Elaine Tuomanen, MD

Elaine Tuomanen, MD

Member, St. Jude Faculty
Chair, Infectious Diseases
Director, Children's Infection Defense Center (CIDC)
Co-Leader, Bacterial Pathogenesis, CIDC

Departments

Infectious Diseases

Contact Information

Elaine Tuomanen, MD
Infectious Diseases
MS320, Room E8057
St. Jude Children's Research Hospital
262 Danny Thomas Place
Memphis, TN 38105-3678
Email: elaine.tuomanen@stjude.org
Phone: (901) 595-3114
FAX: (901) 505-3099

Education

MD - McGill University, University Scholar


Research Interests

Molecular pathogenesis of Streptococcus pneumoniae invasion and inflammation

The major focus of this research is the molecular pathogenesis of invasion and inflammation induced by Streptococcus pneumoniae, the leading invasive bacterial pathogen of children. Virulence genes are identified by genetic screens as well as by analysis of the completed genome. To evaluate gene function, we test the mutants' abilities (e.g., adherence, invasion, transmigration, induction of cytokine production, and cytoxicity) in models of the pulmonary epithelium, vascular endothelium, and blood-brain barrier. Cell lines and transfected cell systems augment this study with particular emphasis on perturbations in the biology of selectins, integrins, matrix adhesion, and chemokine receptors. By using these systems, a model of pneumococcal disease has been assembled. The bacteria adhere to nasopharyngeal, pulmonary, and endothelial cells. Upon cellular activation, the bacteria then adhere to chemokine receptors, particularly the platelet-activating factor receptor. This interaction allows bacterial entry into cells and results in transmigration. This sequence of events is then tested in mouse models of pneumonia and meningitis. The strengths of this laboratory are in the study of gram-positive molecular biology and genomics; gram-positive interactions with human cells and models of disease; and the emerging relationship of transformation, virulence, and autolysis. Areas of medical therapeutics applicable to this work include pneumococcal vaccine design, intervention in gram-positive sepsis/meningitis, new antibiotic development strategies, and interruption of the spread of genetic elements responsible for antibiotic resistance.


Selected Publications

Orihuela CJ, Mahdavi J, Thornton J, Mann B, Wooldridge KG, Abouseada N, Oldfield NJ, Self T, Ala¹Aldeen DAA, Tuomanen E. Laminin receptor initiates contact of bacteria with the blood brain barrier. J Clin Invest Jun;119(6):1638-46, 2009.

Miller ML, Gao G, Pestina T, Persons D, Tuomanen E. Hypersusceptibility to invasive pneumococcal infection in experimental sickle cell disease involves PAF receptor. J Infect Dis 195:581-584, 2007.

Marks M, Burns T, Abadi M, Seyoum B, Thornton J, Tuomanen E, Pirofsky L-A. The influence of peripheral neutropenia on the course of experimental pneumococcal pneumonia in mice. Infect Immun 75:1586-1597, 2007.

Fillon S, Soulis K, Murti G, Kaushal D, Radin JN, Orihuela CJ, Murray PJ, Weber JR, Tuomanen EI. Platelet activating factor receptor and innate immunity: uptake of Gram positive bacterial cell wall into host cells and cell-specific pathophysiology. J Immunol 177:6182-6191, 2006.

Orihuela CJ, Fillon S, Smith-Sielicki SH, El Kasmi KC, Gao G, Soulis K, Patil A, Murray PJ, Tuomanen EI. Cell wall-mediated neuronal damage in early sepsis. Infect Immun 74:3783-3789, 2006.

Obert C, Sublett J, Kaushal D, Barton T, Tuomanen EI, Orihuela CJ. Identification of the Streptococcus pneumoniae core genome and regions of diversity correlated with invasive pneumococcal disease. Infect Immun 74:4766-4777, 2006.

Radin JN, Orihuela CJ, Murti G, Guglielmo C, Murray PJ, Tuomanen EI. Β-arrestin 1 determines the traffic pattern of PAFr-mediated endocytosis of Streptococcus pneumoniae. Infect Immun 73:7827-7835, 2005.

Luo R, Mann B, Lewis WS, Rowe A, Heath R, Stewart ML, Hamburger AE, Sivakolundu S, Lacy E, Bjorkman PJ, Tuomanen E, Kriwacki RW. Solution structure of choline binding protein A of Streptococcus pneumoniae reveals a novel mode of interaction with its human receptor, plgR. EMBO 24:34-43, 2005.

Mitchell L, Smith SH, Braun JS, Herzog K-H, Weber JR, Tuomanen EI. Dual phases of apoptosis in pneumococcal meningitis. J Infect Dis 190:2039-2046, 2004.

Orihuela CJ, Gao G, Francis KP, Yu J, Tuomane EI. Tissue-specific contributions of pneumococcal virulence factors to pathogenesis. J Infect Dis 190:1661-1669, 2004.

Zweigner J, Jackowski S, Smith SH, Tuomanen EI. Bacterial inhibition of phosphatidylcholine synthesis triggers apoptosis in the brain. J Exp Med 200:99-106, 2004.

Xue L, Orihuela CJ, Tuomanen E, Morris S. Defective development and function of follicular, marginal zone, and B1 B cells in Bc110-deficient mice. Nature Immunol 4:855-865,2003.

Weber JR, Freyer D, Alexander C, Schröder NWJ, Reiss A, Küster C, Pfeil D, Tuomanen EI, Schumann RR. Recognition of pneumococcal peptidoglycan: an expanded, pivotal role for LPS binding protein. Immunity 19:269-279, 2003.

Braun JS, Sublett JE, Freyer D, Mitchell TJ, Cleveland JL, Tuomanen EI, Weber JR. Pneumococcal pneumolysin and H2O2 mediate brain cell apoptosis during meningitis. J Clin Invest 109:19-27, 2002.

Zhang J-R, Mostov KE, Lamm ME, Tuomanen E. The polymeric immunoglobulin receptor translocates pneumococci across the human nasopharyngeal epithelial cells. Cell 102:1-20, 2000.

Novak R, Charpentier E, Braun JS, Tuomanen E. Signal transduction by a death signal peptide: uncovering the mechanism of bacterial killing by penicillin. Molec Cell 5:49-57, 2000.

Braun J, Bodner S, Cleveland J, Tuomanen EI. Neuroprotection by a caspase inhibitor in acute bacterial meningitis. Nature Medicine 5:298-302, 1999.

Yoshimura A, Lien E, Ingalls R, Tuomanen E, Dziarski R, Golenbock D. Cutting Edge: Recognition of gram-positive bacterial cell wall components by the innate immune system occurs via toll-like receptor 2. J Immunol 163:1-5, 1999.

Novak R, Henriques B, Charpentier E, Normark S, Tuomanen E. Emergence of vancomycin tolerance in Streptococcus pneumoniae. Nature 399:590-593, 1999.

Ring A, Weiser JN, Tuomanen EI. Pneumococcal trafficking across the blood-brain barrier: molecular analysis of a novel bi-directional pathway. J Clin Invest 1998; 102:347-360, 1998.

Rambukkana A, Salzer JL, Turchenco PD, Tuomanen E. Neural targeting of Mycobacterium leprae mediated by the G domain of the Laminin-α2 chain. Cell 88:811-821, 1997.

Cundell D, Gerard N, Gerard C, Tuomanen E. The platelet activating factor receptor anchors Streptococcus pneumoniae to human cells. Nature 377:435-438, 1995.

Sha W, Liou H, Tuomanen E, Baltimore D. Targeted disruption of the p50 subunit of NF-kB leads to multifocal defects in immune responses. Cell 80:321-330, 1995.

Rozdzinski E, Bharracharyya C, Tuomanen E. Inhibition of leukocyte‑endothelial cell interactions by a bacterial adhesin which mimics coagulation factor X. J Clin Invest 95:1078-1085, 1995.

Spellerberg B, Prasad S, Cabellos C, Tuomanen E. Bacterial disaccharide tetrapeptide induces blood brain barrier permeability. J Exp Med 182:1037-1044, 1995.

Tuomanen E, Prasad S, George J, Hoepelman A, Ibsen P, Heron I. Starzyk R. Reversible opening of the blood brain barrier by antibacterial antibodies. Proc Natl Acad Sci 90:7824-7828, 1993.

Burroughs M, Rozdzinski E, Geelen S, Tuomanen E. A structure-activity relationship for induction of meningeal inflammation by muramyl peptides. J Clin Invest 92:297-302, 1993.

Tuomanen E. Breaching the blood brain barrier. Scientific American 268:80-84, 1993.

Cabellos C, MacIntyre DE, Forrest M, Burroughs M, Prasad S, Tuomanen E. Differing roles for platelet activating factor during inflammation of the lung and subarachnoid space: the special case of Streptococcus pneumoniae. J Clin Invest 90:612-618, 1992.

Saukkonen K, Burnette N, Mar V, Masure R, Tuomanen E. Pertussis toxin contains eukaryotic-like carbohydrate recognition domains. Proc Natl Acad Sci 89:118-122, 1992.

Saukkonen K, Cabellos C, Burroughs M., Prasad S, Tuomanen E. Integrin-mediated localization of Bordetella pertussis within macrophages. J Exp Med 173:1143-1149, 1991.

Tuomanen E, Lindquist S, Sande S, Galleni M, Light K, Gage D, Normark S. Coordinate regulation of beta lactamase induction and peptidoglycan composition by the ampD operon. Science 251:201-203, 1991.

Saukkonen K, Cioffe C, Wolpe S, Sherry B, Cerami A, Tuomanen E. The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis. J Exp Med 171:439-448, 1990.

Relman D, Tuomanen E, Falkow S, Golenbock DT, Saukkonen K, Wright SD. Recognition of a bacterial adhesin by an eukaryotic integrin: CR3 (alpha M beta 2, CD11b/CD18) on human macrophages binds filamentous hemagglutinin of Bordetella pertussis. Cell 61:1375-1382, 1990.

Tuomanen E, Saukkonen K, Sande S, Cioffe C, Wright SD. Reduction of inflammation, tissue damage, and mortality in bacterial meningitis in rabbits treated with monoclonal antibodies against adhesion‑promoting receptors of leukocytes. J Exp Med 170:959‑969, 1989.

Tuomanen E, Liu H, Hengstler B, Zak O, Tomasz A. The induction of meningeal inflammation by components of the pneumococcal cell wall. J Infec Dis 151:859-868, 1985.

Last updated: June 2009

 

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