Lee M. Wetzler, M.D.
Professor of Medicine
Associate Professor of Microbiology
650 Albany Street
Office: X638; 617-414-4394
Lab: X630; 617-414-5224
M.D. SUNY/Upstate Medical Center, Syracuse
My laboratory is interested in bacterial pathogenesis and the generation of protective immune responses. Our work mainly centers on the pathogenic neisseria, Neisseria gonorrhoeae and Neisseria meningitidis. We have been using the major outer membrane protein of the neisseria, termed porins, as potential vaccine candidates. We are currently involved in a collaboration with the Rockefeller University and the NIH in bringing to human trails a potential anti-gonococcal vaccine utilizing the gonococcal porins inserted in liposomes.
A unique property of these porins is their ability to act as immune stimulators and augment the immune response to poorly immunogenic substances. Their adjuvant activity is likely due to their ability to act as B cell mitogens, increasing the expression of the T cell costimulatory factor, B7-2 on the surface of B cells (and likely other antigen presenting cells). Neisserial porin is also able to induce maturation of dendritic cells and improves their ability to present antigen to T cells. We are also investigating the signal transduction events induced by the porins. We have found that Neisserial poirns can induce protein tyrosine kinase activity and NF-kappaB nuclear translocation, both essential in their ability to induce B7-2 and class II MHC expression. Porin can also induce MAPKK (MEK) activity to elicit phosphorylation and activation of MAPK1/2 (Erk1/2), but not p38 or jnk MAPKs. We have preliminary data that suggests that the majority of these effects is due to an interaction of Neisserial porin wihtt eh pattern recognition recpeptor TLR2.
More recent data demonstrates that these porins also seem to effect the susceptibility of activated B cells to apoptosis. We are currently investigating the mechanism of this effect and have shown that it is due to an interaction of the porins with eukaryotic cell mitochondria and stabilization of the mitcochondrial membrane that is normally perturbed by apoptotic stimuli.
Another group of studies we are performing is investigation into the relationship between the immune response to gonococcal porins in patients and partners of patients with gonorrhea and possible protective immunity. We are measuring the T cell response in female partners of men with gonorrhea and relating these findings to whether the female partners in turn get gonorrhea. This is being performed as part of the STD-CRC program project grant that our division has received.
- Massari, P., Gunawardana, J., Liu, X., Wetzler, L.M. 2010. Meningococcal porin PorB prevents cellular apoptosis in a toll-like receptor 2- and NF-kappaB-independent manner. Infect. Immun. 78:994-1003. PMID: 20028813.
- Wetzler, L.M. 2010. Innate Immune Function of the Neisserial Porins and the Relationship to Vaccine Adjuvant Activity, Future Microbiology 5(5):749-58. PMID: 20441547
- Chiavolini, D., Rangel-Moreno, J., Berg, G., Christian, K., Oliveira-Nascimento, L., Weir, S., Alroy, J., Randall, T.D., and Wetzler, L.M. 2010. Bronchus-associated lymphoid tissue (BALT) and survival in a vaccine mouse model of tularemia. PLoS One 5(6):e11156. PMID: 20585390
- Massari, P., Wetzler, L.M. 2012. Analysis of parameters associated with prevention of cellular apoptosis by pathogenic neisseriae and purified porins. Methods Mol. Biol. 799:319-41. PubMed PMID: 21993654
- Oliveira-Nascimento L., Massari P., Wetzler L.M.. 2012. The Role of TLR2 in Infection and Immunity. Front. Immunol. 3:79. Epub 2012 Apr 18. PubMed PMID: 22566960; PubMed Central PMCID: PMC 3342043
- Platt, A, Wetzler L. M. 2013 Innate immunity and vaccines. Curr. Top. Med. Chem. 13(20):2597-608. PubMed PMID: 24066890
- Platt, A., Macleod, H., Massari, P., Liu, X., Wetzler, L.M., 2013. In Vivo and In Vitro Characterization of the Immune Stimulating Activity of the Neisserial Porin PorB. PLoS One 8(12):e82171. PubMed PMID: 24349212
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