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Candidate: Bryan A. Millis
Program: PhD Biosciences
Date: Thursday November 3, 2011
Time: 10:00 a.m.
Place: George Mason University
Occoquan Bldg., Room 203
Prince William campus
Dissertation Chair: Dr. Serguei Popov
Committee members: Dr. Charles L. Bailey, Dr. Raymond Weinstein, Dr. Taissia Popova
Title: "Induction of Host Extracellular Protein Dysfunction by Bacillus anthracis
Hemolytic Factors"
The dissertation is on reserve in the Johnson Center Library, Fairfax campus.
The doctoral project will not be read at the meeting, but should be read in advance.
All members of the George Mason University community are invited to attend.
ABSTRACT:
Barrier dysfunction represents one of the
most predominant
manifestations of an anthrax infection.
Massive pleural edema, which is classic of inhalational anthrax,
is
perhaps one of the only consistent symptoms among victims of this
pathogen. However, despite much research
into how the pathogen escapes the initial immune response, there
remains little
treatment option at later symptomatic stages of infection. This work demonstrates that a group of
molecules having functions in barrier organization, including
Syndecan-1, are
either shed from the cell surface, or dysfunctional in this role. This dysfunction is co-incident with
manifestations of hemodynamic imbalance, resulting in both accumulation
within
the liver and induction of disseminated intravascular coagulopathy. Further, we suggest specific secreted
virulence factors that contribute to this dysfunction through
acceleration of
host cell shedding processes regulated by MAP kinase
cascades. The mechanism of action of
these virulence factors points toward signaling disturbances which
result not
only in loss of these cell surface molecules, but also cytoskeletal
disorganization and decoupling from adhesion processes.
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