJ, Murphy ER, Connell TD; Heme Utilization in Bordetella avium Is Regulated by RhuI, a Heme-Responsive Extracytoplasmic Function Sigma Factor.; Infect Immun; 2001 Nov; 69(11); 6951-6961 |
| Martin M, Metzger DJ, Michalek SM, Terry Connell, 0F70L4CU7W; Distinct cytokine regulation by cholera toxin and type II heat-labile toxins involves differential regulation of CD40 ligand on CD4(+) t cells.; Infect Immun; 2001 Jul; 69(7); 4486-4492 |
| Martin, M.H., Metzger, D.J., Michalek, S.M., Terry Connell, Michael Russell; Distinct cytokine regulation by cholera toxin and the type II heat-labile enterotoxins involves differential regulation of CD40 ligand on CD4 T cells; Infect. Immun.; 2001 Jan; 69; 4486-4492 |
| Martin M, Hajishengallis G, Metzger DJ, Michalek SM, Terry Connell, Russell MW; Recombinant antigen-enterotoxin A2/B chimeric mucosal immunogens differentially enhance antibody responses and B7-dependent costimulation of CD4(+) T cells.; Infect Immun; 2001 Jan; 69(1); 252-261 |
| Martin, M., Hajishengallils, G., Metzger, D.J., Michalek, S.M., Terry Connell, Michael Russell; Recombinant antigen-entertoxin A2/B chimeric mucosal immunogens differentially enhance antibody responses and B7-dependent costimulation of T cells; Infect. Immun.; 2001 Jan; 69; 252-261 |
| Kirby, A.E., Metzger, D.J., Murphy, E.M., Connell TD; RhuI, an extracytoplasmic function sigma factor, regulates heme utilization in Bordetella avium; Infection & Immunity; 2001; 69; 6951-6961 |
| Ali A, Johnson JA, Franco AA, Metzger DJ, Terry Connell, Morris JG, Sozhamannan S; Mutations in the extracellular protein secretion pathway genes (eps) interfere with rugose polysaccharide production in and motility of Vibrio cholerae.; Infect Immun; 2000 Apr; 68(4); 1967-1974 |
| Martin M, Metzger DJ, Michalek SM, Terry Connell, Russell MW; Comparative analysis of the mucosal adjuvanticity of the type II heat-labile enterotoxins LT-IIa and LT-IIb.; Infect Immun; 2000 Jan; 68(1); 281-287 |
| Martin, M.H., Metzger, D.J., Michalek, S.M., Terry Connell, Michael Russell; Comparative analysis of the mucosal adjuvanticity of the type II heat-labile enterotoxins, LT-IIa and LT-IIb; Infect. Immun.; 2000 Jan; 68; 281-287 |
| Martin, M., Hajishengallis, G., Metzger, D., Terry Connell, Michalek, S.M., Michael Russell; Immunostimulatory activity of CT- and LT-IIa-based chimeric proteins; J. Dent. Res.; 2000 Jan; |
| Murphy ER, Dickenson A, Militello KT, Terry Connell; Genetic characterization of wild-type and mutant fur genes of Bordetella avium.; Infect Immun; 1999 Jun; 67(6); 3160-3165 |
| Michael Russell, Wu, H.-Y., Hajishengallis, G., Martin, M.H., Michalek, S.M., Hollingshead, S.K., Terry Connell, Metzger, D.; Mucosal vaccines based on cholera toxin B subunit; Immunol. Lett.; 1999 Jan; 69; 153 |
| Terry Connell, Metzger DJ, Lynch J, Folster JP; Endochitinase is transported to the extracellular milieu by the eps-encoded general secretory pathway of Vibrio cholerae.; J Bacteriol; 1998 Nov; 180(21); 5591-5600 |
| Terry Connell, Dickenson A, Martone AJ, Militello KT, Filiatraut MJ, Hayman ML, Pitula J; Iron starvation of Bordetella avium stimulates expression of five outer membrane proteins and regulates a gene involved in acquiring iron from serum.; Infect Immun; 1998 Aug; 66(8); 3597-3605 |
| Terry Connell, Metzger D, Sfintescu C, Evans RT; Immunostimulatory activity of LT-IIa, a type II heat-labile enterotoxin of Escherichia coli.; Immunol Lett; 1998 Jun; 62(2); 117-120 |
| Martin, M., Hajishengallis, G., Michael Russell, Metzger, D., Terry Connell, Michalek, S.M.; Purification of the recombinant protein SBR-LT-IIa2/B; J. Dent. Res.; 1998 Jan; 77(A); 216 |
| van den Akker F, Sarfaty S, Twiddy EM, Terry Connell, Holmes RK, Hol WG; Crystal structure of a new heat-labile enterotoxin, LT-IIb.; Structure; 1996 Jun; 4(6); 665-678 |
| Terry Connell, Metzger DJ, Wang M, Jobling MG, Holmes RK; Initial studies of the structural signal for extracellular transport of cholera toxin and other proteins recognized by Vibrio cholerae.; Infect Immun; 1995 Oct; 63(10); 4091-4098 |
| Terry Connell, Holmes RK; Mutational analysis of the ganglioside-binding activity of the type II Escherichia coli heat-labile enterotoxin LT-IIb.; Mol Microbiol; 1995 Apr; 16(1); 21-31 |
| Terry Connell, Martone AJ, Holmes RK; A new mobilizable cosmid vector for use in Vibrio cholerae and other gram-negative bacteria.; Gene; 1995 Feb; 153(1); 85-87 |
| Connell TD, Holmes RK; Characterization of hybrid toxins produced in Escherichia coli by assembly of A and B polypeptides from type I and type II heat-labile enterotoxins.; Infect Immun; 1992 Apr; 60(4); 1653-1661 |
| Connell TD, Holmes RK; Molecular genetic analysis of ganglioside GD1b-binding activity of Escherichia coli type IIa heat-labile enterotoxin by use of random and site-directed mutagenesis.; Infect Immun; 1992 Jan; 60(1); 63-70 |
| Connell TD, Shaffer D, Cannon JG; Characterization of the repertoire of hypervariable regions in the Protein II (opa) gene family of Neisseria gonorrhoeae.; Mol Microbiol; 1990 Mar; 4(3); 439-449 |
| Jobling, M.G., Terry Connell, Holmes, R. K.; Molecular genetic analysis of binding activity of B subunits of enterotoxins of the Vibrio cholerae/Escherichia coli family; The 26th Joint Conference US-Japan Cooperative Medical Science Program; 1990 Jan; |
| Murphy GL, Connell TD, Barritt DS, Koomey M, Cannon JG; Phase variation of gonococcal protein II: regulation of gene expression by slipped-strand mispairing of a repetitive DNA sequence.; Cell; 1989 Feb; 56(4); 539-547 |
| Connell TD, Black WJ, Kawula TH, Barritt DS, Dempsey JA, Kverneland K, Stephenson A, Schepart BS, Murphy GL, Cannon JG; Recombination among protein II genes of Neisseria gonorrhoeae generates new coding sequences and increases structural variability in the protein II family.; Mol Microbiol; 1988 Mar; 2(2); 227-236 |
| Terry Connell, Barritt, D.S., Black, W.J., Kawula, T. H., Klapper, D.G., Schwalbe, R.S., Stephenson, A., Cannon, J.G.; Genetic and biochemical analyses of protein II; Gonococci and meningococci; 1988 Jan; |
| Woods JP, Black JR, Barritt DS, Connell TD, Cannon JG; Resistance to meningococcemia apparently conferred by anti-H.8 monoclonal antibody is due to contaminating endotoxin and not to specific immunoprotection.; Infect Immun; 1987 Aug; 55(8); 1927-1928 |
| Connell TD, Barritt DS, Black WJ, Kawula TH, Klapper DG, Schwalbe RS, Stephenson A, Cannon JG; Genetic and biochemical analyses of protein II.; Antonie Van Leeuwenhoek; 1987; 53(6); 421-424 |
| Woods JP, Aho EL, Barritt DS, Black JR, Connell TD, Kawula TH, Spinola SM, Cannon JG; The H8 antigen of pathogenic Neisseriae.; Antonie Van Leeuwenhoek; 1987; 53(6); 533-536 |
| Terry Connell; A new technique for the surface sterilization of insect eggs.; J. Kansas Entomology Society; 1981 Jan; 54; 124-128 |
| Terry Connell; The feeding ecology of the shore fly Scatella picea (Walker)(Diptera:Ephydridae); Canadian J. Zoology; 1981; 59; 1831-1835 |
| Scheiring, J.F., Terry Connell; A description of the egg of Zeros flavipes (Cresson); J. Kansas Entomology Society; 1979; 52; 609-612 |
GRANTS
August 2006 to July 2011
Type II enterotoxins as mucosal immunomodulators
National Institutes of Health
Terry Connell, Michael Russell
$1,150,000
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December 2005 to November 2010
Oral Immunity and Adjuvant Receptors
National Institute of Dental and Craniofacial Research
Terry Connell
$420,300
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January 2004 to December 2008
Antigens of Streptococcus mutans in caries immunity
National Institute of Dental and Craniofacial Research
Terry Connell
$936,812
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December 2001 to March 2007
Type II enterotoxins as immunomodulators
National Institute for Dental & Craniofacial Research
Terry Connell
$487,051
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April 2001
NIH
Terry Connell
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April 2001 to March 2006
Type II enterotoxins as mucosal immunomodulators
National Institute for Dental & Craniofacial Research
Terry Connell
$867,000
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January 2000 to January 2001
Crystallographic investigation of the Vibrio cholerae chitinase: Structural resolution of a bacterial extracellular transport signal
State University of New York at Buffalo
Terry Connell
$20,000
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January 1995 to January 1997
A Recombinant Porphyromonas gingivalis vaccine
National Institute for Dental & Craniofacial Research
Terry Connell
$50,000
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January 1994 to January 1999
Lucille P. Markey Trust
Agency for Toxic Substances and Disease Registry, CDC
Terry Connell
$1,000,000
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January 1993 to January 1996
Extracellular secretion in Vibrio cholerae
State University of New York at Buffalo
Terry Connell
$75,000
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January 1991 to January 1996
"Training Program in Periodontal Disease", NIDR
National Institute for Dental & Craniofacial Research
Terry Connell, Norman Mohl
$1,665,033
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