Areas of Research
Calcium Microfluorimetry of Human Bladder Urothelial CellsThe role that bladder urothelial cells (BUC) modulate bladder function (continence and micturition) is relatively unknown at this point. Traditionally, the function of BUC have been thought of as only providing a protective role (as in any epithelium) to the underlying bladder stroma from urinary toxins/irritants. The primary determinant of bladder function has always been presented in the “neuromuscular” framework (afferent nerve provide bladder sensation, efferent nerve causes bladder smooth muscle to contract). However, this paradigm has been shifting and the proposed role of BUC now includes modulation afferent signaling of the bladder which ultimately impacts bladder continence and micturition mechanisms. Because the BUC express neurotransmitter receptors (such as purinergic receptors, muscarinic receptors, nicotinic receptors, TRP-receptors) and the BUC release neurotransmitters (such as acetylcholine, nitric oxide, ATP), BUC have a “sensor and transducer” function (as coined by Dr. Lori Birder from University of Pittsburgh). The sensor-transducer role of BUC puts the bladder urothelium front and center as a possible target in continence disorders such as idiopathic overactive bladder (OAB). We have been studying BUC sensor-transducer physiology, and specifically BUC obtained from human OAB subjects (and also asymptomatic human subjects). The video shows how human BUC can respond to a neurotransmitter (carbachol) in a dose-dependent manner. The cellular response being shown by the video is increasing fluorescence which reflect increasing intracellular calcium concentrations with increasing carbachol. Furthermore this response was augmented in OAB BUC compared to asymptomatic controls). This video is an experiment called calcium microfluorimetry. Our laboratory is on the vanguard in studying human BUC in this manner. Any animal models studying BUC function should be informed by human BUC studies, increasing translational relevance. Our laboratory seeks to be translationally relevant in order to effect a change in clinical urology in a more efficient and scientifically relevant manner.
MR-US Image Fusion for Targeted Prostate BiopsyProstate cancer is the most common form of malignant carcinoma and is the second leading cause of cancer-related death in men. Screening methods such as PSA has recently come under fire due to issues with specificity and the generation of false positives and overtreatment of cancers. Furthermore, traditional prostate biopsy techniques, even ultrasound guided, are taken “blind” to sites of cancer. Other imaging modalities have shown promise in the detection of nodules before metastasis, but lack clinical acceptance.
Immunohistochemical analysis of biomarker expression (green) in normal and malignant prostate. (Image on Left side is Normal)