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.
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
The doctoral project will not be read at the meeting, but should be read
All members of the George Mason University community are invited to attend.
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).