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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)
  • PI, George M. O'Brien Urology Research Center
Cathy Lee Mendelsohn, PhD

Dr. Mendelsohn obtained a BS in Microbiology from the University of Massachusetts at Amherst. She obtained a PhD in Microbiology at Columbia University Medical Center, working in Dr. Vincent Racaniello's lab where she cloned the human Poliovirus receptor. Her postdoctoral studies in Pierre Chambon's lab, at the Université Louis Pasteur, Strasbourg France were focused on Retinoic acid receptors and their role in development, studies which were continued in the lab of Jane Dodd at Columbia University looking at  the role of retinoids in kidney development. 

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

  • Identification of progenitors important for formation and regeneration of the urothelium
  • Stem cell populations that give rise to bladder cancers
  • Genetics of lower urinary tract malformations as part of the Columbia University O'Brien Research Center (http://cumcobriencenter.com/)
  • Generating a molecular and cellular atlas of the mouse and human lower urinary tract (https://beta.gudmap.org/tutorials/urogenital-dev/)
  • Role of Pparg in urothelial development, regeneration and bladder cancer

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

  • Project 1. Identification of progenitors important for Urothelial Development and Regeneration, and cells of origin for bladder cancer. The urothelium is a specialized barrier extending from the renal pelvis to the bladder neck that is critical for preventing exchange of water and toxic substances between the urinary tract and the blood. The urothelium is also a source of cells that generate different types of bladder cancers, including carcinoma in situ, papillary carcinoma, invasive cancers and squamous cell carcinoma. The urothelium is nearly quiescent but can rapidly regenerate in response to injury from toxic substances or urinary tract infection with Uropathogenic E.coli. The urothelium consists of 3 known cell types, Superficial cells, Intermediate cells and Basal cells. Superficial cells are specialized for synthesis and transport of uroplakins, a family of proteins that assemble into a tough crystalline barrier lining the urinary outflow tract. Superficial cells are binucleated and contain a DNA content of 8n. Our recent studies indicate that they are formed by failed cytokinesis, in which cells enter mitosis but failed to complete cytokinesis. Our studies further indicate that both binucleated Intermediate cells and Superficial cells can undergo endoreplication, entering S-phase to increase their DNA content without passing through mitosis.  Intermediate cells are self-renewing Superficial cells during homeostasis and after acute injury, while after chronic injury accompanied by inflammation, the Intermediate cell population is depleted, and basal cells begin producing Intermediate cells, which produce Superficial cell daughters. Our current work on this project is aimed at identification of the genetic changes in basal cells that lead to increased regenerative capacity.

  • Project 2. Characterization transcriptional signaling pathways that regulate urothelial development and regeneration. Our previous studies identified retinoids as critical regulators of urothelial development and regeneration. We find that retinoids, which are secreted by stromal cells, activate Retinoic acid receptors (Rars) expressed in P-cells, a stem cell population that produces both Intermediate and Basal cells.  We find that retinoid signaling is high between E11 and E13, when P-cells generate Intermediate cell daughters, and is down-regulated after E14, when P-cells give rise to basal cells. We showed using a dominant negative allele of Rar (Rosa26R;RaraDN) to block RA-signaling in the developing urothelium, that impaired retinoic acid signaling prevents P-cells from producing Intermediate cells and promotes formation of an abnormal squamous population of basal cells (Krt14+/K5+) cells. Expression of the dominant negative RA-receptor in the adult urothelium impairs urothelial regeneration and results in squamous metaplasia, in which the urothelium is replaced by a keratinized squamous epithelium resembling skin, which is likely to be derived from endogenous basal cells.

  • Project 3: Role of Pparg in urothelial development, homeostasis and in bladder cancer. Expression profiling of RaraDN mutants during development revealed that Pparg, a member of the nuclear receptor superfamily, was down-regulated. Pparg is a critical regulator of lipid metabolism, and Pparg mutations are associated with bladder cancer. Analysis of Pparg mutants during development and in adults reveals a number of phenotypes that are also present in Rar mutants. We find that Pparg mutants fail to produce Intermediate cells during development, and instead produce basal cells (K14+/K5+), and during adulthood, Pparg is required in basal cells, for suppressing squamous differentiation and for maturation and survival of Superficial cells. These observations suggest that Pparg may act downstream of retinoids in the urothelium during development, and in adults. Current projects are focused on generating RNAseq expression data and chip-seq data to identify transcriptional targets of Pparg in the urothelium.

    Work from the TCGA and other groups identifies gain of function and loss of function Pparg mutations in bladder cancer lesions of the luminal and basal subtype, respectively. We have generated GOF and LOF mouse models to examine the effects of these mutations in the adult urothelium. These animals will serve as models for investigating the molecular changes and cellular behavior during tumor formation which will be validated in bladder cancer lesions from human patients.

  • Project 4. Generating an atlas of cell types in the mouse and human urothelium. As part of the Genitourinary Tract Development Molecular Anatomy Consortium (http://www.gudmap.com/) we are generating expression profiles of urothelial cell types from the mouse and human as well as adjacent stroma during development, and in adults. Data is being collected using a combination of bulk RNAseq and scRNAseq, which will be validated and uploaded onto the GUDMAP and GEO websites, available to the public. The goal of these studies is producing a "map" of the distribution of stromal-epithelial signaling pathways that control development and patterning in the lower urinary tract.

  • Project 5. The genetic origins and complications of urinary tract abnormalities. Columbia University George M. O’brien Urology Research Center  (http://cumcobriencenter.com).  Co-PIs: Cathy Mendelsohn, PhD, Jonathan Barasch, MD PHD, Ali Gharavi, MD. 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 is a NIH funded project that 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 minorities.

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

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