Since the late 1990s, Paul K.Y. Wong, PhD, from the University of Texas MD Anderson Cancer Center has been exploring what goes wrong in blood and brain cells when the A-T protein is missing. Although A-T is not the primary research focus for Dr. Wong, a leading investigator in the area of mouse retroviruses as a model for HIV associated dementia, his laboratory has produced more than 10 A-T related papers in the past decade.
Previously, Dr. Wong’s lab explored the development of the aggressive thymic lymphoma that occurs in A-T mice, as well as methods to prevent it. His lab also found that oxidative stress exists in blood cells from these mice. More recently, Dr. Wong and his team demonstrated that oxidative stress-mediated growth defects exist in neural stem cells and astrocytes from A-T mice.
Neural stem cells give rise to the two types of mature brain cells, neurons and glia. Astrocytes are a special type of glia that support, signal to and influence the metabolism and activities of neurons. Lack of ATM protein leads to abnormally high levels of free radicals in brain cells, which results in chronic oxidative stress and the activation of specific downstream signaling pathways. These abnormalities in A-T mouse brain cells may, at least in part, explain the neurodegeneration associated with A-T in humans. In addition, Dr. Wong’s translational research exploring these abnormalities may one day lead to potential therapies for individuals with A-T.
Over the years, Dr. Wong’s A-T related research has been supported exclusively by the MD Anderson Cancer Center and disease advocacy organizations like the A-T Children’s Project.