The research component of this Center will employ novel intact lower urinary tract (LUT) explants, video microscopy, and optical mapping techniques to provide the urological community, and investigators outside the realm of this discipline, with the tools for real---time systems level analysis of UT smooth muscle activity, which is currently lacking. Video microscopy and optical mapping analyses of intact ureter and bladder explants will be used to document the contractile and electrical excitation patterns within intact tissues and within specified regions of these urinary tract segments in wild type and mutant murine models of hydronephrosis and overactive bladder syndrome. Data will be processed and analysed using custom written software that incorporates advanced mathematical algorithms that enable the differentiation of membrane voltage signals and experimental noise, as well as the representation of membrane depolarization data as spatial temporal excitation maps and action potential contours. High---resolution movies and time lapse images of representative real---time video microscopy will be performed to correlate electrical and contractile activity. Thus, our core will provide a comprehensive analysis of large scale LUT motility patterns and pave the way for the generation of novel diagnostics and drugs to alleviate UT motility defects such as in---born functional UT obstructions and overactive active bladder syndrome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory Grants (P20)
Project #
5P20DK103072-02
Application #
8879133
Study Section
Special Emphasis Panel (ZDK1)
Project Start
Project End
2017-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
2
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Herzlinger, Doris; Hurtado, Romulo (2014) Patterning the renal vascular bed. Semin Cell Dev Biol 36:50-6
Hurtado, Romulo; Bub, Gil; Herzlinger, Doris (2014) A molecular signature of tissues with pacemaker activity in the heart and upper urinary tract involves coexpressed hyperpolarization-activated cation and T-type Ca2+ channels. FASEB J 28:730-9
Herzlinger, Doris (2011) Upper urinary tract pacemaker cells join the GLI club. J Clin Invest 121:836-8
Hurtado, Romulo; Bub, Gil; Herzlinger, Doris (2010) The pelvis-kidney junction contains HCN3, a hyperpolarization-activated cation channel that triggers ureter peristalsis. Kidney Int 77:500-8