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Cathy Lee Mendelsohn, PhD

  • Professor of Urological Sciences (in Urology) and Pathology & Cell Biology and Genetics & Development (in the Institute of Human Nutrition)
Cathy Lee Mendelsohn, PhD

My background is in developmental biology, examining therole of retinoids in different aspects of organogenesis. Several years ago my lab used mouse models to establish the sequence of events that occur during ureter maturation, a process where primitive ureters make direct connections with bladder, which when defective, is a common cause of urinary tract dysfunction. Mutants with abnormal Retinoic acid signaling develop massive bilateral hydronephrosis. Our studies suggest that these abnormalities are linked to defective apoptosis during ureter maturation, which normally depends on Casp-9. Our findings further suggest that Casp9 may be a direct transcriptional target of retinoids. We are currently part of a George O’Brien Urological Center, in collaboration with Jon Barasch and Ali Gharavi from the Dept. of Medicine. Our collective projects are focused on using mouse models to identify mutations that in humans, are linked to urinary tract abnormalities, including VUR and posterior urethral valves, a condition inherited by males that severely affects renal function about which little is understood. Most recently, my lab has focused on identification and characterization of progenitors that are important for development and regeneration of the urothelium, a water-proof barrier that lines the urinary outflow tract. The urothelium is also a source of epithelial cells that give rise to urothelial carcinoma. We find that retinoids are important for producing and regenerating superficial cells, a luminal population that establishes and maintains the urothelial barrier. We find that Pparg, a transcription factor best known for it’s role in fat metabolism, is a likely downstream target of retinoids in the urothelium where Pparg plays an important role in development and regeneration, and acts as a modulator innate immunity in response to urinary tract infections. Pparg expression is down-regulated in the basal subtype of urothelial carcinoma, a lesion that displays squamous properties. Our studies with Pparg mutant mice suggest that Pparg may be normally be critical for preventing squamous differentiation and urothelial carcinoma.

Email: clm20@cumc.columbia.edu 

My background is in developmental biology, examining the role of retinoids in different aspects of organogenesis. Several years ago my lab used mouse models to establish the sequence of events that occur during ureter maturation, a process where primitive ureters make direct connections with bladder, which when defective, is a common cause of urinary tract dysfunction. Mutants with abnormal Retinoic acid signaling develop massive bilateral hydronephrosis. Our studies suggest that these abnormalities are linked to defective apoptosis during ureter maturation, which normally depends on Casp-9. Our findings further suggest that Casp9 may be a direct transcriptional target of retinoids.  We are currently part of a George O’Brien Urological Center, in collaboration with Jon Barasch and Ali Gharavi from the Dept. of Medicine. Our collective projects are focused on using mouse models to identify mutations that in humans, are linked to urinary tract abnormalities, including VUR and posterior urethral valves, a condition inherited by males that severely affects renal function about which little is understood. Most recently, my lab has focused on identification and characterization of progenitors that are important for development and regeneration of the urothelium, a water-proof barrier that lines the urinary outflow tract. The urothelium is also a source of epithelial cells that give rise to urothelial carcinoma. We find that retinoids are important for producing and regenerating superficial cells, a luminal population that establishes and maintains the urothelial barrier. We find that Pparg, a transcription factor best known for it’s role in fat metabolism, is a likely downstream target of retinoids in the urothelium where Pparg plays an important role in development and regeneration, and acts as a modulator innate immunity in response to urinary tract infections. Pparg expression is down-regulated in the basal subtype of urothelial carcinoma, a lesion that displays squamous properties. Our studies with Pparg mutant mice suggest that Pparg may be normally be critical for preventing squamous differentiation and urothelial carcinoma. 

Progenitor populations and signaling pathways important for their regulation.

Languages Spoken

  • French

Education & Training

  • PhD, 1989 Microbiology, Columbia University Graduate School of Arts and Sciences, NY

Lab Locations

  • Irving Cancer Research Center

    1130 Street Nicholas Avenue
    New York, NY 10032
    Phone:
    (212) 851-4781
    Lab Phone:
    (212) 851-4783
    Email:
    clm20@cumc.columbia.edu

Contact Info

Research Interests

  • Molecular pathways controlling development of urogenital tract

Grants

U54 DK104309, (MENDELSOHN)  09/24/2014-07/31/2019   
“The Genetic Origins and Complications of Urinary Tract Abnormalities” The George M. O'Brien Center Urology Center. The overall focus of this award is to identify mutations in humans that cause urological birth defects and to provide outreach to the community with the goal of attracting new investigators to the field. Role: Principal Investigator 

R01 DK095044-03 (MENDELSOHN)  07/01/2013-06/30/2022   
“Retinoic acid signaling controls urothelial development and regeneration”. 
This project is focused on elucidating the role of retinoid-dependent transcription in urothelial progenitor cells. Role: Principal Investigator 

TJ Martell foundation    
"Lineage studies of bladder cancer"  
This project is focused on analyzing the cancer forming potential of urothelial cells using mouse models of bladder carcinogenesis. 
Role: Co-Investigator 

U01 DK094530-05 (MENDELSOHN)  09/30/2011-08/31/2021 
“Generating molecular markers that selectively label urothelial sub-populations.” 
This project is focused on producing an anatomical atlas of the mouse and human urinary tract. Role: Principal Investigator 

NIH Grants

  • RETINOIC ACID SIGNALING CONTROLS UROTHELIAL DEVELOPMENT AND REGENERATION. (Federal Gov)

    Jul 1 2017 - Jun 30 2022

    GENERATING AN ATLAS OF THE DEVELOPING HUMAN URINARY OUTFLOW TRACT. (Federal Gov)

    Sep 15 2016 - May 31 2021

    THE GENETIC ORIGINS AND COMPLICATIONS OF URINARY TRACT ABNORMALITIES (Federal Gov)

    Sep 24 2014 - Jul 31 2019

    GENERATING MOLECULAR MARKERS THAT SELECTIVELY LABEL UROTHELIAL SUB-POPULATIONS. (Federal Gov)

    Sep 1 2011 - Aug 31 2017

    THE T.J. MARTELL FOUNDATION FOR LEUKEMIA, CANCER AND AIDS RESEARCH (Private)

    Jan 1 2015 - Dec 31 2015

    SUPPLEMENT TO URINARY BIOMARKERS OF LOWER URINARY TRACT SYMPTONS (LUTS) IN MEN (Federal Gov)

    Jul 1 2014 - Aug 31 2015

    A PROSTATE CANCER PROGRAM (Private)

    Jan 1 1999 - Dec 31 2014

    REGENERTION, REPAIR AND REMODELING OF THE LOWER URINARY TRACT (Federal Gov)

    Sep 9 2013 - Jul 31 2014

    MOLECULAR EVENTS IN URINARY TRACT FORMATION (Federal Gov)

    Apr 30 2002 - Aug 31 2013

    VITAMIN A DEPENDENT EVENTS IN URINARY TRACT FORMATION (Federal Gov)

    Sep 15 2009 - Aug 31 2011

    MURINE ATLAS OF A GENITOURINARY SMOOTH MUSCLE (Federal Gov)

    Apr 1 2008 - Mar 31 2011

    MURINE ATLAS OF A GENITOURINARY SMOOTH MUSCLE DEVELOPMENT (Federal Gov)

    Apr 1 2008 - Mar 31 2011

    APOPTOSIS REQUIRED FOR URETER TRANSPORTATION (Private)

    Jan 1 2006 - Dec 31 2010

Lab Projects

  • Identification of progenitors important for urothelial development and regeneration, and cells of origin for bladder cancer

    1. Using mouse models in fate mapping studies to identify progenitors that give rise to the urothelium during development and regeneration
    2. Defining progenitors that give rise to different subtypes of bladder cancer and identification of molecular changes that drive tumor formation.

  • The genetic origins and complications of urinary tract abnormaliteis.

    Co-PIs: Cathy Mendelsohn, PhD, Jonathan Barasch, MD PHD, Ali Gharavi, MD

    Columbia University George M. O’brien Urology Center

    http://cumcobriencenter.com

    Urinary Tract Obstruction is a collection of abnormalities including Posterior urethral valves, Vesicoureteral reflux and Hydronephrosis that are common birth defects in humans accounting for 20% chronic kidney failure in children. The Columbia University O’Brien Urology Center brings together research programs in Human Genetics and Mouse models to address the causes of congenital urinary tract malformations. Our Center consists of 3 research projects and an administrative core. The scientific aims of our research projects are highly interconnected, focused on identifying the genetic and embryological causes of obstruction and the related events that lead to renal disease. The Administrative Core of the center is focused on promoting vigorous exchange of ideas, data sharing between projects and with other researchers in the field of benign urology. We will accomplish these goals by providing research opportunities for students and fellows, providing research opportunities to under-represented

Lab Members

  • Tiffany Tate, Graduate Student
  • Gregory Weissner, Graduate Student
  • Chang Liu, Graduate Student
  • Jia Wang, Post-doc
  • Ekatherina Batourina, Lab Manager
  • Christopher George, Senior Technician
  • Carl Constant, Masters Student
  • Andrew Romere, Masters Student
  • Alejandra Perez, Medical Student, 4th year
  • Alex Small, Urology Fellow

Publications

An illustrated anatomical ontology of the developing mouse lower urogenital tract.

PubMed Id: 25968320. Authors: Georgas KM Armstrong J Keast JR Larkins CE McHugh KM Southard-Smith EM Cohn MJ Batourina E Dan H Schneider K Buehler DP Wiese CB Brennan J Davies JA Harding SD Baldock RA Little MH Vezina CM Mendelsohn C

Tumorigenicity of RTK/RAS in urothelium.

PubMed Id: 26501074. Authors: Wu XR Mendelsohn C DeGraff DJ

Bladder cancers arise from distinct urothelial sub-populations.

PubMed Id: 25218638. Authors: Van Batavia J Yamany T Molotkov A Dan H Mansukhani M Batourina E Schneider K Oyon D Dunlop M Wu XR Cordon-Cardo C Mendelsohn C

Formation and regeneration of the urothelium.

PubMed Id: 24752063. Authors: Yamany T Van Batavia J Mendelsohn C

Retinoid signaling in progenitors controls specification and regeneration of the urothelium.

PubMed Id: 23993789. Authors: Gandhi D Molotkov A Batourina E Schneider K Dan H Reiley M Laufer E Metzger D Liang F Liao Y Sun TT Aronow B Rosen R Mauney J Adam R Rosselot C Van Batavia J McMahon A McMahon J Guo JJ Mendelsohn C

For a complete list of publications, please visit PubMed.gov