Wistar senior staff scientist Zhong Deng, Ph.D., will be honored tonight as one of the recipients of a grant from the American Heart Association. Dr. Deng, a scientist in the lab of Paul M. Lieberman, Ph.D., will receive $308,000 over four years to support his research.
Dr. Deng seeks to prevent heart disease by slowing the rate by which our cells are affected by aging. He and his colleagues hope to do this by tinkering with the molecular hourglass that determines the lifetime of cells: the telomere.
Telomeres are structures that protect the ends of the strands of DNA that make up our genomes. These structures are often compared to the plastic aglets at the end of shoelaces that prevent the laces from unraveling. Telomeres consist of numerous short repeated segments of DNA, and as we age telomeres gradually erode, losing small pieces each time our DNA is duplicated. As such, telomere loss is related to a number of age-associated diseases, such as cancer or cardiovascular disease.
A better understanding of how telomeres deteriorate will provide opportunities for creating new drugs to slow or prevent such deterioration. That is, knowing the enzymes and molecular pathways involved in telomere erosion will allow researchers to design therapies to prevent or slow the damage this erosion causes in heart disease, for example.
In particular, Dr. Deng and his colleagues are interested in understanding how telomeres are protected by an RNA molecule called TERRA (short for telomeric repeat-containing RNA). In classical biology, RNA serves as an intermediate, a so-called “transcript” or copy of the code written in DNA that is then translated into a protein by machinery within the cell. Recently, a great body of evidence suggests that RNA can act as more than an intermediate and actually create its own effects within the cell, such as regulating how the cell reads DNA. TERRA is a form of this non-coding RNA, transcribed from the DNA of the telomere itself.
The Wistar researchers are proposing to use human heart cells to determine how changes in the amount of TERRA affect telomere protection and cellular aging. Dr. Deng hypothesizes that stress associated with cardiovascular aging and disease-risk result in a reduction of TERRA levels and deterioration of telomeres, which in turn, leads to telomere stress and cellular aging. Dr. Deng has already begun to identify the genetic and cellular factors that control TERRA levels in response to cellular stress using genetic and biochemical approaches.
Dr. Deng will be honored tonight at a reception held at the Philadelphia Downtown Marriott, along with researchers from eight other Philadelphia universities and hospitals. The group was collectively awarded $15 million in grants from the heart association for cardiovascular and stroke research and education.