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Michael J. Federle, Ph.D.Jimmy Orjala

Assistant Professor
Departmenf of Medicinal Chemistry and Pharmacognosy

University of Illinois at Chicago
Molecular Biology Research Building
900 South Ashland (M/C 870)
Chicago IL 60607-7173

Office: 3152 MBRB
Office Phone: 312-413-0213
Lab Phone:
Fax Number: 312-413-9303
E-mail address: mfederle@uic.edu
Website: http://www.uic.edu/labs/federle/

Education:

University of Wisconsin-Madison, BS (Genetics), 1994
Emory University, Ph. D (Microbiology and Molecular Genetics), 2002
Princeton University/Howard Hughes Medical Institute, Postdoctoral Research Fellow (Molecular Biology), 2008

Research Interests:

We are focused on understanding how bacteria coordinate gene expression across a population using cell-to-cell communication. Many important behaviors and activities of bacteria, including the ability to become virulent, to form biofilms, or to enter the competent state, are controlled through intercellular communication. This process, referred to as quorum sensing, facilitates inter-bacterial communication and the ability to communicate between bacteria and host, thus potentially affecting the health of the host. Intercellular communication relies on secreted signaling molecules (which we refer to as pheromones) that are detected by various types of receptor proteins in recipient cells. Pheromone detection potentiates differential gene expression.

We have identified and characterized new quorum sensing pathways in Streptococcal species. The protein family known as Rgg is central to these signaling pathways, dually acting as cytoplasmic receptors of peptide pheromones and transcriptional regulators. Rgg proteins contribute to a complex quorum-sensing network in Streptococcus pyogenes (Group A Streptococcus, or GAS). GAS is responsible for a wide variety of diseases that range in severity from mild cases of impetigo and pharyngitis (strep throat), to life-threatening necrotizing fasciitis, myonecrosis, and toxic shock. Acute rheumatic fever and rheumatic heart disease are a leading cause of death from streptococcal infections in developing countries. We are currently investigating the molecular nature of the streptococcal quorum sensing network, and its role in controlling virulence factors that contribute to disease. Our studies will lead to the development of new methodologies that disrupt infectious diseases by interfering with bacteria's ability to coordinate their assault on the human body.

 

Select Publications:

  1. Chang, J.C., B. LaSarre, J.C. Jimenez, C. Aggarwal, and M.J. Federle. Two Group A Streptococcal
    Peptide Pheromones Act Through Opposing Rgg Regulators to Control Biofilm Development. PLoS
    Pathog. 7(8): e1002190. doi:10.1371/journal.ppat.1002190.
  2. LaSarre, B. and M.J. Federle. 2011. Regulation and Consequence of Serine Catabolism in
    Streptococcus pyogenes. Journal of Bacteriology. 193(8): 2002-2012.
  3. Mashburn-Warren, L., D.A. Morrison, and M.J. Federle. 2010. A novel double-tryptophan peptide
    pheromone controls competence in Streptococcus spp. via an Rgg regulator. Mol Microbiol,
    78(3):589-606. PMID: 20969646. This article was featured in a MicroCommentary in same issue.
  4. Federle, Michael J. 2009. Autoinducer-2 Based Chemical Communication in Bacteria: Complexities
    of Interspecies Signaling. In Bacterial Sensing and Signaling, Editors Raymond Schuch and Mattias
    Collin. Karger Publishing. 16:18-32.
  5. Neiditch*, M.B., M.J. Federle*, A.J. Pompeani, R.C. Kelly, D.L. Swem, P.D. Jeffrey, B.L. Bassler, and
    F.M. Hughson. 2006. Autoinducer-2-induced asymmetry regulates LuxPQ quorum Sensing signal
    transduction. Cell. 126(6):1095-108. *Authors contributed equally to work.
  6. Neiditch, M.B., M.J. Federle, S.T. Miller, B.L. Bassler, F.M. Hughson. 2005. Regulation of LuxPQ
    receptor activity by the quorum sensing signal autoinducer-2. Molecular Cell. 18(5):507-18.
  7. Semmelhack, M.F., S.R. Campagna, M.J. Federle, and B.L. Bassler. 2005. An Expeditious
    Synthesis of DPD and Boron Binding Studies. Organic Letters. 7(4):569-72.
  8. Semmelhack, M.F., S.R. Campagna, C. Hwa, M.J.Federle, and B.L. Bassler. 2004. Boron binding
    with the quorum sensing signal AI-2 and analogues. Organic Letters. 6(15):2635-7.
  9. Federle, M.J. and B.L. Bassler. 2003. Interspecies communication in bacteria. Journal of Clinical
    Investigation. 112(9):1291-1299.
  10. Federle, M. J. and J.R. Scott. 2002. Identification of binding sites for the group A streptococcal global
    regulator CovR. Molecular Microbiology. 43(5), 1161-72.
  11. Graham, M.R., L.M. Smoot, C.A. Migliaccio, K. Virtaneva, D.E. Sturdevant, S.T. Porcella, M. J.
    Federle, G.J. Adams, J.R. Scott, and J.M. Musser. 2002. Virulence control in group A Streptococcus by
    a two-component gene regulatory system: global expression profiling and in vivo infection modeling.
    Proc. Nal. Acad. Sci. USA. 99(21):13855-13860.
  12. Benfang, L., F.R. Deleo, N.P. Hoe, M.R. Graham, S.M. Mackie, R.L. Cole, M. Liu, H.R. Hill, D. E.
    Low, M. J. Federle, J.R. Scott, and J.M. Musser. 2001. Evasion of human innate and acquired immunity
    by a bacterial homologue of CD11b that inhibits opsonophagocytosis. Nature Medicine. 7(12):1298-
    1305.
  13. Federle, M.J., K.S. McIver, and J.R. Scott. 1999. A response regulator that represses the
    transcription of several virulence operons in the group A Streptococcus. Journal of Bacteriology.
    181:3649-3657.
  14. Eichenbaum, Z., M.J. Federle, D. Marra, W.M. DeVos, O.P. Kuipers, M. Kleerebezem, and J. R.
    Scott. 1998. Use of the lactococcal nisA promoter to regulate gene expression in gram-positive bacteria:
    comparison of induction level and promoter strength. Applied and Environmental Microbiology. 64:
    2763-2769.


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