Ph.D. Thesis Defense - Raman Spectroscopy Detects Allograft Rejection with Molecular Specificity
Date: June 18, 2012
Time: 1:00 PM
Location: Bossone Research Enterprise Center, Room: 302
Speaker(s):
Qiang Tu
Advisors: Chang Chang, Ph.D., and Kambiz Pourrezaei, Ph.D.
Details:
Heart transplantation is the last resort therapy for patients with end-stage heart failure and its efficacy relies on the successful management of recipient immune responses. Endomyocardial biopsy is the current standard of care for post-transplantation rejection surveillance of cardiac allografts. Tissue samples are retrieved from the endocardium of the right ventricle with a bioptome. The severity of allograft rejection is graded histopathologically from Grade-0 (no observable rejection) to Grade-3R (most severe), depending on the degree of lymphocyte infiltration and cardiac myocyte damage. Like other biopsy procedures, endomyocardial biopsy is invasive, subject to sampling errors, and causes morbidity and rarely mortality. Its finite turnaround time also incurs unwanted patient anxiety. A less invasive and potentially real-time in vivo diagnostic method is therefore desired.
Optical techniques capable of in vivo and molecularly specific detection of disease markers are continuously being sought after with the goal of replacing invasive biopsy procedures that incur tissue incision and morbidity. Raman spectroscopy, with its chemical and molecular specificity as well as its intrinsic detection capability without the need for exogenous labeling and fixation, presents an attractive opportunity for minimally invasive in vivo diagnostics. Clinical applications of Raman spectroscopy however, have been largely limited by the complexity of tissue constituents in that complicated post-experiment data processing is required and the attainable information is limited to a set of given a priori sample constituents, such as collagen, cholesterol and phospholipids. Use of endogenous biomarkers presents a new paradigm in the medical application of Raman spectroscopy that can potentially overcome such limitations. Here the feasibility of this new paradigm by directly detecting specific biomarkers is examined for disease detection which demonstrates the potential use of Raman spectroscopy as a molecular specific optical biopsy tool for heart transplant rejection surveillance.
The study also corroborates the increasingly recognized role of serotonin receptors in various immune responses including cardiac allograft rejection. Serotonin is both a ubiquitous neurotransmitter in the central nervous system and an important immunomodulator involved in various immune responses. The ability to unambiguously detect serotonin is therefore imperative in biomedical research. However, detection of serotonin and related indoles using immunohistochemistry has been largely limited by their small molecule size and the resultant uncertainty in antibody specificity. Here Surface-enhanced Raman spectroscopy (SERS) is showed to be capable of detecting and distinguishing serotonin from its various closely related precursors and metabolites. Comparing with traditional antibody-based methods, SERS is highly specific and capable of real-time detection. We expect this optical detection method to directly benefit a variety of immune and nervous systems studies involving serotonin.
Biosketch:
Directions:
The Bossone Research Enterprise Center is located at the corner of 32nd and Market Streets.
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