Every cell in the human body has the same genomic DNA, or basic genetic program. But modifications to this program, called epigenetics, are what differentiate cells that have different functions, like brain cells and muscle cells, for example. Epigenetic changes also lie at the heart of some cancers, particularly their ability to resist cancer therapies.
Biophysicist Tao Wu, at Baylor College of Medicine, is studying how epigenetics could be exploited to treat cancer. He was recruited in 2018 from Yale Stem Cell Center, where he was an associate research scientist, with the help of a First-Time Tenure-Track Award from CPRIT. He joined the department of molecular and human genetics, and is associated with the cancer center, aging center, and the Therapeutic Innovation Center (THINC).
“I call cancer cells ‘the transformers,’” Wu says. “When you try to target or kill them, they will transform from fast-proliferating cells to become slow-proliferating, or they will become dormant, or ‘sleep,’ and just avoid the drugs you are using to try to kill them.”
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Every cell in the human body has the same genomic DNA, or basic genetic program. But modifications to this program, called epigenetics, are what differentiate cells that have different functions, like brain cells and muscle cells, for example. Epigenetic changes also lie at the heart of some cancers, particularly their ability to resist cancer therapies.
Biophysicist Tao Wu, at Baylor College of Medicine, is studying how epigenetics could be exploited to treat cancer. He was recruited in 2018 from Yale Stem Cell Center, where he was an associate research scientist, with the help of a First-Time Tenure-Track Award from CPRIT. He joined the department of molecular and human genetics, and is associated with the cancer center, aging center, and the Therapeutic Innovation Center (THINC).
“I call cancer cells ‘the transformers,’” Wu says. “When you try to target or kill them, they will transform from fast-proliferating cells to become slow-proliferating, or they will become dormant, or ‘sleep,’ and just avoid the drugs you are using to try to kill them.”
Some cancers are particularly adept. Glioblastoma, one of the deadliest brain cancers, and melanoma, a type of skin cancer, both “hide” from chemotherapy drugs. Wu wants to figure how this happens at the epigenetic level. If he can interfere with their transformation he could potentially make these cells more vulnerable to existing chemotherapy.
Pediatric cancers are another focus. Because the DNA in childhood cancers has not had time to accumulate genetic mutations that cause cancers in adults, these cancers typically arise from epigenetic errors. Learning more about epigenetic mechanisms that cause cancers in children could lead to more effective therapies.
So far, Wu has discovered that cancer cells utilize a unique stress response mechanism, an epigenetic change that adds a small chemical group to one of the DNA bases.
A growing glioblastoma tumor in the brain has some areas that that have less oxygen, particularly in the central part of the tumor. “In that microenvironment,” Wu says, “the cancer stem-like cells can survive, but all the other cells die.” When he mimicked the low-oxygen condition in incubated cells, he found that the stress response increased, so it appears to play a role in helping cells survive oxygen deprivation.
He also found the enzyme responsible for adding the chemical group, known as ALKBH1, and knocked out the gene that codes for it to see what would happen. He found that so-called “knockout” glioblastoma cells were no longer capable of forming tumors. He’s currently screening small molecules that could interfere with the function of ALKBH1, which in theory could help abolish a glioblastoma tumor, or at least keep it from evolving resistance to chemotherapy.
Wu is excited to have access to a high-throughput drug screening center at Baylor. Having a large startup fund from CPRIT allowed him to jumpstart his high-risk high-reward research. “CPRIT not only funds basic research, but if we get a patent they will help us build our own company,” he says, which was an especially attractive lure for him, he says.
Wu received his undergraduate degree in biophysics from Nankai University, in China, and his Ph.D. in genomics, bioinformatics, & systems biology from the Institute of Biophysics at the Chinese Academy of Sciences. He joined Yale in 2010 as a postdoctoral associate in genetics and became an associate research scientist in genetics at the Yale Stem Cell Center in 2014.
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