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My laboratory studies urinary bladder dysfunctions due to benign prostatic hyperplasia and obstruction (BPH and BPO), radiation cystitis and spinal cord injury (SCI), their pathological development and new therapeutic options. We use cutting edge approaches including telemetric bladder pressure and sphincter activity recordings in freely mobile rodents to diagnose and characterize BPH-induced BPO, and SCI-induced detrusor-sphincter dyssynergia (DSD) where the urethral sphincter and bladder contract together causing outlet obstruction. We also study neurogenic and myogenic bladder overactivity as a cause of incontinence, using optical mapping of voltage and calcium transients in bladder sheets, genetically encoded fluorescent probes and targeted drug delivery in normal, pathological, and genetically modified rodents.
We were first to demonstrate naturally occurring BPO in aged rodents and its’ alleviation with soluble guanylate cyclase (sGC) activators that stimulate cGMP production by nitric oxide-insensitive oxidized sGC. We were also first to directly measure nitric oxide production by bladder urothelial cells using porphyrinic microsensors and utilize mitochondrial targeting of free radical scavengers to protect the bladder when administered prior to irradiation insult—this work won the ASPET-Astellas award in translational pharmacology and contributed to two United States Patents. We have also demonstrated the therapeutic benefits of pro-apoptotic p75 neurotrophin receptor inhibitors and pro-growth TrkA/B stimulators in reversing DSD and reducing contused spinal cord glial/collagen scaring to improve hindlimb mobility, respectively.
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