• Primary Faculty Profiles
• Bankert, Richard, Ph.D., V.M.D., Professor
• Bianco, Piero, Ph.D., Associate Professor
• Campagnari, Anthony, Ph.D., Professor
• Collins, Arlene, Ph.D., Associate Professor
• Connell, Terry, Ph.D., Professor
• Egilmez, Nejat, Ph.D., Associate Professor
• Hakansson, Anders, Ph.D., Assistant Professor
• Hay, John, Ph.D., Professor
• Jacobs, Amy, Ph.D., Assistant Professor
• Melendy, Thomas, Ph.D., Associate Professor
• Panepinto, John, Ph.D., Assistant Professor
• Read, Laurie, Ph.D., Professor
• Russell, Michael, Ph.D., Professor
• Ruyechan, William, Ph.D., Professor and Chairman
• Thacore, Harshad, Ph.D., Associate Professor
• Williams, Noreen, Ph.D., Professor
• Adjunct Faculty Profiles
• Departmental Publications
• Career Opportunities
• The Witebsky Center
• Seminars

Faculty and Research

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Education:

1989, Ph.D., University of North Carolina, Chapel Hill, NY
1981, M.S., University of Alabama, University, AL
1977, B.S., University of Alabama, University, AL

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Research Interests:

Research efforts in my laboratory are focused both in Immunology and 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.      
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 adjuvants which augment humoral and cellular immune responses to foreign antigens (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 mechanisms in which these two immunomodulators productively interact with various immunocompetent cells (T cells, B cells, dendritic cells, macrophages) to induce or suppress cytokine production, co-stimulatory ligand expression, and proliferation.  Recent experiments have implicated a role for Toll-like receptors (TLR) in some of the immunomodulatory activities of LT-IIa and LT-IIb.  A practical outgrowth of these experiments is the potential to engineer novel recombinant vaccines by genetically fusing antigens from different pathogens to the enterotoxins.   

Iron acquisition and Bordetella pathogenesis. A second focus of my laboratory is to investigate the mechanisms by which the bacterial pathogens Bordetella pertussis, B. bronchiseptica, and B. parapertussis acquire essential nutrients required to colonize and infect the respiratory tract.  Iron (Fe), an essential nutrient must be obtained by invading bacteria 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 Bordetella pertussis, B. bronchiseptica, and B. parapertussis that mediate acquisition of Fe from the host during infection.  We have identified several gene clusters that encode receptors required for uptake of heme or of siderophores (small molecules which the bacterial elaborate to bind Fe).  We have also discovered a plethora of regulatory proteins which control expression of these various uptake systems (See Figure below).  Our current research is focused on analysis of the receptor proteins and of the members of the family of Extracellular Function Sigma Factor regulators which control expression of these receptors.

Relevant references (1-6):

1.   Nawar, H.F., S. Arce, M.W. Russell, and T.D. Connell.  2007.  Mutants of Type II heat-labile enterotoxin LT-IIa exhibiting altered ganglioside-binding activities and diminished toxicities are potent mucosal adjuvants.  Infection & Immunity 72:621-33.

2.  Arce, S., H.E. Nawar, G. Muehlinghaus, M.W. Russell, T.D Connell.  2007.  "In vitro induction of IgA- and IgM-secreting cells by cholera toxin depends on T-cell help and is mediated by CD154 up-regulation".  Infection & Immunity 75:1413-23.

3.   Shuang, L.,  M. Wang, R. I. Tapping, V. Stepensky, H.F. Nawar, M. Triantafilou, K. Triantafilou, T. D.  Connell, and G. Hajishengallis.  2007.  Ganglioside GD1a is an essential coreceptor for Toll-like Receptor 2 signaling in response to the B subunit of Type IIb enterotoxin.  J. of Biological Chemistry 282:7532-42.

4.   King, N.D., K.F. Smith, and T.D. Connell.  2007.  "Expression of hurP, a gene encoding a prospective site 2 protease, is essential for heme-dependent induction of bhuR in Bordetella bronchiseptica." J. of Bacteriology 189:6266-75.

5.  Mocny, J., J. Olson, and T.D.  Connell.  2007.  The role of spontaneous loss of heme from hemoglobin and myoglobin in iron acquisition by Bordetella bronchiseptica.  Infection & Immunity 75:4857-4866.

6.  Connell, T.D.  2007.  "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 6:821-34.