My laboratory is interested in understanding the complexities of urinary bladder epithelial (urothelial) cell function and urothelial cell-neuronal interactions. Our investigations have revealed that the urothelium, a stratified epithelial layer that lines the bladder lumen, might have the capacity to send signals to neighboring cells via the release of chemical mediators. Our identification of a number of functional receptors/ion channels in bladder urothelial cells and the possible involvement of these receptors/ion channels in the release of mediators suggest that these cells exhibit specialized sensory and signaling properties. This arrangement would represent a departure from the conventional view of the urothelium as a simple barrier and provide further support for our speculation that the urothelium has “neuron-like” properties and that it may play a role in sensory mechanisms in the urinary bladder. Through an array of experimental approaches that include molecular biology (mouse knockouts; qRT-PCR, western blot; quantitative morphology), functional assays (measurement of transmitters; mitochondrial function; Ca2+/confocal imaging; in vivo assessment of bladder function and pain behavior), our goals are to further characterize the properties of urothelial cells. Elucidation of mechanisms impacting on urothelial function in addition to how pathology may impact on mechanisms of urothelial communication may provide important insight into targets for new therapies for the clinical management of lower urinary tract disorders.

It has been demonstrated that there are multiple intercellular signaling mechanisms that occur within the urinary bladder wall to modulate sensory outflow and thus affect storage and voiding function. Alterations in bladder sensory function have been attributed to a number of pathologies including, interstitial cystitis, and overactive and underactive bladder syndromes. There is limited number of therapeutic options for these conditions and further understanding of bladder sensory regulation is necessary to elucidate new treatment modalities.

Our lab has demonstrated communication of urothelial cells with lamina propria pacemaker interstitial cell. In certain pathologies, bladder interstitial cells become interconnected by gap junctions. This permits interactions with the detrusor smooth muscle to enhance autonomous bladder contractions and stimulation sensory nerves responsible for initiating micturition; therefore contributing to overactive bladder symptoms. Our research has now expanded to also examine the interaction of sensory nerves with interstitial cells and the bidirectional communication between sensory neurons and the urothelium.

The overall goal of our research is to characterize the intrinsic communication mechanisms between the different layers of the bladder wall and determine their role in lower urinary tract dysfunction.