Genes are the blueprints for making human cells, but since every cell has the same blueprint, how do muscle cells end up looking and functioning differently from brain cells? Scientists have discovered regions of the genome called “enhancers” that often determine which genes are going to be expressed in each cell type.
Disruptions or mutations in these regulatory systems can lead to cancer. Now a molecular biologist at McGovern School of Medicine of the University of Texas at Houston hopes to better illuminate the role of these cellular remote-control switches, in order to figure out ways to control them when things go haywire.
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Genes are the blueprints for making human cells, but since every cell has the same blueprint, how do muscle cells end up looking and functioning differently from brain cells? Scientists have discovered regions of the genome called “enhancers” that often determine which genes are going to be expressed in each cell type.
Disruptions or mutations in these regulatory systems can lead to cancer. Now a molecular biologist at McGovern School of Medicine of the University of Texas at Houston hopes to better illuminate the role of these cellular remote-control switches, in order to figure out ways to control them when things go haywire.
Wenbo Li, who was a postdoctoral fellow at the University of California, San Diego, was recruited in 2017 with the help of a First-Time Tenure-Track Award from CPRIT.
Hundreds of thousands of enhancers exist in the human body, but how they determine which genes are expressed is something scientists don’t yet fully understand. The DNA of human genes is translated to RNA, which then codes for proteins that make up the structure and function of cells. Enhancers, on the other hand, are translated to RNA, but don’t go on to make proteins, instead serving other functions like turning on and off other genes.
Some “enhancer RNAs” are only found in certain tissues and cells, and cancer types also contain specific enhancer RNAs. For example, lung cancer cells have different enhancer RNAs than breast cancer cells, and even among individual patients with the same type of cancer, a variety of specific enhancer RNAs might be found.
Enhancer RNAs may play a role in helping cancers develop resistance to therapy, Li says. About 70 percent of breast cancers need the hormone estrogen in order to grow and proliferate, so inhibiting estrogen’s action in a woman’s body can be a good therapy — at least initially. But at least half of these patients eventually develop resistance, and the cancer proliferates even without estrogen.
Li thinks enhancer RNAs play a significant role in reprogramming these cancer cells to grow under changing conditions. He plans to screen for differences in enhancer RNA profiles between cancers that are sensitive or resistant to anti-estrogen therapy in order to find out which enhancer RNAs are most significant. He also hopes to develop inhibitors that would knock out enhancer RNAs that facilitate resistance.
Currently he is studying mouse models of breast cancer as well as patient-derived breast cancer tumors grown in mice. He thinks he could potentially inhibit a cancer-causing enhancer by using specifically designed chains of nucleotides—material similar to what makes up RNA—that would bind directly to a particular enhancer and take it out of action.
“Initially, genomics will give us a set of target enhancer RNAs at the level of cancer type,” Li says. “But each individual patient is different, and eventually we hope to develop a pre-defined target enhancer RNA for each individual, to achieve personalized cancer medicine. This is a little far down the road, but it’s surely achievable.”
Li says the support from CPRIT will allow him to achieve his goals much faster and make progress in a shorter period of time. “CPRIT also allows us to have a chance to interact with cancer researchers in the state and around the country,” he says. “I’m also an educator and science advocate, not just a scientist,” Li says. “I am happy to spread the knowledge we gain from research to society.”
Li was an undergraduate in biotechnology at Zhejiang University in China, and received his Ph.D. in neuroscience from the National University of Singapore. He came to the U.S. as a postdoctoral researcher at UCSD in 2010.
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