Restricted Research - Award List, Note/Discussion Page
Fiscal Year: 2023
2348 The University of Texas at San Antonio (144236)
Principal Investigator: Flores, Mario
Total Amount of Contract, Award, or Gift (Annual before 2011): $ 328,749
Exceeds $250,000 (Is it flagged?): Yes
Start and End Dates: 3/1/22 - 2/28/24
Restricted Research: YES
Academic Discipline: Engineering and Integrated Design
Department, Center, School, or Institute: Ceid Elec & Comp Engineering
Title of Contract, Award, or Gift: KSHV hijacks FAM50A to alter transcript splicing and induce cellular transformation
Name of Granting or Contracting Agency/Entity:
University of Pittsburgh Medical Center
CFDA Link: HHS
93.396
Program Title:
none
CFDA Linked: Cancer Biology Research
Note:
SAMs 1.1.1; The objective of this research project is to systematically map the dynamics of m6A modifications at a single base resolution and bindings of m6A reader proteins in KSHV epitranscriptome, and determine their functions in different phases of KSHV life cycle, and KSHV-induced tumorigenesis. The Central Hypothesis is that KSHV m6A modifications are dynamically regulated, and these modifications mediate different phases of KSHV life cycle, and hence KSHV-induced tumorigenesis. We will test this hypothesis by mapping m6A marks in KSHV transcriptome at a single base resolution, and determine the roles of m6A writer and eraser proteins in different phases of KSHV life cycle and KSHV-induced tumorigenesis (Aim 1); determining the functions of m6A reader proteins in different phases of KSHV life cycle by gain- and loss-of-function approaches and by examining their bindings to KSHV transcripts (Aim 2); and examining the functions of KSHV m6A marks in the context of viral infection using Crispr-Cas9-guided m6A writer and eraser, and by site-specific mutagenesis (Aim 3). It is our expectations that this project will provide comprehensive mapping and functional delineation of m6A marks, and m6A writer, eraser and reader proteins in different phases of KSHV life cycle, and KSHVinduced tumorigenesis. This work is highly significant as it will, for the first time, systematically reveal the functions of these RNA modifications in KSHV infection, thus providing insights into the mechanism regulating KSHV life cycle and KSHV-induced pathogenesis. This study will also identify potential prognostic markers and therapeutic targets. The proposed work is highly innovative as it will use new technologies to map m6A marks and bindings of m6A reader proteins, as well as directly manipulate m6A marks on key viral transcripts by Crispr-Cas9-guided m6A writer and eraser, KSHV reverse genetics, and innovative tumor models. Furthermore, the generated datasets, information and reagents will be valuable to the scientific community.
Discussion: No discussion notes