Secretory proteins are often robust markers of changes in disease-relevant cellular states including ER stress and metastasis. The absence of technologies for detecting specific luminal secretory proteins in live cells represents a major gap in cell imaging tools. Our goal is to develop and deliver highly sensitive reporters that can detec differences in the expression of diagnostic secretory proteins within a population of live cells. T do this, we will combine three existing technologies to create a new class of imaging tools, STABs (Secretory Targeting Aptamer Beacons). More specifically, by combining modified bacterial toxins with nuclease stabilized aptamer beacons specific for secreted proteins such as VEGF or the UPR-induced endoplasmic reticulum proteins Ero1 and ERdj4, we aim to generate reagents which, when added directly to cells or tissues, will enter the secretory pathway and report the presence of these proteins. Theoretically, up to four distinct fluorescent dyes can be paired with unique aptamers to report on the expression of four different secretory proteins. We envision the probe technology will have utility for basic research and rapid clinical analysis of tissue samples.

Public Health Relevance

Secretory proteins are often robust markers of changes in disease-relevant cellular states including ER stress and metastasis. The proposed work seeks to develop new tools to directly detect the presence of or changes in the levels of proteins within the secretory pathway of na?ve, unperturbed live cells. We envision the probe technology will have utility for basic research and rapid clinical analysis of tissue samples.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA174404-02
Application #
8550032
Study Section
Special Emphasis Panel (ZRG1-CB-D (51))
Program Officer
Knowlton, John R
Project Start
2012-09-24
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$202,488
Indirect Cost
$81,238
Name
Albert Einstein College of Medicine
Department
Biochemistry
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461