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Brian Akerley, Ph.D.
Academic Role: Assistant Professor
Faculty Appointment(s) In:
Molecular Genetics and Microbiology
Biology and pathogenicity of Haemophilus influenzae
Research in the Akerley lab focuses on the biology and pathogenicity of Haemophilus influenzae, a bacterium that colonizes humans and leads to disease by spreading from the nasopharyngeal mucosal epithelium to other sites in the body. Depending on a complex interplay between the host and the infectious strain, H. influenzae invades the bloodstream, spreads to the middle ear, infects the lungs, or colonizes the nasopharynx persistently without producing symptoms. The transition between asymptomatic colonization and disease involves a change in the balance between bacterial virulence mechanisms and host defenses. Understanding how this balance is maintained and disrupted will require a comprehensive understanding of H. influenzae biology within the host, its only known growth environment in nature.
Since the complete DNA sequences of the genomes of H. influenzae and those of many other bacteria have been determined, powerful genome-scale approaches to microbiology have become available. Our work incorporates these current methodologies and we have also devised several new genome-based approaches for our studies of H. influenzae. We are currently applying these approaches to other bacterial pathogens. We expect that insights obtained and technology developed in our studies of H. influenzae will enhance understanding of diverse bacterial pathogens.
Selected Publications
Gawronski, J.D., Wong, S.M.S., Giannoukos, G., Ward, D.V., and B. J. Akerley. Tracking insertion mutants within libraries by deep sequencing and a genome-wide screen for Haemophilus genes required in the lung. PNAS 2009 September 22: 106: (38) 16422-16427 [ PDF article ] [PNAS Article]
Harrington JC, Wong SM, Rosadini CV, Garifulin O, Boyartchuk V, Akerley BJ. Resistance of Haemophilus influenzae to reactive nitrogen donors and gamma interferon-stimulated macrophages requires the formate-dependent nitrite reductase regulator-activated ytfE gene. Infect Immun. 2009 May;77(5):1945-58. Epub 2009 Mar 16. PMID: 19289513; PMCID: PMC2681730.
Wong, S.M. and B.J. Akerley. (2008) Identification and analysis of essential genes in Haemophilus influenzae. In S.Y. Gerdes and A.L. Osterman (eds.) Gene Essentiality at the Genomic Scale: Protocols and Bioinformatics. Humana Press. Methods Mol Biol. 416:27-44.
Rosadini, C., Wong, S.M., and B. J. Akerley. (2008). The periplasmic disulfide oxidoreductase DsbA contributes to Haemophilus influenzae pathogenesis. Infect. Immun. Apr;76(4):1498-508.
Vijayalakshmi, J., Akerley, B.J., and M.A. Saper. (2008). Structure of YraM, a protein essential for growth of Haemophilus influenzae. Proteins. Proteins 73:1, 204-217. PMID: 18412262.
Wong, S.M., Alugupalli, K., Ram, S., and B.J. Akerley. (2007) The ArcA regulon and oxidative stress resistance in Haemophilus influenzae . Molecular Microbiololgy 64(5):1375-90.
Wong, S.M. and B.J. Akerley. (2005) Environmental and genetic regulation of the phosphorylcholine epitope of H. influenzae . Molecular Microbiology 55(3):724-38.
Raghunathan, A., Price, N.D., Galperin, M.Y., Makarova, K.S., Purvine, S., Picone, A.F., Cherny, T., Xie, T., Reilly, T.J., Munson, R., Jr., Tyler, R.E., Akerley, B.J., Smith, A.L., Palsson, B.O., Kolker, E. (2004) In Silico Metabolic Model and Protein Expression of Haemophilus influenzae Strain Rd KW20 in Rich Medium. OMICS. 8(1):25-41.
Bergman, N. H. and B.J. Akerley. (2003) Position-Based Scanning for Comparative Genomics and Identification of Genetic Islands in Haemophilus influenzae Type b. Infect. Immun. 71:1098-1108.
Wong, S. M. and B.J. Akerley. (2003) Inducible expression system and marker-linked mutagenesis approach for functional genomics of Haemophilus influenzae . Gene 316:177-186.
Akerley, B.J., Rubin, E. J., Novick, V. L., Amaya, K., Judson, N., and J. J. Mekalanos. (2002) A Genome-Scale Analysis of Genes Required for Growth or Survival of Haemophilus influenzae . Proc. Natl. Acad. Sci. U.S.A 99:966-971.
Akerley, B. J. and D. J. Lampe. (2002) Analysis of Gene Function in Bacterial Pathogens by GAMBIT. In V. L. Clark and P. M. Bavoil (eds.) Methods in Bacterial Pathogenesis Part C. Meth. Enzymol. 358:100-108.
Georgellis, D., Kwon, O., Lin, E.C.C., Wong, S.M., and B.J. Akerley. (2001) Redox Signal Transduction by the ArcB Sensor Kinase of Haemophilus influenzae lacking the PAS domain J. Bacteriol. 183(24):7206-7212.
Rotations
H. influenzae and other bacterial pathogens encounter and respond to diverse microenvironments within their hosts. H. influenzae is highly adapted to the human respiratory tract and and can persist despite active immune responses against its surface constituents. We have found virulence genes of H. influenzae that are subject to modulation in response to environmental conditions, providing potential mechanisms for avoiding host defenses and optimizing colonization. Rotation projects utilize genetic methodologies we have devised in the lab or adapted for use in H. influenzae to analyze bacterial signal transduction and physiological adaptations important during infection of model hosts. Another area of interest is the application of genome-scale technology and conceptual frameworks developed in our studies of H. influenzae to other pathogens. Students will receive training in bacterial genetics and pathogenesis in addition to an introduction to genome-scale approaches of molecular biology.
Academic Background
1995: PhD in Microbiology and Immunology from UCLA School of Medicine
1996: Damon Runyon-Winchell postdoctoral fellowship, Harvard Medical School, www.damonrunyon.org
1999: Instructor in Microbiology, Harvard Medical School
1999: Assistant Professor of Microbiology and Immunology, University of Michigan Medical School
2000: Dade Microscan Young Investigator Award, http://newsarchive.asm.org/feb01/news.asp
2003: Assistant Professor of Molecular Genetics and Microbiology, UMASS Medical School
Phone: 508-856-1442
E-mail: Brian.Akerley@umassmed.edu
Keywords:
Genetic Systems,
Infectious Disease,
Microbial Pathogenesis
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