Weill Cornell Medicine Urology
Weill Cornell Medicine Urology
Diane Felsen
Headshot: 

Diane Felsen, Ph.D.

Research (pediatric urology)
Headshot: 

Biography

Body: 

Dr. Felsen received her BA degree from Queens College and her PhD in Pharmacology from the Mt. Sinai School of Medicine. She was a post-doctoral fellow in the laboratory of Dr. Philip Needleman in the Dept. of Pharmacology at Washington University in St. Louis, studying renal prostaglandin synthesis in the obstructed kidney. Following completion of the fellowship, she was recruited by then chairman E. Darracott Vaughan, Jr. to join the faculty at Weill Cornell.


Dr. Felsen is currently the co-director, with Dr. Dix P. Poppas, of the Institute for Pediatric Urology Research Laboratory at Weill Cornell. The laboratory has several areas of interest including the following:


Congenital Adrenal Hyperplasia

Congenital Adrenal Hyperplasia [CAH] is an autosomal recessive disease, resulting in inherited enzymatic deficiencies in cortisol synthesis. The most common form of CAH is a deficiency in CYP21A2 (21-hydroxylase ), accounting for over 90% of all cases. CYP21A2 and its nonfunctional pseudogene (CYP21A1P) are located in the HLA region III on the short arm of chromosome 6 (6p21.3). Both genes contain 10 exons each, spaced over 3.1 kb, with their exon and intronic sequences 98% and ∼96% identical, respectively. Most of the mutant alleles in CYP21A2 are generated by recombination between the pseudo and active genes. CAH is found in a more severe Classic form, and a less severe form often appearing later in life, nonclassic CAH. More than 100 unique mutations have been found in CAH. In Classic CAH, there is a general correlation between genotype and phenotype; however, the clinical manifestations of nonclassic disease are quite variable, suggesting that other factors (genetic, epigenetic or environmental) may affect the phenotypic expression. Our current research is focused on using the zebrafish model to study the complex genetics of CAH and the use of CRISPR technology to repair the 21-hydroxylase defect.

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.

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.

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.

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. We are also evaluating the effectiveness of SS-31 peptides in bladder dysfunction.

© 2016 Weill Cornell Medicine All rights reserved.