Grant: Operating Grant
Queen's University (Kingston, Ontario)
$640,550.00
E2A proteins in acute lymphoblastic leukemia: Structural and functional analysis and inhibition of oncogenic protein-protein interactions
FY 2009-10
Summary
Acute lymphoblastic leukemia (ALL) is the most common cancer in children. ALL often arises due to defects in the normal development of blood cells, which then grow in an uncontrolled manner. A high percentage of cases of pediatric ALL is caused when the E2A protein, which is normally present in developing B-cells, is fused to another protein PBX1. This linkage disrupts the normal control mechanism in B-cell development. To better understand how E2A contributes to ALL we have recently identified a specific protein that E2A interact with, and that this interaction is key to the onset of ALL. In this new application, we will determine how specific regions of E2A interact with their target protein, what changes in E2A structure affect these interactions, and identify/design small molecule inhibitors that can be used as molecular probes to better characterize the role of E2A-PBX1 in leukemia. Our novel approach could lead to new therapies for treating children afflicted with ALL.
Department
Program
Operating Grant
Location
Ontario, Canada
Type
Grant
Source
CIHR Funding Decisions Database
As published
Id
201151
Name
Smith Steven P
Region
Ontario
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Genetics
Theme2
Biomedical
Prcname2
Biochemistry & Molecular Biology - A
Projecttitle
E2A proteins in acute lymphoblastic leukemia: Structural and functional analysis and inhibition of oncogenic protein-protein interactions
Programtype2
Operating Grants
Orgnameinp2
Queen's University (Kingston, Ontario)
Cihramount2
$640,550
Cihrequipment2
$0
Programname2
Operating Grant
Keyworddelim
B-Cell Development; Biophysical Approaches; Cancer; Nmr; Protein-Protein Interactions; Transcription Factor; X-Ray Crystallography
Abstract
Acute lymphoblastic leukemia (ALL) is the most common cancer in children. ALL often arises due to defects in the normal development of blood cells, which then grow in an uncontrolled manner. A high percentage of cases of pediatric ALL is caused when the E2A protein, which is normally present in developing B-cells, is fused to another protein PBX1. This linkage disrupts the normal control mechanism in B-cell development. To better understand how E2A contributes to ALL we have recently identified a specific protein that E2A interact with, and that this interaction is key to the onset of ALL. In this new application, we will determine how specific regions of E2A interact with their target protein, what changes in E2A structure affect these interactions, and identify/design small molecule inhibitors that can be used as molecular probes to better characterize the role of E2A-PBX1 in leukemia. Our novel approach could lead to new therapies for treating children afflicted with ALL.
Competitiondate
201003
Approvedterm2
5 yrs 0 mth
Pinamesdelim
Smith, Steven P
Approvedterm
5 ans 0 mois
Cihrcontribution2
~ $640,550~ $0~
