Cathy Lee Mendelsohn, PhD

  • Professor of Urological Sciences (in Urology) and Pathology & Cell Biology and Genetics & Development (in the Institute of Human Nutrition)
Profile Headshot

Overview

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 Universite´ 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 urinary tract development.

Academic Appointments

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

Administrative Titles

  • PI, George M. O'Brien Urology Research Center

Languages

  • French

Credentials & Experience

Education & Training

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

Research

Our research focuses on understanding normal and abnormal biology of the urothelium, a water-tight epithelial barrier lining the urinary outflow tract that protects against infection. The urothelium is nearly quiescent, but can rapidly undergo regeneration in response to injury from urinary tract infection or exposure to chemicals. Chronic injury or inflammation however, induces a shift from a urothelial differentiation program to a basal/squamous differentiation program generating an epithelium similar to skin. Our studies have used mouse models to identify major transcriptional and epigenetic regulators of urothelial differentiation both in the healthy urothelium and in bladder cancer, including nuclear receptors (Pparg, retinoids) and chromatin remodeling genes.

Bladder cancers can be divided into distinct classes; Basal/Squamous tumors tend to be invasive, and are immune infiltrated, while luminal/papillary tumors tend to be less invasive, are exophytic, and have low levels of immune infiltration. Pparg, a transcription factor belonging to the nuclear receptor superfamily promotes urothelial/luminal differentiation and suppresses basal/squamous differentiation. At present, most patients with high-grade Basal/squamous tumors undergo cystectomy, while lower grade papillary tumors can be resected by TURBT, but often regrow, and can become invasive. Deficiency in retinoids has long been known to induce squamous differentiation in a number of epithelial including the urothelium. We find that Pparg regulates urothelial differentiation at least in part, by up-regulating retinoid signaling and Kdm6a, a chromatin modifier required for retinoid signaling.

Most recently, our studies have investigated the efficacy of a 2-drug treatment consisting of rosiglitazone, a synthetic Pparg agonist, and trametinib, a MEK/ERK inhibitor. Using a mouse model of basal/squamous muscle invasive bladder cancer, we show that either drug alone can restrict tumor growth, while the 2-drug combination induces tumor cell death within 7 days of treatment. Furthermore, the epithelium of rosiglitazone/trametinib treated mice undergoes a switch from basal/squamous differentiation which promotes tumor formation to urothelial differentiation; restoring endogenous cell types and functions, which are important for bladder stretch and physiology.  An important goal, is translating these preclinical findings into a clinical study which is currently underway.

Grants

  • U54 DK104309
    NIH National Institute of Diabetes and Digestive and Kidney Diseases 
    9/24/2014-7/31/2026
    MENDELSOHN, CATHY LEE (PI) 
    "Investigating the Genetic, Cellular, and Metabolic Events Important for Urothelial Homeostasis and Response to Injury"
  • JPB Foundation
    2021/07/2021-2025-06/30
    MENDELSOHN, CATHY LEE (PI) 
    “Investigating the link between diabetes, urothelial differentiation and bladder cancer”
  • 2022/1/10-present
    Flare Therapeutics
    MENDELSOHN, CATHY LEE (PI)
    "Testing the efficacy of Pparg inverse agonists in bladder cancer models."

Selected Publications

  1. Biswas AK, Han S, Tai Y, Ma W, Coker C, Quinn SA, Shakri AR, Zhong TJ, Scholze H, Lagos GG, Mela A, Manova-Todorova K, de Stanchina E, Ferrando AA, Mendelsohn C, Canoll P, Yu HA, Paik PK, Saqi A, Shu CA, Kris MG, Massague J, Acharyya S. Targeting S100A9-ALDH1A1-Retinoic Acid Signaling to Suppress Brain Relapse in EGFR-Mutant Lung Cancer. Cancer Discov. 2022 Apr 1;12(4):1002-1021. doi: 10.1158/2159-8290.CD-21-0910. PubMed PMID: 35078784; PubMed Central PMCID: PMC8983473.
  2. Tate T, Xiang T, Wobker SE, Zhou M, Chen X, Kim H, Batourina E, Lin CS, Kim WY, Lu C, Mckiernan JM, Mendelsohn CL. Pparg signaling controls bladder cancer subtype and immune exclusion. Nat Commun. 2021 Oct 25;12(1):6160. doi: 10.1038/s41467-021-26421-6. PubMed PMID: 34697317; PubMed Central PMCID: PMC8545976.
  3. Liu C, Tate T, Batourina E, Truschel ST, Potter S, Adam M, Xiang T, Picard M, Reiley M, Schneider K, Tamargo M, Lu C, Chen X, He J, Kim H, Mendelsohn CL. Pparg promotes differentiation and regulates mitochondrial gene expression in bladder epithelial cells. Nat Commun. 2019 Oct 9;10(1):4589. doi: 10.1038/s41467-019-12332-0. PubMed PMID: 31597917; PubMed Central PMCID: PMC6785552.
  4. Wang J, Batourina E, Schneider K, Souza S, Swayne T, Liu C, George CD, Tate T, Dan H, Wiessner G, Zhuravlev Y, Canman JC, Mysorekar IU, Mendelsohn CL. Polyploid Superficial Cells that Maintain the Urothelial Barrier Are Produced via Incomplete Cytokinesis and Endoreplication. Cell Rep. 2018 Oct 9;25(2):464-477.e4. doi: 10.1016/j.celrep.2018.09.042. PubMed PMID: 30304685; PubMed Central PMCID: PMC6351079.