Investigators

Summary

My lab’s cancer research, based on our NCI R01, is to determine if radioprotectants instilled in the urinary bladder prior to irradiation of pelvic or prostate tumors can protect against radiation cystitis without dampening treatment efficacy.  We utilize a mouse model of prostate cancer using orthotopic injections of TRAMPC-1 cells, to which mitochondrial targeted free-radical scavengers are instilled into the bladder using novel infrared guidance method; assuring the instillate enters the bladder and not the prostate.  Fractionated irradiation is used following a single drug installation to determine the duration of bladder protection; important as multiple instillations can lead to urinary tract infections.  As some irradiated tumor cells can become senescent, reestablishing tumorigenicity at a later time, we are also investigating the use of senolytic drugs post radiation therapy.  A potential cause of cell senescence is inhibition of mitophagy where damaged mitochondria cannot be cleared from cells for degradation in lysosomes.  Nitric oxide (NO•) plays a crucial role in both mitochondrial signaling and cell senescence.  We hypothesize that restoring NO•-dependent pathways and increasing cGMP/PKG levels may be beneficial in clearing senescent cells and preventing tumor recurrence and development of treatment resistance.  This one (irradiation) – two (senotherapeutics) punch approach offers the potential to eradicate greater numbers of tumor cells and clear any remaining senescent ones, thus treating tumors and reducing risk of their recurrence.