Lin Zhang, PhD

Apoptosis, or programmed cell death, is a normal suicidal process the body uses to selectively remove cells that are no longer needed, damaged or dangerous. Apoptosis is fundamental to our health; failure of cells to die leads to initiation and progression of cancer, and makes cancer cells resistant to anticancer drugs.

With his Career Investigator Award, Dr. Zhang was able to identify PUMA, a novel controller of apoptosis and a target of p53, the gene that is altered in the majority of lung tumors. He found that PUMA is important in apoptosis induced by a variety of types of anticancer drugs—not just conventional chemotherapy drugs, but also the more recent targeted therapies, such as erlotinib (Tarceva) and cetuximab (Erbitux), which have been used for treating lung cancer patients. However, he also noted that PUMA is frequently interrupted in lung cancer cells due to abnormalities of p53.

He then studied the effect of a virus that produces PUMA, called Ad-PUMA, on lung cancer cell growth. When lung cancer cells were infected with Ad-PUMA, their growth was inhibited. A low dose of Ad-PUMA significantly sensitized lung cancer cells to anti-cancer treatments by inducing apoptosis. He also found Ad-PUMA combined with the cancer drug cisplatin was much more effective in killing lung cancer cells compared with cisplatin alone. Finally, Dr. Zhang developed a new screening method that can be used to distinguish anticancer agents that can induce PUMA from those that cannot. Dr. Zhang plans to use this new screening method to identify novel compounds that stimulate PUMA to induce apoptosis in lung cancer cells that are deficient in p53.