Friday, December 7, 2012

Telomeres are stretches of DNA at the ends of chromosomes. These specialized structures provide stability to our DNA molecules, make it possible for cells to divide, and hold secrets to how we age and get cancer.

Telomeres have been compared to the plastic tips on shoelaces, because they protect our genetic information.  In recent years, shortened telomeres have been associated with a variety of diseases, cancer, and even death.

Senthilkumar Perumal Kuppusamy, who earned his Ph.D. in the University of Iowa’s Interdisciplinary Graduate Program in Human Toxicology in 2012, observed that telomeres become shorter in cells treated with polychlorinated biphenyls (PCBs), which may result in premature aging and an increased risk of cancer.

Kuppusamy carried out experiments using a synthetic mixture of PCBs—created by UI human toxicology faculty member Hans-Joachim Lehmler—that resembles the PCBs in Chicago air. Kuppusamy also studied the effects of pure synthetic congeners, like PCB126, a dioxin-like PCB and a Group 1 carcinogen. The International Agency for Research on Cancer has classified PCB126 as directly involved in causing cancer in humans.

“We designed the experiments with long-term exposures to simulate the chronic exposure of humans who reside in PCB contaminated areas like Chicago,” Kuppusamy says. “We exposed human skin cells to PCBs for three months, and we demonstrated that the Chicago air mixture is shortening the telomeres. This indicates that a similar effect could be expected in humans when you’re exposed to PCBs for a long period of time.”

Gabriele Ludewig, faculty member in human toxicology and Kuppusamy’s mentor, indicates that the average person is likely to have  a much lower exposure to PCBs than her student used in cell culture. But his finding is very significant.

“We are not mimicking lifetime exposure, but this is the first time that anyone observed that the PCBs are shortening telomeres,” Ludewig says. “That was not known and toxicology hasn’t looked at the effects of toxins on telomeres very much. We are trying to make the research community aware of this issue. Now, the next task is to elucidate the mechanism that underlies this effect.”

Every time normal human cells divide, their telomeres become shorter. When telomeres are very short, cells essentially die, or these short telomeres become sticky, creating a chromosome imbalance in new cells.

“When the telomeres get too short, the cell no longer can divide and becomes inactive or dies,” Ludewig says. “The process is associated with aging, cancer, and a higher risk of death.”

The Iowa Experience

A native of India, Kuppusamy’s heart pushed him to the University of Iowa.

“I heard that the Midwest is a great place and a few of my senior researchers back in India said great things about the University of Iowa,” Kuppusamy says.

Kuppusamy enjoys interdisciplinary research. His research focuses on creating a toxicity profile of PCBs and determining if and how they cause cancer in humans.  After graduating in spring 2012, he worked for a few months as a research associate in Ludewig’s laboratory.

In September, Kuppusamy began working for the U.S. Environmental Protection Agency (EPA) in Cincinnati, where he does risk assessment of various environmental pollutants. He is applying the knowledge and skills that he obtained at the UI to make scientifically-based statements about the dangers of compounds humans may be exposed to.  

While studying at Iowa, Kuppusamy received numerous awards from scientific organizations, including Best Graduate Student Abstract Awards from the Risk Assessment Specialty Section (2010) and the Dermal Toxicology Specialty Section (2011) of the Society of Toxicology (SOT). In 2010 and 2011, he also earned the Alexander Hollaender Travel Award from the Environmental Mutagen Society (EMS). These prestigious merit-based awards recognized the excellence of his research progress and promise as a long-term contributor to research in environmental mutagenesis.

Additionally, Kuppusamy served in several student leadership roles in scientific societies, including the SOT and EMS. He also was the human toxicology representative on the UI Graduate Student Senate (GSS), and was elected to represent GSS on the Executive Council of Graduate and Professional Students (ECGPS). ECGPS is composed of six member governments from each degree-granting college at the University of Iowa and represents the over 9,000 UI graduate and professional students.  

“The Graduate College did a really great job supporting the Human Toxicology Program and its students. (Graduate College Dean John) Keller is so supportive of everything,” Kuppusamy says. “I am proud to call myself a UI alum and a Hawkeye. Iowa has become part of me. I will always support the University of Iowa in any way I can.”