Dziegielewski Research Interest
Modulating Cellular Responses to Ionizing Radiation
The overall goal of the lab is to advance our understanding of the biological effects of ionizing radiation in hope of developing better sensitizing agents for tumor radiotherapy and protective agents against environmental or occupational radiation exposures.
In the first research area we are exploring the hypothesis that blocking neurotensin receptor 1 (NTR1), or neuroendocrine stimulatory signaling in general, sensitizes prostate cancer cells and tumors to radiotherapy. The NTR1 receptor has been shown to be expressed only in prostate cancer cells, but not in normal prostate. We have demonstrated that a small molecule antagonist of NTR1 selectively and significantly enhances therapeutic effects of radiation in prostate cancer cells in vitro and in vivo, through the mechanism involving EGFR inhibition and apoptosis induction.
A related project (in collaboration with NASA Space Radiation Laboratory, BNL, NY) concentrates on the possible roles of NTR1 expression and neuroendocrine signaling in carcinogenesis of prostate cells exposed to space radiation. Since astronauts are constantly exposed to ionizing radiation from the Sun and the galaxy, better understanding of its biological effects is crucial for future space travel.
In the third research project we are seeking to develop the low voltage-gated calcium channels (LVCCs or T-type) as molecular targets for tumor therapy. We have found that blocking LVCCs induces cell death in glioblastoma tumor cells and sensitizes them to radiotherapy through the inhibition of AKT/mTOR signaling pathways and induction of cell death.