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.


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).