Grant for Cancer Research

Assistant professors receive combined funding in excess of $1 million from American Cancer Society

Two faculty members within the UT College of Pharmacy have been notified that they are recipients of significant research grants from the American Cancer Society. The two grants, which are independent of one another, generated combined support in excess of $1 million from the Cancer Society.

Funding for the grants begins in January 2005 and continues over the next four years.
Shawn Bratton, assistant professor of pharmacology, received a total of $720,000 to support his study of apoptosis or programmed cell death, a naturally occurring process in which a cell determines that it cannot survives and consequently kills itself through a systematic process.

The researcher explained that apoptosis is a means for the body to rid itself of injured cells within a tissue, without causing inflammation. When apoptosis does not work properly, disease often results either due to the inhibition of apoptosis (cancers and autoimmune diseases) or through increased rates of apoptosis (AIDS, Alzheimer’s Disease, Parkinson’s Disease, stroke and heart disease).

Dr. Batton explains that apoptosis is regulated in the body by the activation of cysteinyl aspartate-specific proteases, or caspases. There are a number of important caspases in the cell, but Dr. Bratton’s laboratory is focused on caspase-9, which is thought to play a critical role in apoptosis induced by chemotherapeutic agents and environmental toxicants. Bratton’s lab is working to understand how inhibitor-of-apoptosis (IAP) proteins and their antagonists regulate caspase-9 activity.

“Basically IAPs are direct inhibitors of caspase-9, but there are also inhibitors of IAPs in the cell” he said. “If we can better understand how these IAP antagonists function, we can work to develop drugs that mimic these secondary inhibitors and, in turn, might help treat cancer by promoting caspase-9 activity.”

Dr. Bratton earned his Ph.D. at UT Austin.

Walter Fast, assistant professor of medicinal chemistry, also received $720,000 to support his study of a process that permits tumor cells to grow, particularly the role of an enzyme known as dimethylarginine dimethalaminohydrolase or DDAH.

Dr. Fast explains that humans produce a substance known as nitric oxide that is often referred to as a double-edged sword for its ability to promote or impede the development of cancer cells depending upon the levels of its concentration.

At high levels, nitric oxide aids in natural immunity and induces natural cell death in cancerous tissues. However, when nitric oxide is chronically produced at lower concentrations by its biosynthetic enzyme, nitric oxide synthase, it can actually promote tumor growth and may lead to DNA damage. For example, low levels of nitric oxide production have been detected in malignant human breast, neuronal, gastric, cervical and ovarian cancer, but not in the surrounding benign tissues.

In humans, nitric oxide synthase activity is partially regulated by naturally occurring substances known as methylated arginine amino acids. Although it is known that the DDAH enzyme can control the concentrations of these amino acids, Dr. Fast notes that the process by which this happens has not been fully investigated.

His lab will use purified DDAH to study, in detail, the chemistry of how this enzyme works, how it can be regulated by both reactive oxygen species and by synthetic compounds, and how it can be re-engineered for use in anti-tumor therapy. Other aspects of his project are supported by research grants from the American Heart Association, the Welch Foundation, and a UT undergraduate research fellowship.

Understanding these fundamental processes, Dr. Fast believes, will allow scientists to learn more about the role that DDAH plays in cancer biology and may eventually lead to new therapeutic treatments.

Dr. Fast and Dr. Bratton joined the College faculty in August 2002.