Michael W. Russell, Ph.D. Professor, Departments of Microbiology & Immunology, and Oral Biology; Witebsky Center for Microbial Pathogenesis and Immunology Phone: (716) 829-2790 Fax: (716) 829-2748 Email: russellm@buffalo.edu

I graduated in Natural Sciences (Biochemistry) from St. John’s College, Cambridge University, England (B.A. Hons., 1966; M.A., 1970), and in Microbiology from Reading University, England (Ph.D., 1973).  My post-doctoral work in Oral Microbiology and Immunology was carried out at Guy's Hospital Medical and Dental Schools, London, England.  In 1979 I moved to the University of Alabama at Birmingham and joined the large Mucosal Immunology group there, eventually becoming Research Professor of Microbiology.  I was elected to fellowship in the American Academy of Microbiology in 2000.  I came to UB as Professor of Microbiology & Immunology, and Oral Biology in 2000, and have served a term as Director of the Witebsky Center (2004-6).  In 2007 I received the IADR Distinguished Scientist Award for Research in Oral Biology.  Whenever I get any spare time I like to travel, watch birds, listen to classical music, or simply enjoy a decent pint, not necessarily in that order.

My research is broadly concerned with the induction and functions of both secretory and circulating IgA antibodies, the immune response against bacterial infections especially of the oral cavity and genital tract, and novel approaches to mucosal vaccine development.  We maintain that IgA antibodies are essentially anti-inflammatory, and can suppress damage to tissues arising from the inflammatory consequences of complement-dependent and opsono-phagocytic defense mechanisms.  These concepts may be applicable to infection-driven inflammatory conditions such as periodontal disease, and coupled with strategies for mucosal immunization may offer novel approaches to the treatment of human disease. 

Several years ago we developed a genetic strategy for coupling protein antigen segments to the highly immunogenic but non-toxic B subunit of cholera toxin (CTB) to make chimeric mucosal immunogens, and we have been investigating the mechanisms underlying the immune response to them.  This approach was initially developed with surface protein adhesin AgI/II of Streptococcus mutans, an antigen that I discovered (along with AgIII) while working in London on a vaccine against dental caries.  While I have maintained my interest in research towards a caries vaccine in collaboration with colleagues at other centers, other applications of this approach to mucosal vaccine development include a vaccine against gonorrhea designed to elicit protective antibodies in the genital tract.  We were among the first to show the efficacy of intranasal immunization for eliciting mucosal antibody responses in the genital tract as well as other secretions.  In collaboration with Dr. Terry Connell, we have evaluated type II heat-labile enterotoxins as antigen-coupled delivery agents and adjuvants that have significantly different immunological properties from cholera toxin, which may therefore be advantageous in vaccine development.  The mechanisms by which these enterotoxins exert their immunomodulatory effects, the regulatory mechanisms involved, and the generation of memory within the mucosal immune system are being pursued.

We have also investigated human mucosal and systemic immune responses against Neisseria gonorrhoeae.  As a result of these studies, we hypothesized that gonococci are capable of interfering with the normal course of an immune response, which may explain the paucity of antibodies developed during human gonorrhea, and the lack of effective immunity induced by natural exposure to it.  We are currently investigating novel concepts regarding the host innate immune-inflammatory response to gonococci.  In collaboration with other centers we are also investigating possibilities for developing a mucosal vaccine against gonorrhea utilizing enterotoxins as immunomodulators or delivery agents for mucosal administration.

The Russell lab:

Brandon Feinen, BS (SUNY at Fredonia)
Weiwei Zhao, PhD (Sun Yet-sen University, China)
Dawn Both-Kim, MSc (SUNY at Buffalo)

Selected publications (out of 204):

Hajishengallis, G., Hollingshead, S.K., Koga, T., and Russell, M.W.  Mucosal immunization with a bacterial protein antigen genetically coupled to cholera toxin A2/B subunits.  J. Immunol. 154: 4322-4332 (1995).

Nikolova, E.B. and Russell, M.W.  Dual function of human IgA antibodies: inhibition of phagocytosis in circulating neutrophils and enhancement of responses in IL-8-stimulated cells.  J. Leukocyte Biol. 57: 875-882 (1995).

Russell, M.W., Moldoveanu, Z., White, P.L., Sibert, G.J., Mestecky, J., and Michalek, S.M.  Salivary, nasal, genital, and systemic antibody responses in monkeys immunized intranasally with a bacterial protein antigen and the cholera toxin B subunit.  Infect. Immun. 64: 1272-1283 (1996).

Wu, H.-Y., Nahm, M., Guo, Y., Russell, M.W., and Briles, D.E.  Intranasal immunization of mice with PspA (pneumococcal surface protein A) can prevent intranasal carriage, pulmonary infection, and sepsis with Streptococcus pneumoniae.  J. Infect. Dis. 175: 839-846  (1997).

Wu, H.-Y., Nguyen, H., and Russell, M.W.  Nasal lymphoid tissue (NALT) as a mucosal immune inductive site.  Scand. J. Immunol. 46: 506-513 (1997).

Hedges, S.R., Sibley, D., Mayo, M.S., Hook, E.W., and Russell, M.W.  Cytokine and antibody responses in women infected with Neisseria gonorrhoeae: effects of concomitant infections.   J. Infect. Dis. 178: 742-751 (1998).

Hedges, S.R., Mayo, M.S., Kallman, L., Mestecky, J., Hook, E.W., Russell, M.W.  Evaluation of immunoglobulin A1 (IgA1) protease and IgA1 protease-inhibitory activity in human female genital infection with Neisseria gonorrhoeae.  Infect. Immun. 66: 5826-5832 (1998).

Hedges, S.R., Mayo, M.S., Mestecky, J., Hook, E.W., and Russell, M.W.  Limited local and systemic antibody responses to Neisseria gonorrhoeae during uncomplicated genital infections.  Infect. Immun. 67: 3937-3946 (1999).

Russell, M.W. and Sibley, D.A.  IgA as an anti-inflammatory regulator of immunity. Oral Dis. 5: 55-56 (1999).

Martin, M.H., Metzger, D.J., Michalek, S.M., Connell, T.D. and Russell, M.W. Comparative analysis of the mucosal adjuvanticity of the type II heat-labile enterotoxins, LT-IIa and LT-IIb. Infect. Immun. 68: 281-287 (2000).

Wu, H.-Y., Abdu, S., Stinson, D. and Russell, M.W.  Generation of female genital tract antibody responses by local or central (common) mucosal immunization.  Infect. Immun. 68: 5539-5545 (2000).

Martin, M., Hajishengallis, G., Metzger, D.J., Michalek, S.M., Connell, T.D. and Russell, M.W.  Recombinant antigen-enterotoxin A2/B chimeric mucosal immunogens differentially enhance antibody responses and B7-dependent co-stimulation of T cells. Infect. Immun. 69: 252-261 (2001).

Harrod, T., Martin, M. and Russell, M.W. Long-term persistence and recall of immune responses in aged mice after mucosal immunization.  Oral Microbiol. Immunol. 16: 170-177 (2001).

Martin, M.H., Metzger, D.J., Michalek, S.M., Connell, T.D., and Russell, M.W.  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. 69: 4486-4492 (2001).

Smith, P.D., Smythies, L.E., Mosteller-Barnum, M., Sibley, D.A., Russell, M.W., Merger, M., Sellers, M.T., Orenstein, J.M., Shimada, T., Graham, M.F., and Kubagawa, H.  Intestinal macrophages lack CD14 and CD89 and consequently are down-regulated for LPS- and IgA-mediated activities.   J. Immunol. 167: 2651-2656 (2001).

Jespersgaard, C., Zhang, P., Hajishengallis, G., Russell, M.W., and Michalek, S.M.  Effect of attenuated Salmonella enteritica serovar Typhimurium expressing a Streptococcus mutans antigen on secondary responses to the cloned protein.  Infect. Immun. 69: 6604-6611 (2001).
Russell, M.W.  Immunization for protection of the reproductive tract: a review. Am. J. Reprod. Immunol. 47: 265-268 (2002).

Jespersgaard, C., Hajishengallis, G., Russell, M.W., and Michalek, S.M.  Identification and characterization of a nonimmunoglobulin factor in human saliva that inhibits Streptococcus mutans glucosyltransferase.  Infect. Immun. 70: 1136-1142 (2002)

Hajishengallis, G., Martin, M., Sojar, H.T., Sharma, A., Schifferle, R.E., DeNardin, E., Russell, M.W., and Genco, R.J.  Proinflammatory cytokine induction by bacterial protein adhesins via the CD14/toll-like receptor system. Clin. Diag. Lab. Immunol. 9: 403-411 (2002).

Russell, M.W. and Mestecky, J.  Humoral immune responses to microbial infections in the genital tract. Microb. Infect. 4: 667-677 (2002).

Russell, M.W.  Mucosal immunity. Chapter 5, p 64-80.  In New Bacterial Vaccines (Eds. Ellis, R.W. and Brodeur, B.R.) Eurekah.com, Georgetown TX and Kluwer Academic/Plenum, New York (2003).

Russell, M.W., Childers, N.K., Michalek, S.M., Smith, D.J., and Taubman, M.A.  A caries vaccine? The state of the science of immunization against dental caries.  Caries Res. 38: 230-235 (2004).

Hajishengallis, G., Nawar, H., Tapping, R.I., Russell, M.W., and Connell, T.D.  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. 72: 6351-6358 (2004).

Russell, M.W., Bobek, L.A., Brock, J.H., Hajishengallis, G., and Tenovuo, J.  Innate humoral defense factors.  Chapter 5, p 73-93.  In Mucosal Immunology, 3rd edition (Eds. Mestecky, J., Bienenstock, J., Lamm, M.E., Mayer, L., Strober, W., McGhee, J.R.) Academic Press/Elsevier, San Diego (2005).

Peppard, J.V., Kaetzel, C.S., and Russell, M.W.  Phylogeny and comparative physiology of IgA.  Chapter 11, p. 195-210.   In Mucosal Immunology, 3rd edition (Eds. Mestecky, J., Bienenstock, J., Lamm, M.E., Mayer, L., Strober, W., McGhee, J.R.) Academic Press/Elsevier, San Diego (2005).

Russell, M.W. and Kilian, M.  Biological activities of IgA.  Chapter 14, p 267-289.  In Mucosal Immunology, 3rd edition (Eds. Mestecky, J., Bienenstock, J., Lamm, M.E., Mayer, L., Strober, W., McGhee, J.R.) Academic Press/Elsevier, San Diego (2005).

Kilian, M. and Russell, M.W.  Microbial evasion of IgA functions.  Chapter 15, p. 291-303.  In Mucosal Immunology, 3rd edition (Eds. Mestecky, J., Bienenstock, J., Lamm, M.E., Mayer, L., Strober, W., McGhee, J.R.) Academic Press/Elsevier, San Diego (2005).

Russell, M.W., Sparling, P.F., Morrison, R.P., Cauci, S., Fidel, P.L., Martin, D., Hook, E.W., and Mestecky, J.  Mucosal immunology of sexually transmitted diseases.  Chapter 99, p 1693-1720.  In Mucosal Immunology, 3rd edition (Eds. Mestecky, J., Bienenstock, J., Lamm, M.E., Mayer, L., Strober, W., McGhee, J.R.) Academic Press/Elsevier, San Diego (2005).

Nawar, H., Arce, S., Russell, M.W., and Connell, T.D.  Mucosal adjuvant properties of mutant LT-IIa and LT-IIb enterotoxins that exhibit altered ganglioside-binding activities.  Infect. Immun. 73: 1330-1342 (2005).

Hajishengallis, G., Tapping, R.I., Martin, M.H., Nawar, H., Lyle, E.A., Russell, M.W., and Connell, T.D.  Toll-like receptor 2 mediates cellular activation by the B subunits of type II heat-labile enterotoxins.  Infect. Immun. 73: 1343-1349 (2005).

Arce, S., Nawar, H.F., Russell, M.W., and Connell, T.D.  Differential binding of Escherichia coli enterotoxins LT-IIa, LT-IIb and of cholera toxin elicits differences in apoptosis, proliferation, and activation of lymphoid cells.  Infect. Immun. 73: 2718-2727 (2005).

Price, G.A., Russell, M.W., and Cornelissen, C.N.  Intranasal administration of recombinant Neisseria gonorrhoeae transferrin binding proteins A and B conjugated to the cholera toxin B subunit induces systemic and vaginal antibodies in mice.  Infect. Immun. 73: 3945-3953 (2005).

Hajishengallis, G., Arce, S., Gockel, C.M., Connell, T.D., and Russell, M.W.  Immunomodulation with enterotoxins for the generation of secretory immunity or tolerance:  applications for oral infections.  J. Dent. Res. 84: 1104-1116 (2005).

Gockel, C.M. and Russell, M.W. Induction and recall of immune memory by mucosal immunization with a non-toxic recombinant enterotoxin-based chimeric protein.  Immunology 116: 477-486 (2005).

Nawar, H.F., Arce, S., Russell, M.W., and Connell, T.D.  Mutants of type II heat-labile LT-IIa with altered ganglioside-binding activities and diminished toxicities are potent mucosal adjuvants.  Infect. Immun. 75: 621-633 (2007).

Arce, S., Nawar, H.F., Muehlinghaus, G., Russell, M.W., and Connell, T.D.  In vitro induction of IgA- and IgM-secreting plasma blasts by cholera toxin depends upon T cell help and is mediated by CD154 up-regulation and inhibition of IFN-g synthesis.  Infect. Immun. 75: 1413-1423 (2007).

Liang, S., Wang, M., Triantafilou, K., Triantafilou, M., Nawar, H.F., Russell, M.W., Connell T.D., and 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. 178: 4811-4819 (2007).

Price, G.A., Masri, H.P., Russell, M.W., and Cornelissen, C.N.  Gonococcal transferrin binding protein chimeras induce bactericidal and growth inhibitory antibodies in mice. Vaccine 25: 7247-7260 (2007).

Russell, M.W.  Biological functions of IgA, Chapter 6, pp 144-172.  In Mucosal Immune Defense: Immunoglobulin A (Ed. Kaetzel, C.S.), Springer, New York (2007).

Mestecky, J., Russell, M.W., and Elson, C.O.  Perspectives on mucosal vaccines: is oral tolerance a barrier?  J. Immunol. 179: 5633-5638 (2007).

Hajishengallis, G., and Russell, M.W.  Molecular approaches to vaccination against oral infections, Chapter 11, pp 257-285.  In Molecular Oral Microbiology (Ed. Rogers, A.H.), Caister Academic Press, Norfolk, U.K. (2008).

Brandtzaeg, P., Kiyono, H., Pabst, R., and Russell, M.W.  Terminology: Nomenclature of mucosa-associated lymphoid tissue.  Mucosal Immunol. 1: 31-37 (2008).

Patents:

US patent #6,030,624; 29 February 2000. “Mucosal Immunogens for Novel Vaccines”
US patent #6,846,488; 25 January 2005. “Chimeric Antigen-Enterotoxin Mucosal Immunogens”