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Faculty Detail    
Name SUZANNE M MICHALEK
  
Campus Address BBRB 720 Zip 2170
Phone  (205) 934-3470
E-mail  suemich@uab.edu
Other websites Publications
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Microbiology  Microbiology Professor Emeritus
Center  Comp Arthritis, MSK, Bone & Autoimmunity Ctr  Comp Arthritis, MSK, Bone & Autoimmunity Ctr Professor Emeritus
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor Emeritus
Center  GL Ctr for Craniofacial, Oral, & Dental Disorders  GL Ctr for Craniofacial, Oral, & Dental Disorders Professor Emeritus
Center  Nephrology Research & Training Center  Nephrology Research & Training Center Professor Emeritus
Center  UAB Immunology Institute  UAB Immunology Institute Professor Emeritus
Center  UWIRC Microbiome Center  UWIRC Microbiome Center Professor Emeritus

Graduate Biomedical Sciences Affiliations
Cellular and Molecular Biology Program 
Immunology 
Medical Scientist Training Program 
Microbiology 

Biographical Sketch 
Suzanne M. Michalek is Professor of the Department of Microbiology. Following her initial training in genetics (B.S., 1967; M.S., 1968), she initiated studies in immunology at the University of Chicago with emphasis on the mucosal immune system. Her studies at UAB (Ph.D., 1976) on the induction of salivary IgA antibody responses protective against Streptococcus mutans-induced dental caries provided evidence for the existence of a common mucosal immune system and for the development of a human oral vaccine against dental caries. Following postdoctoral studies at NIH on the effects of bacterial LPS on the host's immune system, she joined the Mucosal Immunology Group at UAB (1979).

Society Memberships
Organization Name Position Held Org Link
American Academy of Microbiology      
American Society for Microbiology      
International and American Association for Dental Research      
Society for Leukocyte Biology      
Society for Mucosal Immunology      
The American Association of Immunologists      
The International Endotoxin Society      
 



Research/Clinical Interest
Title
Immunological mechanisms involved in host/microbial interactions, and development of mucosal vaccines against infectious agents
Description
My research program centers around two major themes: 1) understanding immunological mechanisms involved in host/microbial interactions, with emphasis on host responses to the pathogens Porphyromonas gingivalis and Francisella tularensis, and 2) the development of mucosal vaccines against infectious diseases. P. gingivalis is involved in the development of periodontal disease, an inflammatory process that has also been linked to systemic disorders such as cardiovascular disease. Our studies with P. gingivalis focus on the cell signaling molecules and transcription factors involved in the host response this pathogen. F. tularensis is the cause of tularemia. Due to its ability to infect via multiple routes, its ease of dissemination, and its high infectivity, morbidity and rate of mortality, F. tularensis is considered a bioterrorism agent. The nature of the inflammatory response induced by Francisella infection is a critical determining factor of the outcome of the infectious process. Our studies are directed to delineate the signaling pathways and potential target molecules that could be implicated in the inflammatory process. Through a better understanding of the cellular mechanisms involved in the host immune response to these pathogens, we hope to identify target molecules for the development of protective immunotherapeutic approaches. Since greater than 95% of all infectious disease involve the colonization or penetration of our mucosal surfaces, our mucosal immune system serves as our first line of defense against pathogens. Therefore, we have devoted considerable effort to understanding the mucosal immune system and in developing mucosal vaccines against microbial pathogens. Current in vivo studies in adults and children are testing the effectiveness of our mucosal vaccine consisting of recombinant microbial polypeptides from Streptococcus mutans (the principle etiologic agent of tooth decay) in inducing mucosal as well as systemic immune responses that protect against dental caries. We have also developed a mucosal vaccine that confers greater than 80% protection against respiratory infection by the biologic threat agent F. tularenesis. These studies are being done in a murine model. Ongoing studies are designed to test the effectiveness of our vaccine in protecting against highly virulent forms of this pathogen and in additional model systems. We also plan on determining the effectiveness of our vaccine in the elderly, since it is well know that age does affect our immune system, making us more susceptible to diseases. It is possible that our vaccine may need to be modified by including additional antigens/adjuvants to make it even more effective in inducing protective responses in the population at large. Our studies should help in the development of means to treat/prevent infectious diseases via therapeutic approaches and/or mucosal vaccines. Since microbial pathogens, e.g., P. gingivalis, can alter the outcome of systemic diseases, such as kidney disease, cancer or depression, we are also investigating the cellular mechanisms involved in these processes in an effort to define therapeutic approaches that would help in the treatment of systemic diseases/disorders.

Selected Publications 
Publication PUBMEDID
Lynch, D.J., Michalek, S.M., Zhu, M., Drake, D., Qian, F., and Banas, J.A. 2013. Cariogenicity of Streptococcus mutans glucan-binding protein deletion mutants. Oral Health Dent. Manag. 12:191-199.  PMC4437697 
Wang, P., Dai, Q., Thogaripally, P., Zang, P., and Michalek, S.M. 2013. Synthesis of QS-21-based immunoadjuvants. J. Org. Chem. 78:11525-11534.  PMC3937667 
Edwards, M.W., Aultman, J.A., Harber, G., Bhatt, J.M., Sztul, E., Xu, Q., Zhang, P., Michalek, S.M., and Katz, J. 2013. Role of mTOR downstream effector signaling molecules in Francisella tularensis internalization by murine macrophages. PLoS ONE 8(12): e83226.  PMC3849438 
Beurel, E., Kaidanovich-Beilin, O., Yeh, W-I., Song, L., Palomo, V., Michalek, S.M., Woodgett, J.R., Harrington, L.E., Eldar-Finkelman, H., and Jope, R.S. 2013. Regulation of Th1 cells and experimental autoimmune encephalomyelitis by glycogen synthase kinase-3. J. Immunol.190:5000-5011.  PMC3660233 
Speer, A., Shrestha, T.B., Bossmann, S.H., Basaraba, R.J., Harber, G.J., Michalek, S.M., Niederweis, M., Kutsch, O., and Wolschendorf, F. 2013. Copper-boosting compounds: a novel concept for anti-mycobacterial drug discovery. Antimicrob. Agents Chemother. 57:1089-1091.  PMC3553712 
Gaddis, D.E., Maynard, C.L. Weaver, C.T., Michalek, S.M., and Katz, J. 2013. Role of TLR2 dependent-IL-10 production in the inhibition of the initial IFN- T cell response to Porphyromonas gingivalis. J. Leukoc. Biol. 93:21-31.  PMC3525832 
Ashtekar A.R., Katz, J., Xu, Q., and Michalek, S.M. 2012. A mucosal subunit vaccine protects against lethal respiratory infection with Francisella tularensis LVS. PLoS ONE 7(11): e50460. Doi:10.1371/journal.pone.0050460.  PMC3508931 
Palmer, S.R., Crowley, P.J., Oli, M.W., Ruelf, M.A., Michalek, S.M., and Brady, L.J. 2012. YidC1 and YidC2 are functionally distinct proteins involved in protein secretion, biofilm formation and cariogenicity of Streptococcus mutans. Microbiology 158:1702-1712.  PMC3542144 
Jules, J., Zhang, P., Ashley, J.W., Wei, S., Shi, Z., Lui, J., Michalek, S.M., and Feng. X. 2012. Molecular basis of requirement of receptor activator of nuclear factor B signaling for interleukin 1-mediate osteoclastogenesis. J. Biol. Chem. 287:15728-15738.  PMC3346127 
Xu, Q., Katz, J., Zhang, P., Ashtekar, A.R., Gaddis, D.E., Fan, M., and Michalek, S.M. 2011. Contribution of a Streptococcus mutans antigen expressed by a Salmonella vector vaccine in dendritic cell activation. Infect. Immun. 79:3792-3800.  PMC3165457 
Zhang, P., Liu, J., Xu, Q., Harber, G., Feng, X., Michalek, S.M., and Katz, J. 2011. TLR2-dependent modulation of osteoclastogenesis by Porphyromonas gingivalis through differential induction of NFATc1 and NF-B. J. Biol. Chem. 286:24159-24169.  PMC3129197 
Gaddis, D.E., Michalek, S.M., and Katz, J. 2011. TLR4 signaling via MyD88 and TRIF differentially shape the CD4+ T cell response to Porphyromonas gingivalis hemagglutinin B. J. Immunol. 186:5772-5783.  PMC3809913 
Beurel, E., Yeh, W.I., Michalek, S.M., Harrington, L.E., and Jope, P.S. 2011. Glycogen synthase kinase-3 is an early determinant in the differentiation of pathogenic Th17 cells. J. Immunol. 186:1391-1398.  PMC3125578 
Xiang, X., Liu, Y., Zhuang, X., Zhang, S., Michalek, S., Taylor, D.D., Grizzle, W., and Zhang, H.G. 2010. TLR2-mediated expansion of MDSCs is dependent on the source of tumor exosomes. Am. J. Pathol. 177:1606-1610.  PMC2947257 
Salam, M.A., Katz, J., and Michalek, S.M. 2010. Role of Toll-like receptors in host responses to a virulence antigen of Streptococcus mutans expressed by a recombinant, attenuated Salmonella vector vaccine. Vaccine 28:4928-4936.  PMC2910446 
Liu, Y., Xiang, X., Zhuang, X., Zhang, S., Liu, C., Cheng, Z., Michalek, S., Grizzle, W., and Zhang, H-G. 2010. Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells. Am. J. Pathol. 176:2490-2499.  PMC2861113 
Larson, M.R., Rajashankar, K.R., Patel, M.H., Robinette, R.A., Crowley, P.J., Michalek, S., Brady, L.J., and Deivanayagam, C. 2010. Elongated fibrillar structure of a streptococcal adhesin assembled by the high-affinity association of - and PPII-helices. Proc. Natl. Acad. Sci. USA 107:5983-5988.  PMC2851892 
Beurel, E., Michalek, S.M., and Jope, R.S. 2009. Innate and adaptive immune responses regulated by glycogen synthase kinase-3 (GSK3). Trends Immunol. 31:24-31.  PMC2818223 
Deng, Z-B., Poliakov, A., Hardy, R.W., Clements, R., Liu, C., Liu, Y., Wang, J., Xiang, X., Zhang, S., Zhuang, X., Shah, S.V., Sun, D., Michalek, S., Grizzle, W.E., Garvey, T., Mobley, J., and Zhang, H-G. 2009. Adipose tissue exosome-like vesicles mediate activation of macrophage-induced insulin resistance. Diabetes 58:2498-2505.  PMC2768161 
Deng, Z-B., Liu, Y., Liu, C., Xiang, X., Wang, J., Cheng, Z., Shah, S.V., Zhang, S., Zhang, L., Zhuang, X., Michalek, S., Grizzle, W.E., and Zhang, H-G. 2009. Immature myeloid cells induced by a high fat diet contribute to liver inflammation. Hepatology 50:1412-1420.  PMC2852608 
Zhang, P., Katz, J., and Michalek, S.M. 2009. Glycogen synthase kinase-3β inhibition suppresses the inflammatory response to Francisella infection and protects against tularemia in mice. Mol. Immunol. 46:677-687.   PMC3033759 
Gaddis, D.E., Michalek, S.M. and Katz, J. 2009. Requirement of TLR4 and CD14 in dendritic cell activation by hemagglutinin B from Porphyromonas gingivalis. Mol. Immunol. 46:2493-2504.  PMC2763909 
Liu, J., Wang, S., Zhang, P., Said-Al-Maief, N., Michalek, S.M., and Feng, X. 2009. Molecular mechanism of the bifunctional role of lipopolysaccharide in osteoclastogenesis. J. Biol. Chem. 284: 12512-12523.  PMC2673317 
Ashtekar, A.R., Zhang, P., Katz, J., Deivanayagam, C.C.S., Rallabhandi, P., Vogel, S.N., and Michalek, S.M. 2008. TLR4-mediated activation of dendritic cells by the heat shock protein DnaK from Francisella tularensis. J. Leukoc. Biol. 84:1434-46.  PMC2614597 
Chen, Y., Wang, X., Di, L., Fu, G., Chen, Y., Bai, L., Liu, J., Feng, X., McDonald, J.M., Michalek, S., He, Y., Yu, M., Fu, Y., Wen, R., and Wu, H. 2008. Phospholipase Cγ2 mediates RANKL-stimulated lymph node organogenesis and osteoclastogenesis. J. Biol. Chem. 283:29593-29601.  PMC2570883 
Yang, D., Chen, Q., Su, S.B., Zhang, P., Kurosaka, K., Caspi, R.R., Michalek, S.M., Rosenberg, H.F., Zhang, N., and Oppenheim, J.J. 2008. Eosinophil-derived neurotoxin acts as an alarmin to activate the TLR2-MyD88 signal pathway in dendritic cells and enhances Th2 immune responses. J. Exp. Med. 205: 79-90.  PMC2234357 
Seo, H., Michalek, S.M., and Nahm, M.H. 2008. Lipoteichoic acid is important in innate immune responses to gram-positive bacteria. Infect. Immun. 76: 206-213.  PMC2223632 
Cole, L.E., Shirey, K.A., Barry, E., Santiago, A., Rallabhandi, P., Elkins, K.L., Puche, A., Michalek, S.M., and Vogel, S.N. 2007. TLR2-mediated signaling requirements for Francisella tularensis LVS infection of murine macrophages. Infect. Immun. 75: 4127-4137.  PMC1951974 
Zhang, P., Lewis, J.P., Michalek, S.M., and Katz, J. 2007. Role of CD80 and CD86 in host immune responses to the recombinant hemagglutinin domain of Porphyromonas gingivalis gingipain and in the adjuvanticity of cholera toxin B and monophosphoryl lipid A. Vaccine 25: 6201-6210.  PMC2699271 
Banas, J.A., Miller, J.D., Fuschino, M.E., Hazlett, K.R.O., Toyofuku, W., Porter, K.A., Reutzel, S.B., Florczyk, M.A., Mc Donough, K.A., and Michalek, S.M. 2007. Evidence that accumulation of mutants in a biofilm reflects natural selection rather than stress-induced adaptive mutation. Appl. Environ. Microbiol. 73: 357-361.  PMC17977100 
Childers, N.K., Li, F., Dasanayake, A.P., Li, Y., Kirk, K., Michalek, S.M. 2006. Immune response in humans to a nasal boost with Streptococcus mutans antigens. Oral Microbiol. Immunol. 21:309-313.   
Salam, M.A., Katz, J., Zhang, P., Hajishengallis, G., and Michalek, S.M. 2006. Immunogenicity of Salmonella vector vaccines expressing SBR of Streptococcus mutans under the control of a T7-nirB (dual) promoter system. Vaccine 24:5003-15.   
Cole, L.E., Elkins, K.L., Michalek, S.M., Qureshi, N., Eaton, L.J., Rallabhandi, P., Cuesta, N., and Vogel, S.N. 2006. Immunologic consequences of Francisella tularensis live vaccine strain infection: role of the innate immune response in infection and immunity. J. Immunol. 176:6888-6899.   
Katz, J., Zhang, P., Martin, M., Vogel, S.N., and Michalek, S.M. 2006. Toll-like receptor 2 is required for inflammatory responses to Francisella tularensis LVS. Infect. Immun. 74:2809-2816.   
Han, S.H., Kim, J.H., Martin, M., Chung, G-H., Michalek, S.M., and Nahm, M.H. 2005. Lipoteichoic acid-induced nitric oxide production depends on the activation of PAF receptor and Jak2. J. Immunol.176:573-579.   
Zhang, P., Yang, Q-B., Balkovetz, D., Lewis, J.P., Clements, J.D., Michalek, S.M., and Katz, J. 2005. Effectiveness of the B subunit of cholera toxin in potentiating immune responses to the recominant hemagglutinin/adhesin domain of the gingipain Kgp from Porphyromonas gingivalis. Vaccine 23:4734-4744.   
Pino, O., Martin, M., and Michalek, S.M. 2005. Cellular mechanisms of the adjuvant activity of the flagellin component FljB of Salmonella typhimurium to potentiate mucosal and systemic responses. Infect. Immun. 73:6763-6770.   
Martin, M., Rehani, K., Jope, R.S., Michalek, S.M. 2005. Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase. Nature Immunol. 6:777-784.   
Zhang, P., Martin, M., Michalek, S.M, and Katz, J. 2005. Role of mitogen-activated protein kinases and NF-ƒÛB in the regulation of pro- and anti-inflammatory cytokines by Porphyromonas gingivalis hemagglutinin B. Infect. Immun. 73:3990-3998.   
Menendez, A., Li, F., Michalek, S.M., Kirk, K., Makhija, S.K., Childers, N.K., 2004. Comparative analysis of the antibacterial effects of combined mouthrinses on Streptococcus mutans. Oral Microbiol. Immunol. 20:31-34.   
Garcia, C.A., Martin, M., and Michalek, S.M. 2004. Role of B7 costimulatory molecules in mediating systemic and mucosal antibody responses to an attenuated Salmonella enterica serovar Typhimurium and its cloned antigen. Infect. Immun. 72:5824-5831.   
Russell, M.W., Childers, N.K., Michalek, S.M., Smith, D.J., Taubman, M.A.. 2004. A caries vaccine? The state of the science of immunization against dental caries. Caries Res. 38:230-235.    
Zhang, P., Martin, M., Yang, Q-B., Michalek, S.M., and Katz, J. 2004. Role of B7 costimulatory molecules in immune responses and T-helper cell differentiation to recombinant HagB from Prophyromonas gingivalis. Infect. Immun. 72:637-644.   
Han, S.H., Kim, J.H., Martin, M., Michalek, S.M., and Nahm, M.H. 2003. Pneumococcal lipoteichoic acid (LTA) is not as potent as staphylococcal LTA in stimulating Toll-like receptor 2. Infect. Immun. 71:5541-5548.   
Zhang, P., Yang, Q-B., Marciani, D.J., Martin, M., Clements, J.D., Michalek, S.M., and Katz, J. 2003. Effectiveness of the quillaja saponin semi-synthetic analog GPI-0100 in potentiating mucosal and systemic responses to recombinant HagB from Porphyromonas gingivalis. Vaccine 21:4459-4471.   
Martin, M., Schifferle, R.E., Cuesta, N., Vogel, S.N., Katz, J., and Michalek, S.M. 2003. Role of the P13 kinases-Akt pathway in the regulation of IL-10 and IL-12 by Porphyromonas gingivalis lipopolysaccharide. J. Immunol. 171:717-725.   
 

Keywords
mucosal vaccines, inflammation, TLRs, T cell, cytokines, signaling pathways