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Wistar Science Highlights: Linking Mutations and Telomeres to Cancer, AACR Annual Meeting, RNA Editing in Octopuses and Other Creatures

In the everchanging landscape of research discoveries, Wistar scientists are remaining at the forefront of science – from being published in notable journals, to providing expert commentary in national and international news outlets, to presenting research updates and speaking at a major international cancer research meeting among peers. Read more to learn about what has been happening at Wistar in our world of discovery science.

Scientists Reveal How Genetic Mutations in Key Protein Complex Promote Cancer Development

Telomeres are special structures that serve as the protective ends of our chromosomes, preserving our vital genetic information. Defects in their function can lead to cancer, while their gradual shortening is associated with aging. A protein complex called shelterin helps telomeres serve their protective function by regulating their maintenance and replication.

Emmanuel Skordalakes, Ph.D., associate professor in the Gene Expression and Regulation Program at Wistar, in his most recent research published in Nature Communications, focused on two subunits of the shelterin complex: POT1 and TPP1. In cancers like familial melanoma and chronic lymphocytic leukemia, POT1 has been affected by genetic mutations. Using structural, biochemical, and cell-based data, the Skordalakes lab wanted to show how these mutations may lead to the development of cancer.

Once the Skordalakes lab revealed the structure of these proteins, they found that some of the mutations could reduce the ability of these proteins to bind to telomeres, while others disrupted the structure of POT1. They also found that the mutations result in defects in telomere length and structure, putting chromosomes more at risk for abnormalities.

“Based on our data, we suggest that the cancer-associated mutations reported in POT1 affect the integrity of telomeres, leading to chromosomal abnormalities and in turn genomic instability, which is a hallmark of cancer progression,” Skordalakes said. “We think that this mechanism works in combination with other fundamental genetic defects characteristic of these malignancies.”

RNA Expert Comments on New Study About Octopuses Adapting to Environment

Coleoid cephalopods, a group of marine creatures that includes octopuses, squid and cuttlefish, are already known for their intelligence for an invertebrate species. Now, a new study in the journal Cell shows that these creatures use a process called RNA editing to diversify proteins in their nervous system. The scientists suggest that this may allow them to dynamically control their proteins in response to different environmental conditions or tasks.

Kazuko Nishikura, Ph.D., professor in the Gene Expression and Regulation program at Wistar, has done extensive research into RNA editing and its role in cancer development. Considered an expert in the field of RNA editing, Nishikura was interviewed by writers for The New York Times and The Atlantic about the significance of this new study.

Nishikura, who was not involved in the study, described the possibility of these creatures using RNA editing to manipulate their nervous systems as “extraordinary.” “I study RNA editing in mice and humans, where it’s very restricted,” she told The Atlantic. “The situation is very different here. I wonder if it has to do with their extremely developed brains.”

Click here to view the story from The New York Times. Click here to view the story from The Atlantic.

Wistar at the American Association for Cancer Research Annual Meeting

The American Association for Cancer Research (AACR) Annual Meeting was held in Washington, D.C., from April 1-5, and drew thousands of attendees with the aim of highlighting the best cancer science and medicine from institutions all over the world. During the meeting, several Wistar scientists were in attendance, with some making key presentations.

Dario Altieri, M.D., president and CEO of Wistar and the Robert and Penny Fox Distinguished Professor, discussed the research advances in the study of mitochondria and tumor onset and progression. Altieri and other researchers have demonstrated that tumor mitochondria are key drivers of cancer, and pathways involving mitochondria have been liked to aggressive disease and drug resistance, providing potential new therapeutic targets for cancer.

Meanwhile, David Weiner, Ph.D., Executive Vice President and Director of the Vaccine Center at Wistar and the W.W. Smith Charitable Trust Professor in Cancer Research, presented an overview of DNA vaccines and shared how they perform well when used as immune-based approaches for cancer treatment. He described how improvements in DNA vaccines led to a synthetic immune therapy for HPV, which showed very promising results in clinical trials.

In a separate session, Ashani Weeraratna, Ph.D., Ira Brind Associate Professor and program leader of the Tumor Microenvironment and Metastasis Program at Wistar, discussed resistance to melanoma therapy. She described the critical role that the tumor microenvironment plays in supporting and promoting changes associated with both therapy resistance and metastatic progression. These changes can affect everything from signaling pathways within the tumor cell to how the tumor is able to protect itself from cytotoxic drugs and spread to other organs. Weeraratna said that understanding the microenvironment is going to be crucial in the future design of therapies for cancer.