Fox Chase Researcher Receives Grant for Study of RNA, Telomerase and Implications for Disease

A Fox Chase Cancer Center researcher has been awarded a $2.5 million grant from the National Institute of General Medical Sciences (NIGMS) to investigate RNA structure and stability, work that has implications for cancer, Alzheimer’s, and other degenerative diseases and continues the Fox Chase legacy of basic research.

Lu Chen, PhD, an Assistant Professor in the Nuclear Dynamics and Cancer Research Program and a member of the Cancer Epigenetics Institute, has received an NIGMS Maximizing Investigators’ Research Award. Considered on par with an R01 — the oldest and more common “workhorse” biomedical research grant — the MIRA provides more funds and flexibility, giving investigators the freedom to explore new concepts.

“We’re fortunate in that this was our first try,” Chen said of applying for the grant. “Our 100% hit rate will soon go down but we will capitalize the funding momentum as much as we can.”

Chen and his team will use the grant to explore the use of cutting-edge RNA mapping techniques to probe RNA structure and location inside living cells. “We’re trying to find a way to understand how the RNA structure and location are in turn contributing to RNA’s function inside of a cell,” Chen said.

RNA is an essential component of the enzyme telomerase, which synthesizes the ends of the telomeres found at the tips of chromosomes. Telomerase helps enable 90% of cancer cells to replicate indefinitely. However, when stem cells don’t have enough telomerase due to aging or genetic mutations, they begin to shut down and enter into a terminal state called “replicative senescence.” This contributes to degenerative diseases like dyskeratosis congenita, pulmonary fibrosis, liver cirrhosis, and Alzheimer’s.

Chen’s research is based on work he presented in May at the 13th CSHL-Telomere and Telomerase meeting at the Cold Spring Harbor Laboratory. That described what Chen calls “the telomerase prison break model.” When dismantled, the model “cells,” which are made up of restrictive compartments of RNA and protein molecules, including telomerase, produced additional telomerase. In addition, the “prison break” telomerase elongated human telomeres in cancer cells and in human stem cells harboring mutations linked to degenerative diseases.

Chen said he is gratified to receive the grant at this early point of his career.

“With most of these R-grants from NIH, the investigator usually has to try multiple times,” Chen said. “Junior principal investigators usually get it years later in their tenure or when they start a lab. However, in our case, we got extremely lucky … We submitted the grant in our first year, and then it got granted in the second year… I think that’s in part a testament to the intellectual and supportive environment of Fox Chase.”

That environment includes “a very supportive network,” top-notch facilities, and a collegial atmosphere in which senior faculty members support junior faculty’s grant applications, he said. “All of these positive factors came together in favor of this particular grant. The NIH grant reviewers definitely took notice of the ‘special sauce’ of ‘Fox Chaseness.’”

He noted that the grant also benefitted from the work of talented trainees and the fact that Fox Chase offers “fertile intellectual soil.” Budding scientists “are readily attracted by the name of Fox Chase, and they’re willing to come to the door and get trained at the beginning stage of their career.”