Dissertation Defense Announcement
To: The George Mason University Community
Candidate: Michelle Raiszadeh
Program: PhD Biosciences
Date: Friday April 27, 2012
Time: 3:00 p.m.
Place: George Mason University
Bull Run Hall #246
Prince
William campus
Dissertation Director: Dr. Lance Liotta
Committee members: Dr. Emanuel Petricoin III, Dr. John Schreifels, Dr.
Paul Russo
Title: "Proteomic Analysis of Eccrine Sweat: Implications for the
Discovery of Schizophrenia Biomarker Proteins"
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:
Although efforts have been made for over 20 years, there is currently
no physical, clinical test available to confirm or diagnose
schizophrenia (SZ). For now, psychiatrists must rely on diagnosis
based on clinical symptoms. This requires an evaluation that takes
several hours to perform. No single symptom is definitive for
diagnosis. Instead, the diagnosis encompasses a pattern of signs and
symptoms, along with impaired occupational or social functioning in
accordance with the Diagnostic and Statistical Manual of Mental
Disorders DSM-IV-TR. Even with a thorough psychiatric evaluation, SZ
is often misdiagnosed as Schizoid Personality, Schizophreniform
Disorder, Schizotypal Personality, Bipolar Disorder (Manic Depression)
which is also frequently misdiagnosed as SZ, and Asperger's Syndrome.
For this reason, many patients are prescribed medications for the wrong
illness leading to exacerbation of the symptoms that they already have
and possibly the addition of more symptoms that did not already exist.
Current and past research efforts to produce a physical diagnostic test
for SZ have focused on fluids such as blood and cerebral spinal fluid,
both requiring invasive procedures for collection. One fluid that has
yet to be explored widely for potential diagnostic biomarkers is
sweat. This fluid has been found to be a rich source of novel proteins
that are also found to be differentiated in SZ patient sweat, and,
thus, may hold the key for the first non-invasive, diagnostic test for
SZ and pave the way for other non-invasive clinical diagnostic tests.
This dissertation describes the first ever, large-scale study of the
eccrine sweat proteome which has been shown to have a vast population
of proteins and peptides including those found to be differentiated in
SZ versus controls. This research focuses on the sweat proteome of
those diagnosed with SZ and age-, race-, and gender-matched, healthy
controls. Differentiated proteins, as well as proteins found in both
patients and controls at similar levels, were determined through
analytical methods. Liquid chromatography tandem mass spectrometry
(LC-MS/MS) and multiple reaction monitoring mass spectrometry (MRM-MS)
proteomics analyses were performed on eccrine sweat of healthy
controls, and the results were compared with those from individuals
diagnosed with SZ. Seventeen proteins showed a differential abundance
of approximately two-fold or greater between the SZ sample pool and the
control sample pool. This research demonstrates the utility of
LC-MS/MS and MRM-MS as a viable strategy for the discovery and
verification of potential sweat protein disease biomarkers. This
dissertation also includes a study to evaluate the reproducibility of
eccrine sweat samples collected using the Webster sweat inducer and the
MacroductTM sweat collector and relationships between SZ and selected
proteins that were found to be differentially abundant between patients
and controls. These relationships were determined using the Database
for Annotation, Visualization, and Integrated Discovery and the first
schizophrenia molecular network (SMN) (Sun et al. 2010).
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