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Principal Investigator: Dr. Norine Tallini
Mentor: Dr. Michael Kotlikoff
Contact Information: E-mail: nyt2@cornell.edu - Phone: 607-253-3336
Sponsor: NIH
Grant Number: 1F32HL076999-01A1
Title: Models of Airway Smooth Muscle Hyperplasia
Annual Direct Cost: $48,296
Project Period: 05/01/05-04/30/08
Asthma is characterized by airway narrowing due to inflammation and constriction. Changes in chronic asthmatic airway smooth muscle (ASM) cells include an increase in their mass. These changes may explain the increase in the capability and velocity of ASM to shorten. While smooth muscle proliferative stimuli and phenotype switching has been well established in vitro, neither the specific signals leading to proliferation, nor the phenotypic consequences, have been established in vivo. It has been proposed that platelet derived growth factor (PDGF) may be responsible for the hyperplasia observed in ASM. In this proposal the consequences of constitutively active and inducible time-dependent overexpression of PDGF on smooth muscle proliferation, Ca2+ signaling and transcriptional activity will be examined. A novel mouse that expresses a Ca2+-sensitive fluorescent protein in smooth muscle will be used to examine Ca2+ signaling in control and PDGF overexpressing mice. In addition, a mouse in which the smooth muscle cells contain a green fluorescent protein will be used to separate ASM from other cell types in the lung to examine cell size and determine transcriptional activity of the smooth muscle promoter.
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