Theresa M. Busch, Ph.D.
Assistant Professor
(215) 573-3168 (office)
(215) 573-6403 (lab)
buschtm@mail.med.upenn.edu
Research Interests
Our primary research focus is the investigation of photodynamic therapy (PDT) for the treatment of solid malignancies. PDT involves the local illumination of tumors that have accumulated a photosensitizer following exogenous administration of the photosensitizer or its precursor. The light-excited photosensitizer interacts with oxygen in the treated tissues (tumor) to produce reactive oxygen species that damage the tissue and its associated stroma, including the supporting vascular network. Insomuch as oxygen is a substrate in the photochemical reactions initiated by PDT, it is both required for and consumed by PDT. However, in addition to oxygen consumption by the photochemical process, impairment of oxygen delivery through PDT-created vascular damage, or the simultaneous occurrence of both of these processes can lead to the development of response-limiting hypoxia during therapy. Our research is centered on defining the intratumor and intertumor distributions of microenvironmental factors essential to PDT, such as oxygenation, vascularization, perfusion, and photosensitizer concentration, toward the goal of identifying approaches to improve PDT response through manipulation of microenvironmental targets or physiological processes.
Our studies have found that PDT can create widespread, severe hypoxia during illumination, even in tumor cells immediately adjacent to perfused tumor vasculature. These data represent the first in vivo demonstration of PDT effect on the spatial distribution of tumor oxygenation and perfusion. Our investigations of tumor oxygen and photosensitizer concentrations extend to the clinic, where PDT offers the advantage of being suitable for patients previously treated with ionizing radiation or chemotherapy. In the largest study to date on photosensitizer uptake in the tissue of patients scheduled to receive PDT, we have measured the concentration of photosensitizer in peritoneal malignancies of several histologies, as well as in relevant normal tissues. Results from this study, as well as our other clinical investigations, have provided direction for our continuing preclinical efforts in defining approaches to modulate tumor microenvironment so as to improve the therapeutic index and long-term efficacy of PDT.
Busch Lab
- Theresa Busch, Ph.D.
- Elizabeth Rickter, M.S.
- Shirron Carter, B.S.
- Min Yuan, M.D.
- Amanda Maas (B.S. candidate, University of Pennsylvania)
- David Warmflash, M.D.
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