Pediatric Basic Science and Clinical Research
The Division of Pediatric Urology maintains a strong investment in basic science and clinical research. We believe laboratory research provides integral insights into caring for children with urinary tract problems and the goal is to identify ways to prevent and/or minimize the morbidity of these disorders. Our clinical research is broad based and centered on both outcomes and translational research from our benches to the bedside.
Basic Science Research
Our basic science research areas of focus include:
- Identifying causes of bladder disease
- Treatments to minimize bladder scarring
The investigative work of our faculty is nationally recognized by multiple organizations, including:
Understanding Bladder Inflammation
Dr. Douglass B. Clayton focuses his basic science research on understanding bladder injury, inflammation, and hypoxic signaling in the urothelium of the bladder. He is funded by the National Institutes of Health through a Mentored Career Development Award from the National Institute of Diabetes and Digestive and Kidney Diseases. He is mentored by Volker H. Haase, MD, Professor of Medicine in the Division of Nephrology and Hypertension.
Dr. Clayton’s research focuses on understanding how the acute activation of the hypoxia inducible factor pathway offers protection in the bladder during injury and inflammation. Numerous urologic conditions are characterized by inflammation including:
- Urinary tract infection
- Bladder stones
- Neurogenic bladder
Small molecule pharmacotherapies are being developed that can selectively activate the hypoxia pathway and allow cells in the bladder to rapidly adapt to environmental stress caused by urologic diseases that injure the bladder. These compounds – called prolyl-4-hydroxylase (PHD) inhibitors – are already available for the treatment of renal anemia and can be repurposed for use in patients with bladder disorders.
The Division of Pediatric Urology is actively studying these compounds to better understand the protective effects of PHD inhibitors in the bladder.
Dr. Clayton’s work is supported by an NIH funded K08 award that lasts five years. Dr. Clayton is one of very few Pediatric Urologists who are awarded this in the country. His work has been presented at numerous scientific meetings, having been nominated for a prize finalist twice.
- Respiratory Heterogeneity Shapes Biofilm Formation and Host Colonization in Uropathogenic Escherichia coli. Beebout CJ, Eberly AR, Werby SH, Reasoner SA, Brannon JR, De S, Fitzgerald MJ, Huggins MM, Clayton DB, Cegelski L, Hadjifrangiskou M. MBio. 2019 Apr 2;10(2)
- F2-isoprostanes as a biomarker of oxidative stress in the mouse bladder. Clayton DB, Stephany HA, Ching CB, Rahman SA, Tanaka ST, Thomas JC, Pope JC 4th, Adams MC, Brock JW 3rd, Clark PE, Hayward SW, Matusik RJ, Milne GL. J Urol. 2014 May;191(5 Suppl):1597-601
- Chronic cyclic bladder over distention up-regulates hypoxia dependent pathways. Stephany HA, Strand DW, Ching CB, Tanaka ST, Milne GL, Cajaiba MM, Thomas JC, Pope JC 4th, Adams MC, Brock JW 3rd, Hayward SW, Matusik RJ, Clayton DB. J Urol. 2013 Oct;190(4 Suppl):1603-9.
Hypoxic Signaling Pathways
Studies underway are trying to determine what happens to bladder cells after and during injury and inflammation. The changes taking place at the cellular level allow cells to adapt and survive.
Hypoxic signaling pathways are one factor related to the cellular adaptive process within the bladder. Hypoxia is a time of reduced oxygen supply within cells or organs. Cells in the body respond to hypoxic periods by activating certain genes that help the cell survive the stress of hypoxia. The process is driven by the Hypoxia Inducible Factor (HIF) pathway.
We now know from studies in other organs that specific proteins in the HIF family are activated during inflammation. These HIF proteins are critical for:
- Activating cells to improve energy production
- Decreasing toxic substances
- Improving overall cell survival
Enzymes called the Prolyl-4-hydroxylase containing domain (PHDs) also regulate HIF proteins. Research from colon and lung studies helps us understand how HIF and PHD proteins reduce inflammation and cell damage during inflammation. We are:
- Testing different available compounds that target PHD enzymes
- Expanding our knowledge of how HIF proteins and PHDs work in the bladder
- Looking for ways to control HIF protein activity before, during and after bladder injury
- Collaborating with investigators in the Department of Nephrology to study the HIF and PHD pathways in more detail using genetic tools and transgenic models
Our current work includes:
- Primary investigator of the NIH-funded Myelomeningocele Trial (MOMS) 1 and 2
- Designated as a Center of Excellence for the Center for Disease Control Spina Bifida Program
- Development of an active and robust oncofertility program for children and teenagers with urologic cancer
- Establishment and maintenance of one of the country’s largest prospective reconstructive urologic surgery database
- Surgical Outcomes for Kids Center (SOCKS)
- The Sacral Neuromodulation Alliance for Pediatric Patients (SNAPP)
- Southeast Pediatric Urologic Research (SPUR)
[H2] MOMS Trial
Our doctors are pioneers in fetal intervention for myelomeningocele. Drs. Tulipan and Bruner completed the first human interventions in 1998. Dr. John Brock, III helped create the protocol that became the MOMS Trial, the only randomized trial comparing pre- and post-natal myelomeningocele closure in the world. This trial included three institutions, including Vanderbilt. Outcomes of this trial are summarized in the papers below, all of which include authors from our division.
- Effect of Prenatal Repair of Myelomeningocele on Urological Outcomes at School Age. Brock JW 3rd, Thomas JC, Baskin LS, Zderic SA, Thom EA, Burrows PK, Lee H, Houtrow AJ, MacPherson C, Adzick NS; Eunice Kennedy Shriver NICHD MOMS Trial Group. J Urol. 2019 May
- Bladder Function After Fetal Surgery for Myelomeningocele. Brock JW 3rd, Carr MC, Adzick NS, Burrows PK, Thomas JC, Thom EA, Howell LJ, Farrell JA, Dabrowiak ME, Farmer DL, Cheng EY, Kropp BP, Caldamone AA, Bulas DI, Tolivaisa S, Baskin LS; MOMS Investigators. Pediatrics. 2015 Oct;136(4)
- A randomized trial of prenatal versus postnatal repair of myelomeningocele. Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D'Alton ME, Farmer DL; MOMS Investigators. N Engl J Med. 2011 Mar 17;364(11):993-1004.
CDC Spina Bifida Program
Dr. Stacy Tanaka serves as principle investigator for two Centers for Disease Control and Prevention spina bifida grants:
The National Spina Bifida Patient Registry is a multi-center study to collect data on patient demographics, treatment and outcomes in order to better understand the associations between medical procedures and health outcomes.
- Design and methodological considerations of the National Spina Bifida Patient Registry Urologic and Renal Protocol for the newborn and young child. Routh JC, Cheng EY, Austin JC, Baum MA, Gargollo PC, Grady RW, Herron AR, Kim SS, King SJ, Koh CJ, Paramsothy P, Raman L, Schechter MS, Smith KA, Tanaka ST, Thibadeau JK, Walker WO, Wallis MC, Wiener JS, Joseph DB. J Urol 196(6): 1728-1734, 2016.
- Bowel management and continence in adults with spina bifida: results from the National Spina Bifida Registry 2009-2015. Wiener J, Suson KD, Castillo J, Routh JC, Tanaka S, Liu T, Ward E, Thibadeau J, Joseph D, Registry NSBP. J Pediatr Reabil Med 10(3-4): 335-343, 2017. [PMID: 29125526]
- Bladder management and continence outcomes in adults with spina bifida: results from the National Spina Bifida Registry 2009 to 2015. Wiener JS, Suson KD, Castillo J, Routh JC, Tanaka S, Liu T, Ward E, Thibadeau J, Joseph D; National Spina Bifida Registry. J Urol 200(1): 187-194, 2018. [PMID: 29588216]
The Urologic Management to Preserve Initial Renal Function Protocol for Young Children with Spina Bifida (UMPIRE) works to develop a protocol that will safely and effectively monitor how well the bladder and kidneys are working in newborns and young children with spina bifida.
- Baseline Urinary Tract Imaging in Infants Enrolled in the UMPIRE Protocol for Children with Spina Bifida. Tanaka ST, Paramsothy P, Thibadeau J, Wiener JS, Joseph DB, Cheng EY, Tu D, Austin C, Koh CJ, Wallis MC, Walker WO, Smith KA, Routh JC, Baum MA. J Urol. 2019 Jun;201(6):1193-1198
Our newest faculty member, Dr Abby Taylor [link to Profile] is interested in clinical outcomes research. She is pursuing a Masters of Public Health with an emphasis in Biostatistics. Dr. Taylor is spearheading our efforts in close collaboration with Pediatric Hematology/Oncology/Endocrinology to create a combined oncofertility program. This allows us to counsel patients about fertility risks and educate them about how to bank germ cells for future use prior to chemotherapy and/or radiation.
Reconstructive urologic surgery database
Drs. Mark Adams and John Thomas have overseen the development of a robust prospective database of children who have undergone major urologic bladder reconstruction. This database was initially built by one of our former residents, Dr. Debbie Jacobson, who is currently a Pediatric Urologist in Utah. The database has grown to almost 100 patients and was recently updated by Dr. Cyrus Adams also a former Vanderbilt resident and current Pediatric Urology fellow at Indiana University. This database captures every adverse event following reconstruction. Outcomes have been reported at National conferences and published in peer reviewed journals.
[H3] Selected Publications
- Update on Continent Catheterizable Channels and the Timing of their Complications. Jacobson DL, Thomas JC, Pope J 4th, Tanaka ST, Clayton DB, Brock JW 3rd, Adams MC.J Urol. 2017 Mar;197(3 Pt 2):871-876.
A major contributor to our clinical outcomes and research success is the SOCKS (Surgical Outcomes for Kids) Center under the direction of Dr. Chevis Shannon. Our faculty, fellows and residents collaborate with SOCKS and Dr. Shannon’s team to create clinical projects assessing outcomes in our patients.
We present these studies at national meetings and publish our findings in peer-reviewed journals. SOCKS is instrumental in helping our urology team get IRB approval, organize data, implement pathways, and perform statistical analysis. To date, we have collaborated on 59 different projects.
[H2] The Sacral Neuromodulation Alliance for Pediatric Patients (SNAPP)
Sacral neuromodulation has been shown to be successful in some patients with refractory voiding dysfunction. Dr. John Pope, IV is the only pediatric urologist in Tennessee who is implementing this technology in pediatric patients. He has one of the largest experiences in the Southeast and is invited to share his experience at national meetings. Dr. Pope and colleagues have created a multi-institutional consortium (SNAPP) to track outcomes and standardize the evaluation, placement, and post-procedural management in this patient population.
Southeast Pediatric Urologic Research (SPUR)
Spearheaded this year by Dr. John C. Pope, IV, this alliance includes four institutions in the southeast that will come together and share ideas for research endeavors. We are looking forward to this collaborative effort with our pediatric urologic colleagues that will focus on better outcomes for the children and families we serve.