Current Projects
Current funded and unfunded projects include the following:
NIMBLE: Non-Invasive Markers of Bladder deterioration
R01 DK127673-01A1, in collaboration with Dr. Richard Lee
The goal of this project is to integrate urine and tissue proteomics from human neurogenic bladder patients and a validated, preclinical rodent model of neurogenic bladder following spinal cord injury to identify biomarkers of bladder deterioration. By using urine, which is easily obtainable from patients, we hope to develop a non-invasive screening panel to determine the extent to which the bladder may deteriorate over time in patients with spinal lesions, that could be used in conjunction with urodynamics analysis to optimize patient management.
Targeting PARP signaling as a novel treatment for urologic complications of spinal cord injury
DOD
The goal of this grant is to determine the impact of pharmacological PARP inhibition on functional and molecular outcomes in a rat model of neurogenic bladder dysfunction following spinal cord injury. PARP inhibitors are widely used for treatment of certain cancer types characterized by deficiencies in DNA damage repair. New data from our group implicate DNA damage and PARP activation as drivers of neurogenic bladder pathology following spinal cord injury.
Enhancing botulinum neurotoxin efficacy for neurogenic bladder treatment
DOD, in collaboration with Dr. Min Dong
The goal of this grant is to explore the activity of novel chimeric botulinum toxins in the setting of neurogenic bladder dysfunction following spinal cord injury in a mouse model. Botulinum toxin is used currently in clinical management of patients with neurogenic bladder following spinal cord injury but its effects are not sustained requiring re-injection every 9-12 months. Dr. Dong’s group has developed new versions of botulinum toxin that show higher potency and extended duration of action in preliminary studies in healthy animals. In the proposed studies, we will test the effectiveness of the novel toxins at treating bladder dysfunction that arises following spinal cord injury in mice.
Precision-cut bladder slices: an enabling technology for urologic research
R21 DK138394-01, in collaboration with Dr. Rama Krishnan, BIDMC
The goal of this grant is to develop a novel assay platform comprising precision-cut bladder slices to enable measurement of physiologically relevant endpoints in mouse and human bladder tissue such as contraction, relaxation and stiffness while keeping the native tissue microenvironment intact.
Role of the semaphorin 3F-neuropilin 2 signaling axis in hollow organ contractility
Over the past decade, we have reported a novel role for neuropilin 2 as a regulator of smooth muscle contractility in the bladder and colon. Neuropilins have been most widely studied in the context of axon guidance and angiogenesis, but are also implicated in immune cell function. Our published studies show that bladder or colon tissue from mice with genetic deletion of Nrp2 displayed increased evoked contraction. These results suggest that targeting Nrp2 may represent a novel approach to problems where smooth muscle is poorly contractile such as underactive bladder or colonic dysmotility.