The Hasan Program Project
Physical and Biological Determinants for Optimal PDT
Norman S. Nishioka, M.D.
Associate Professor of Dermatology, Harvard Medical School
Phone: 617-726-8409
Fax: 617-726-4103
E-mail: nnishioka@partners.org
Complete curriculum vitae is available in text format.
Positions held
- 1981. M.D., University of California, Los Angeles
- 1981-1984. Resident in Medicine, Massachusetts General Hospital
- 1984-1987. Research Fellow in Medicine, Harvard Medical School
- 1984-1987. Clinical and Research Fellow in Medicine, Gastrointestinal Unit, Massachusetts General Hospital
- 1987. Assistant in Medicine, Massachusetts General Hospital
- 1987. Instructor in Medicine, Harvard Medical School
- 1988. Assistant Professor of Medicine, Harvard Medical School
- 1989. Assistant Professor, Division of Health Sciences and Technology, Massachusetts Institute of Technology
- 1992, Assistant Physician, Massachusetts General Hospital
- 1997-. Associate Physician, Massachusetts General Hospital
- 1999-. Associate Professor of Medicine, Harvard Medical School
Role and rationale in PPG
Leader of Project 2
Project 2 aims at improving the treatment of dysplastic Barrett's esophagus (BE) using ALA-PDT and strategies for enhancing PDT. The study is designed around a single randomized controlled trial that will evaluate the interdependence of retinoid therapy and fluence rate or light fractionation on ALA-PDT of Barrett's patients. Firstly, the concept of target cell modification (differentiation) will be applied by pretreating patients with 13-cis retinoic acid in order to enhance PS selectivity to the target tissue by modulating the rate of PPIX formation in dysplastic cells. Retinoids may modulate the selective accumulation of ALA-induced PPIX in esophageal mucosa by influencing the expression or activity of heme forming enzymes. Recently, human and animal studies have examined the selective mucosal activities of the porphyrin-forming enzyme porphobilinogen deaminase (PBGH) and the porphyrin-converting enzyme ferrochelatase (FCH). Higher ratios of PBGD: FCH may increase porphyrin accumulation. Studies in cancer cells have indicated that PBGD may be inducible by ALA exposure. The experiments described in this proposal will simultaneously measure the in vivo expression of these three enzymes in BE and the effect that differentiation therapy has on their expression in collaboration with Project 1. In addition, the effectiveness of differentiation therapy on clinical outcome of Barrett's patients following ALA-PDT will be assessed in a randomized clinical trial. The second way of enhancing PDT is by modifying light delivery regimens. Varying the fluence rate and fractionating the incident light are potential methods for improving PDT. PS produce tumor toxicity primarily through the formation of oxygen radicals. Consequently, oxygen is consumed at high rates during PDT. Increasing the fluence rate of incident light during PDT generally results in decreasing treatment efficacy presumably due to transient PDT-induced hypoxia. The effectiveness of varying fluence rate and light fractionation on clinical outcome will be assessed with and without retinoid therapy. The effects of light fractionation on ALA-PDT in humans have not been studied. In collaboration with Project 3, early optical diagnostic parameters will be measured and correlated to long-term treatment outcome. The diagnostic parameters include the photobleaching rate of PS, the accumulation and subsequent photobleaching rates of PPd, and the changes in tissue reflectivity during PDT. The measurement of these parameters requires the development of an in vivo dosimeter system, which will apply the combined skills of Project 2 and 3 investigators.
Major research interests
The research interests of Dr. Nishioka are primarily focused on the development of novel clinical applications of light and studies of the interactions of light with tissue. A primary interest is using lasers to probe tissue for diagnostic purposes. These investigations utilize spectroscopic techniques that have been adapted for use in vivo. Examples of clinical applications are the identification of gastrointestinal neoplasia and dysplasia. Dr. Nishioka is also utilizing optical technology to improve the accuracy of gastrointestinal endoscopy procedures. Examples of these investigations include the use of real-time digital image processing and low coherence optical imaging. He has several patents related to these research endeavors.
Dr. Nishioka is also interested in the laser ablation of tissue. Much of the research on laser ablation of biological tissues has focused on the mechanisms by which pulsed lasers interact with tissue. This area of investigation is important because understanding the physical processes by which lasers ablate materials can enable the development of new medical applications of lasers and can provide insight into how existing applications can be optimized. Dr. Nishioka's research in this area has led to many new insights into the ablation process, has enabled the development of numerous new laser procedures and has influenced the design of many commercial medical laser instruments.
In his laboratory, Dr. Nishioka supervises undergraduate, graduate, medical and post-graduate students and fellows. He is also an attending physician in the gastrointestinal endoscopy unit and on the gastroenterology consultation and general medical services. As a member of the Board of Advisors in the Division of Health Sciences and Technology at Massachusetts Institute of Technology he advises 15 medical students. He was the first gastroenterologist to perform photodynamic therapy in New England and is an active clinical investigator in this area. He is the Director of Research for the Partners Center for Innovative Minimally Invasive Therapy and Clinical Director of the MGH Laser Center.