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Elaine I. Tuomanen, MD
Elaine I. Tuomanen, MD

Elaine I. Tuomanen, MD

Member, St. Jude Faculty

Departments

Education

MD – McGill University, University Scholar

Honors & Awards

  • 2021 Pediatric Infectious Diseases Society Award of Excellence for Outstanding Commitment and Leadership 
  • 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.

Selected Publications

Mann B, Crawford J, Reddy K, Lott J, Youn YH, Gao G, Guy C, Chou C-H, Bomme P, Loughran A, Thomas P, Han YG, Tuomanen EI. Bacterial TLR2/6 Ligands Block Ciliogenesis, Derepress Hedgehog Signaling, and Expand the Neocortex. mBio Jun 27;14(3):e0051023, 2023. PMID: 37052506

MacCain W, Tuomanen E. Taste vs pain: a sensory feast in bacterial meningitis. Cell Host & Microbe 31:681-682, 2023. PMID: 37167946

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.

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.

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.

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.

Last update: August 2023

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