# Dissecting the cis-regulatory roles of transposable elements in human cancers

> **NIH NIH K99** · LUDWIG INSTITUTE  FOR CANCER RES  LTD · 2020 · $113,716

## Abstract

Project Summary/Abstract
 Nearly one half of the human genome consists of transposable elements (TEs), a.k.a. “jumping genes”;
however, we know surprisingly very little about them. The rise of genomic technologies has begun to shed light
on the multi-faceted functions of TEs, but interrogations of their impact on human diseases are still lacking.
The majority of TEs are suppressed in somatic tissues, but some TE families are consistently re-activated in
cancer. It has been revealed that TEs contribute to tumorigenesis both through active transposition and by
providing alternative promoters to drive oncogene expression. However, these mechanisms may represent the
tip of an iceberg. Recent works from Dr. Zhang and others show that TEs can alter higher-order chromatin
architecture (insulator role) and enhance expression of nearby genes (enhancer role). These findings suggest
the intriguing possibility that re-activation of TEs in cancer may similarly remodel higher-order chromatin
structure and cause oncogene and tumor suppressor mis-regulation, thus contributing to tumorigenesis. This
proposal aims to comprehensively characterize the landscape of re-activated TEs in cancer by leveraging
public consortia data, including the cancer genome atlas (TCGA) and cancer cell line encyclopedia (CCLE). Dr.
Zhang will employ genomic assays and reporter assays to determine the enhancer and insulator properties of
TEs in cancer cell lines (Aim 1). Subsequently, Dr. Zhang will computationally predict and experimentally
validate functional impact of TEs as cis-regulatory elements on the nearby oncogenes and tumor suppressor
genes and cancer cell growth (Aim 2). Finally, Dr. Zhang will investigate the mechanisms causing TE over-
expression in cancer cells (Aim 3). Overall, the results from this proposal will reveal new regulatory roles of
TEs in human diseases, and expand our understanding of the mechanisms leading to gene deregulation and
oncogenesis.
 Dr. Zhang's career goal is to lead an independent research group devoted to understanding the
epigenetic dysregulation in human aging and cancer. During the K99 phase, he will continue to receive
computational and experimental training from his postdoctoral mentor Dr. Ren and his advisory committee at
Ludwig Institute and UC San Diego. The rigorous mentored support and results obtained in the K99 phase will
facilitate Dr. Zhang's transition to independence as an investigator in the R00 phase, and lay the foundation for
his future career.

## Key facts

- **NIH application ID:** 10038773
- **Project number:** 1K99CA252020-01
- **Recipient organization:** LUDWIG INSTITUTE  FOR CANCER RES  LTD
- **Principal Investigator:** Yanxiao Zhang
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $113,716
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10038773

## Citation

> US National Institutes of Health, RePORTER application 10038773, Dissecting the cis-regulatory roles of transposable elements in human cancers (1K99CA252020-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10038773. Licensed CC0.

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