Background: Small non-coding RNAs including microRNAs and tRNA-related fragments (tRFs) are important
regulators of global gene expression and have been shown to play key roles in normal development. Recent
evidence suggests small RNAs (especially tRFs) can be regulated via modifications, however global analysis
of small RNA modifications in cancers is still lacking due to lack of tools. In this proposal I will test whether
dysregulation of small RNA modifications play a role in cancer biology. I will focus on glioma/glioblastoma
(GBM), vicious cancer types that are barely treatable.
Research: The candidate's preliminary results indicate that tRFs are novel regulators of gene expression and
cell phenotypes in gliomas and their activity could be regulated by small RNA modification status. The
candidate already detected such small RNA modifications in GBM and GSC (glioma stem-like cells) cell lines
and also GBM patients. This proposal aims to understand the biological functions of these newly identified
small RNA modifications and tRFs in gliomas. If completed, this will bring novel insights to the field and be a
perfect niche to launch an independent lab. Three aims are proposed, each based on preliminary data, and
taking into the independent phase. Aim 1 will determine the glioma-relevant small RNA modification factors.
Aim 2 will define the functional roles and targetome of glioma-prognostic tRFs. Aim 3 will elucidate novel RBP-
based mechanisms of small RNA modification regulating tRF targetome and pathways in gliomas. GSC
cultures and mouse xenografts, genomics and bioinformatics will be employed to tackle these questions. The
proposed research plan will reveal a novel gene regulatory mechanism by small RNA modifications and
identify potential therapeutic targets for glioma treatment.
Candidate: The candidate's long-term goal is to utilize her background in biochemistry, small RNA and
molecular biology to understand new gene regulatory mechanism in cancer biology. She already processes a
lot of the skills needed to conduct proposed experiments, however she is in great need to obtain additional
training in glioma biology in order to further test her hypothesis (with co-mentor who is an expert in GBM field).
The K99 mentored phase will allow her to build on her current data, expand on several new areas, and learn
new techniques to launch her own lab. A mentoring committee of 6 is proposed to ensure the candidate get
guidance to help her achieve independence.
Environment: The proposed project will be conducted at University of Virginia, which has an outstanding
environment for the proposed training and research.