Weill Cornell Medicine Urology
Weill Cornell Medicine Urology
The Institute for Pediatric Urology Research Lab

The Institute for Pediatric Urology Research Lab

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Clinical

We are the first and only Center of Excellence for patients with Congenital Adrenal Hyperplasia (CAH). We are a main referral site for pediatric and adult patients with CAH and provide our patients with specialized care through a comprehensive team of clinicians. In addition, Dr. Poppas and colleagues have over 20 years of experience in all areas of pediatric urologic surgery. This allows us to be at the forefront of clinical research in both CAH and in pediatric surgical outcomes research. Under the leadership of Dr. Poppas and Research Coordinator, Kerlly Bernabé, clinicians train in the following areas: the development of databases and research plans, interpretation of data analysis and drafting manuscripts for peer-reviewed journals.

Our institute is participating in the first-ever multicenter study of surgical outcomes for disorders of sex development (DSD). Our center is currently enrolling patients to evaluate outcomes of modern genitoplasty as part of a National Institutes of Health study (Prime recipient: Dr. Amy Wisniewski, University of Oklahoma Health Sciences Center). This multi-site study comes at a critical point to resolve the debate around the medical treatment approaches for children with DSD and findings from this study will inform clinical practice in the future.

Basic Science

Dr. Poppas and Dr. Diane Felsen have been co-directing the Institute for Pediatric Urology Research lab since 1996. The Institute for Pediatric Urology Research Laboratory is located within the new 5,617 square foot Peter M. Sacerdote Urological Research Laboratory that opened in 2009.

SS-Peptides: Novel Mitochondria-targeted therapeutics

SS-31 is part of a family of small peptides that target the inner mitochondrial membrane. Described in 2004 by Hazel Szeto and colleagues [J Biol Chem 279: 34682, 2004], these peptides target cardiolipin and restore cellular bioenergetics. The SS-peptides have shown remarkable efficacy in attenuating and reversing damage in renal ischemia, in improving bioenergetics and performance in aged skeletal muscle, in reversing visual decline in type I and type II diabetes models and many other disease processes characterized by mitochondrial dysfunction [Szeto HH & Birk AV. Clin Pharm Ther 96:672, 2014]. SS-31 [under the name Elamipretide] is currently in clinical trials, as a "first in class" drug for use in heart failure and in mitochondrial myopathies In our lab we showed that SS-31 attenuated fibrotic and apoptotic damage in the obstructed kidney model [Mizuguchi et al, AJP Renal 295: F1545, 2008]. We are currently investigating its efficacy in a rat torsion model, and in rat models of bladder dysfunction.

Ureteral Obstruction

A major focus of the lab has been the study of the obstructed kidney. In children, the most commonly detected prenatal anomaly is hydronephrosis, the dilation of the renal collecting system. This results from several conditions including UPJ [ureteropelvic junction] obstruction, vesicoureteral reflux, megaureter or posterior urethral valves. In UPJ obstruction, there is a kink or stricture of the collecting system as it begins to leave the kidney to form the ureter. This causes blockage of urine flow and can lead to long-term damage of the kidney. Our laboratory has had a long-standing interest in the molecular mechanisms of damage to the kidney after obstruction, especially the fibrotic response, in which there is a pathologic accumulation of extracellular matrix proteins, which damage the kidney and reduce its function. One of the first events in the obstructed kidney is the build-up of pressure, which results from obstruction of the ureter. We are currently examining the effects of pressure on isolated kidney cells, to determine what signaling pathways are activated by pressure.

Bladder Dysfunction

Bladder dysfunction related to small, fibrotic bladders is a significant problem in children, resulting in high bladder storage pressures and low bladder volume. The high pressures that build up impact upon bladder function by inducing fibrosis and on quality of life because of incontinence; if left untreated, high bladder pressure can lead to renal failure and a lifetime of dialysis, or renal transplantation. MicroRNA's [miRNAs] are small non-coding RNA's that regulate gene expression. We are currently examining the role of miRNAs on bladder smooth muscle cells.

Dr. Poppas details our research on developing a synthetic bladder augmentation device for treatment of pediatric bladder dysfunction:

Wound Healing

The healing of acute cutaneous wounds requires interactions among cytokines, immune cells, parenchymal cells, and components of the extracellular matrix. This process is dynamic and results in scar formation, which restores functional continuity in the affected area. Compromise of the wound-healing process contributes to significant morbidity and even death. Annually, nearly 6 million adults in the United States suffer from some form of acute or chronic wound, and costly treatment modalities remain ineffectual. Children heal better than adults, and we are interested in studying the differences between pediatric and adult wound healing with the eventual goal of improving wound healing.

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