Elaine I. Tuomanen, MD

Member, St. Jude Faculty

Chair, Infectious Diseases Department
Director, Children's Infection Defense Center (CIDC)

Co-Leader, Bacterial Pathogenesis, CIDC

Departments

Education

MD – McGill University, University Scholar

Honors & Awards

2014 Pediatric Infectious Diseases Society Inaugural Distinguished Research Award
2012 Member, Association of American Physicians
2010 Fellow, American Academy for Microbiology
2006 Selected as one of “America’s Top Pediatricians”
1998 Maxwell Finland Award, 36th Infectious Disease Society of America
1997 E. Mead Johnson Award of American Academy of Pediatrics, Outstanding Research in Pediatrics
1987 Outstanding Young Woman of America
1986 Vector Outstanding Young Investigator Research Award, American Society for Microbiology
1983-1986 Parker B. Francis Research Award, The American Thoracic Society
1980 Bristol Award, The American Society for Infectious Diseases
1977 Stewart Prize of Outstanding Overall Competence in Medicine, Candidate, McGill University

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.

Tuomanen Research Lab

Contact Information

Elaine I. Tuomanen, MD Infectious Diseases MS 320, 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

St. Jude Faculty List

News Releases

Selected Publications

Kamei A, Gao G, Neale G, Loh LN, Vogel P, Thomas PG, Tuomanen E, Murray PJ. Exogenous remodeling of lung resident macrophages protects against infectious consequences of bone marrow-suppressive chemotherapy. Proc Natl Acad Sci 113:E6153-61, 2016. PMID 27671632

Kietzman CC, Gao G, Mann B, Myers L, Tuomanen EI. Autolysis Reconsidered: Dynamic Capsule Restructuring by the Pneumococcal Autolysin in Response to the Epithelium. Nature Comm 7:e10859, 2016. PMID 26924467

Humann J, Mann B, Gao G, Moresco P, Ramahi J, Loh LN, Farr A, Hu Y, Durick-Eder K, Fillon SA, Smeyne RJ, Tuomanen EI. Bacterial Peptidoglycan Traverses the Placenta to Induce Neuroproliferation and Aberrant Postnatal Behavior. Cell: Host & Microbe 19:388-399, 2016. PMID 26962947

Mann B, Thornton J, Tweten R, Gao G, El Kasmi K, Heath R, Jordan B, Kriwacki R, Hurwitz J, Tuomanen EI. Broadly protective protein-based pneumococcal vaccine composed of pneumolysin toxoid-CbpA peptide recombinant fusion protein. J Infect Dis 209:1116-25, 2014.

Carter R, Wolf J, van Opijnen T, Muller M, Obert C, Burham C, Mann B, Li Y, Hayden RT, Pestina T, Persons D, Camilli A, Flynn PM*, Tuomanen EI*, Rosch JW*. Genomic analyses of pneumococci from children with sickle cell disease expose host-specific bacterial adaptations and deficits in current interventions. Cell Host Microbe 15:587-99, 2014. (*equal contribution)

Brown A, Mann B, Gao G, Faverio P, Restrepo M, Halade G, Mortensen E, Lindsey M, Hanes M, Happel K, Nelson S, Bagby G, Tuomanen E, Orihuela C. Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function. PLoS Pathog 10(9):e1004383, 2014.

Valentino MD, McGuire AM, Rosch JW, Bispo PJ, Burnham C, Sanfilippo CM, Carter RA, Zegans ME, Beall B, Earl AM, Tuomanen EI, Morris TW, Haas W, Gilmore MS. Unencapsulated Streptococcus pneumoniae from conjunctivitis encode variant traits and belong to a distinct phylogenetic cluster. Nat Commun 12:5411, 2014.

Mann B, van Opijnen, Wang J, Obert C, Wang Y-D, Carter R, McGoldrick DJ, Ridout G, Camilli A, Tuomanen EI, Rosch JW. Control of virulence by small RNAs in Streptococcus pneumoniae. PLoS Pathog 8(7):e1002788. doi:10.1371, 2012.

Garrison SP, Thornton JA, Hacker H, Webby R, Rehg JE, Parganas E, Zambetti GP, Tuomanen EI. The p53-target gene puma drives neutrophil-mediated protection against lethal bacterial sepsis.PLoS Pathog 6(12):e1001240, 2010.

Gaur AH, Bagga B, Barman S, Hayden R, Lamptey A, Hoffman JM, Bhojwani D, Flynn P, Tuomanen E, Webby R. Intravenous Zanamivir for Oseltamivir resistant pandemic A (H1N1) influenza infection.N Engl J Med 362:88-9, 2010.

Rosch JW, Hinojosa E, Pestina T, Hu Y, Boyd AR, Persons DA, Orihuela CJ, Tuomanen EI. Statins protect against lethal pneumococcal infection and cytolysin toxicity in experimental sickle cell disease. J Clin Invest 120:627-35, 2010.

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.

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.

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.

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.

Webby RJ, Perez DR, Coleman JS, Guan Y, Knight JH, Gorvokova EA, McClain-Moss LR, Peiris JS, Rehg JE, Tuomanen EI, Webster RG. Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines. Lancet 363:1099-1103, 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.

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 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 anchorsStreptococcus 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.

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.