Grant: CIHR Fellowship
Queen's University (Kingston, Ontario)
$135,000.00
Determining the role of E2A-PBX1, CBP/p300 and EBF1 in the onset of acute lymphoblastic leukemia.
EF 2013-14
Résumé
The transcription factor E2A is essential for the regulation of B-cell development. In approximately 25% of pre-B acute lymphoblastic leukemia (ALL) cases, a genetic mutation results in expression of the oncogene E2A-PBX1. E2A-PBX1 is thought to contribute to ALL through irregular signaling of blood cell development, although the exact mechanism is unclear. Preliminary studies suggest that E2A-PBX1 may induce ALL by interacting with two other transcriptional proteins named CREB Binding Protein (CBP/p300) and early B-cell factor 1 (EBF1). My work will focus on determining how E2A-PBX1, CBP/p300 and EBF1 interact to form a ternary complex, where I will determine the molecular structures of portions of E2A-PBX1 and EBF1 bound to CBP/p300. Using this knowledge and microarray technology, will design peptides to disrupt these interactions which will be tested in vitro and in leukemia cell lines. This transdisciplinary project will further develop our understanding of ALL and provide new treatments for the disease.
Programme
CIHR Fellowship
Bénéficiaire
Emplacement
Ontario, Canada
Type
Grant
Source
CIHR Funding Decisions Database
Tel que publié
Id
300773
Name
Langelaan David N
Region
Ontario
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Cancer Research
Theme2
Biomedical
Prcname2
Fellowships - Post-PhD
Projecttitle
Determining the role of E2A-PBX1, CBP/p300 and EBF1 in the onset of acute lymphoblastic leukemia.
Programtype2
Fellowship Programs
Orgnameinp2
Queen's University (Kingston, Ontario)
Cihramount2
$135,000
Cihrequipment2
$0
Programname2
CIHR Fellowship
Keyworddelim
Acute Lymphoblasic Leukemia; Cell Culture; Nucear Magnetic Resonance Spectroscopy; Peptide Inhibitor; Peptide Microarray; Protein-Protein Interaction
Abstract
The transcription factor E2A is essential for the regulation of B-cell development. In approximately 25% of pre-B acute lymphoblastic leukemia (ALL) cases, a genetic mutation results in expression of the oncogene E2A-PBX1. E2A-PBX1 is thought to contribute to ALL through irregular signaling of blood cell development, although the exact mechanism is unclear. Preliminary studies suggest that E2A-PBX1 may induce ALL by interacting with two other transcriptional proteins named CREB Binding Protein (CBP/p300) and early B-cell factor 1 (EBF1). My work will focus on determining how E2A-PBX1, CBP/p300 and EBF1 interact to form a ternary complex, where I will determine the molecular structures of portions of E2A-PBX1 and EBF1 bound to CBP/p300. Using this knowledge and microarray technology, will design peptides to disrupt these interactions which will be tested in vitro and in leukemia cell lines. This transdisciplinary project will further develop our understanding of ALL and provide new treatments for the disease.
Competitiondate
201311
Approvedterm2
3 yrs 0 mth
Pinamesdelim
Langelaan, David N
Approvedterm
3 ans 0 mois
Cihrcontribution2
~ $135,000~ $0~
