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Cathy Lee  Mendelsohn
Cathy Lee Mendelsohn
Associate Professor of Urology, Pathology & Cell Biology (Institute of Human Nutrition) and Genetics & Development


Address: 1130 St. Nicholas Avenue Irving Cancer Research Center Room 311 New York NY 10032
Phone: 212-851-4781
Fax:
E-mail:

clm20@columbia.edu

Education and Training:
Ph.D 1989, Columbia University
Postdoctoral Research Fellow 1989-1994, IGBMC
Postdoctoral Research Fellow 1994-1997, Columbia University
Affiliations:
bullet  Department of Urology
bullet  Department of Pathology
bullet  Institute of Human Nutrition
bullet  Irving Cancer Center
bullet  Integrated Program in Cellular, Molecular & Biophysical Studies
Training Activities:
Research Summary:
(800 words, max)
Understanding urogenital tract formation and identifying the causes of UGT congenital malformations.
Current Research:
The organs lining the upper and lower urinary outflow tract form independently but must connect during development when the ureters are transposed from their primary insertion site in the male genital tract to the bladder. Failure in this process results in a wide range of congenital malformations affecting newborns, some of which can severely damage the kidney leading to end stage renal disease. Our studies are focused at understanding how the kidney, ureter bladder and urethra develop independently and how these organ systems connect during development. Our goal is to use mouse models of normal and abnormal development to identify cellular mechanisms and molecular pathways that are crucial for normal urinary tract formation as a means to identify causes of birth defects in humans.

Epithelial-Mesenchymal Signaling During Kidney Development Mediated by Vitamin A and Ret.

The renal collecting duct system develops via a process of dichotomous branching from a single epithelial bud. Our previous studies demonstrated that retinoic acid is required for branching of the embryonic kidney, and is crucial for maintaining expression of Ret, a receptor tyrosine kinase required for formation of the renal collecting duct system. Retinoic acid is synthesized in stromal mesenchyme surrounding ureteric bud tips and Retinoid receptors are expressed both in stromal mesenchyme and in the ureteric bud, hence it is not clear whether retinoid receptor signaling is required in stroma, inducing expression of secreted signals controlling Ret, or directly in ureteric bud cells. Our current studies are aimed at elucidating transcriptional mechanisms required for Ret regulation by retinoids, and identifying which renal cell types mediate retinoid signaling by introducing dominant negative retinoid receptors into ureteric bud epithelia and stromal mesenchyme to assessing whether blockage of retinoid signaling results in loss of Ret expression and impaired branching morphogenesis.

Epithelial cell remodeling during urinary tract formation:
The urinary outflow tract includes the kidney, ureters, bladder and urethra. The kidney collects toxic substances from the blood in urine, which is propelled through the ureters via peristalsis to the bladder for storage and excretion. The upper and lower urinary tract tissues form independently but must connect in order to generate a patent outflow tract. Ureters are initially joined to the Wolffian ducts, epithelial tubes that form the male genital tract, and but then detach and move from this initial insertion site to the bladder, the final insertion site. Defects in this process (ureter transposition) results in an array of congenital malformations, including obstruction and reflux, both of which can severely damage the kidney.

According to the medical textbooks, ureter transposition depends on remodeling of the terminal portion of Wolffian duct into a structure called the trigone, which becomes part of the bladder floor. Our recent studies indicate that the currently accepted models of ureter transposition are unlikely to be valid, and that separation of the ureter from the Wolffian duct depends on apoptosis of the terminal segment of Wolffian duct and that signals that induce apoptosis are likely to be secreted from the bladder. In addition, we find that the trigone forms from the same tissue as the bladder (urogenital sinus) and is not formed from the Wolffian ducts. We are currently studying this process to identify signals required in epithelial cells for apoptosis, and signals from bladder tissue that may be important for inducing apoptosis in Wolffian duct epithelia, using tissue culture models, and mouse models with abnormal ureter transposition.

Publications:
(6 max)
1. Rosselot, C., Spraggon, L., Chia, I, Batourina, E., Riccio, P., Lu, B., Niederreither, K., Dolle, P., Duester, G., Chambon, P., Costantini, F., Gilbert, T., Molotkov, A. and Mendelsohn, C: (2009) Non-cell autonomous retinoid signaling is crucial for renal development.  Development  (in press)

2. Chi X, Michos O, Shakya R, Riccio P, Enomoto H, Licht JD, Asai N, Takahashi M, Ohgami N, Kato M, Mendelsohn C, Costantini F: (2009) Ret-dependent cell rearrangements in the Wolffian duct epithelium initiate ureteric bud morphogenesis
.  Developmental Cell  2: 199-209. PMCID: PMC2762206

3. Mendelsohn C: (2009) Using mouse models to understand normal and abnormal urogenital tract development.  Organogenesis  1: 306-314. PMCID: PMC2659372

4. Viana, R., Batourina, E., Huang, H., Dressler, G.R., Kobayashi, A., Behringer, R.R., Shapiro, E., Hensle, T., Lambert, S. and Mendelsohn, C: (2007) The development of the bladder trigone, the center of the anti-reflux mechanism.  Development  134: 3763-3769

URL for lab page:
 

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