Title |
(PQ2) HIV INFECTION, APOBEC UPREGULATION, AND CANCER MUTAGENESIS
|
Institution |
UNIVERSITY OF MINNESOTA, MINNEAPOLIS, MN
|
Principal Investigator |
HARRIS, REUBEN
|
NCI Program Director |
Read_Connole
|
Cancer Activity |
Cancer Etiology
|
Division |
DCB
|
Funded Amount |
$182,192
|
Project Dates |
05/10/2016 - 04/30/2018
|
Fiscal Year |
2017
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Cancer (100.0%)
|
N/A
|
Research Type |
Cancer Initiation: Alterations in Chromosomes
|
Abstract |
"? DESCRIPTION (provided by applicant): The incidence of several types of cancer is higher in HIV-1 infected patients in comparison to the general population. Little is known about the mechanistic basis for these observations. This R21 proposal addresses RFA-CA-15-013 and, specifically, provocative question 2: ""Other than immune dysfunction (including inflammation), what are the HIV-mediated mechanisms that underlie differential cancer risk in individuals with HIV infection?"" We will use molecular virology and molecular biology approaches, together with bioinformatics, to investigate a mechanistic link between viral infection of CD4-positive T lymphocytes and a signaling mechanism that causes the trans-upregulation of antiviral APOBEC3 enzymes in bystander cells, leading to increased levels of genomic mutation that in turn result in a higher likelihood of cancer. The demonstration of such a mechanism would be a significant advance because it is novel and suggests multiple points for therapeutic intervention. " |