UMD Undergraduate Research Journal

The Science of Aging: searching for a solution to Progeria

by Nicholas Hung

HGPS is caused by a single genetic mutation that results in the production of a faulty protein that makes up the structural scaffolding of the cell nucleus. This scaffolding, called the nuclear lamina, has many critical functions besides maintaining the shape of the nucleus, such as controlling gene expression. Here a nucleus from an HGPS patient is shown (left) with an outline demonstrating the abnormal nuclear shape caused by the mutant protein as opposed to the normal shape (right).

Imagine a young child, who, like many other children is new to the world with lots of time to learn and grow. Only, this particular child is lacking something so vital that they are unable to experience life and grow like other children. He is balding so much that superficial veins surrounding his head are visible; his arms and skin are so thin because very little, if any, fat is stored to insulate them; and his skin is wrinkled so that it looks as if he is many times his actual age. This is no ordinary disease, yet it is caused by a single genetic mutation. This is Hutchinson-Gilford progeria syndrome (HGPS), a rare and fascinating disease. Research on HGPS is currently beingconducted on campus by Cell and Developmental Biology Assistant Professor Kan Cao.

Prior to coming to the University of Maryland last September, Cao worked as a post doctoral fellow at the NIH in Bethesda, MD. There, she was introduced to HGPS and discovered that certain cellular mechanisms, such as telomere dysfunction, act together with other mechanisms like progerin production, a product upregulated in HGPS cells, to cause the arrest of further development within a cell. "It's an interesting system because we only have one mutation, which causes multi-tissue defects," Cao said. She and her colleagues at the NIH also discovered that a natural antibiotic, called rapamycin, reversed cellular senescence in HGPS cells through clearance of accumulated progerin, thus enhancing cell development and proliferation.

Nuclei of HGPS fibroblast cells stained with several fluorescent dyes. The green dye indicates the nuclear lamina, while the blue dye indicates DNA. A potential treatment for HGPS was applied to these cells for several weeks, clearly improving the abnormal shape of the nucleus.

Cao and her team, who are now based in the Bioscience Research Building, are currently investigating the cellular mechanisms involved in HGPS, which could hopefully also shed light on common diseases that could be linked with HGPS and regular aging, such as cardiovascular diseases, obesity and even Type II diabetes. "We want to look for more effective treatments for progeria based on what we know," she said. To this end, Cao's lab employs and integrates many diverse biological disciplines, including cellular and molecular biology, biochemistry, genomics and bioinformatics. Funding for her research comes from a variety of sources, including the NIH, the Progeria Research Foundation and the Maryland Stem Cell Research Commission.

While the move did not change her area of research, Cao has found herself tasked with a new job at the University of Maryland - she's now a teacher and a mentor. "The fun part is interacting with young students," Cao said. In her capacity as a mentor, Cao feels that certain traits are shared by most successful researchers and scientists. "I think you have to be smart, have a strong interest in science, and work hard...," Cao said. "Creativity...is also important." However, she explained that, despite said qualities, there are many pathways to being a good researcher. Above all, Cao emphasized the importance of staying interested in science.

For Cao, "the freedom...of pursuing the scientific questions that most interest me" excites and motivates her to continue inves- tigating cellular mechanisms in HGPS in the hopes of finding answers to the questions that could help the daily life and health of people everywhere.