The University of Seoul

Researchers have zeroed in on specific mechanisms that activate oncogenes, which are altered genes that can cause normal cells to become cancer cells. This work advances the ability to predict and interpret which genetic mutations found in cancer genomes are causing the disease. Cancer, caused by abnormal overgrowth of cells, is the second-leading cause of death in the world. Researchers from the Salk Institute have zeroed in on specific mechanisms that activate oncogenes, which are altered genes that can cause normal cells to become cancer cells. Cancer can be caused by genetic mutations, yet the impact of specific types such as structural variants that break and rejoin DNA, can vary widely. The findings, published in Nature on December 7, 2022, show that the activity of those mutations depends on the distance between a particular gene and the sequences that regulate the gene, as well as on the level of activity of the regulatory sequences involved. This work advances the ability to predict and interpret which genetic mutations found in cancer genomes are causing the disease. "If we can better understand why a person has cancer, and what particular genetic mutations are driving it, we can better assess risk and pursue new treatments," says Salk physician-scientist Jesse Dixon, senior author of the paper and an assistant professor in the Gene Expression Laboratory. Most genetic mutations have no impact on a cancer and the molecular incidents that lead to oncogene activation are relatively rare. Dixon's lab studies how genomes are organized in 3D space and seeks to understand why these changes happen in some, but not the majority, of circumstances. The team also wants to identify factors that might distinguish where and when these events occur. "A gene is like a light and what regulates it are like the light switches," says Dixon. "We are seeing that, because of structural variants in cancer genomes, there are a lot of switches that can potentially turn 'on' a particular gene." Using CRISPR-Cas9 gene editing, the research team introduced genetic mutations by cutting DNA in certain locations of the genome. They found that some of the variants they created had major impacts on the expression of nearby genes, and could ultimately cause cancer, but that most had essentially no impact. Some genes appeared to go haywire when they were brought into environments with novel regulatory sequences, and others were not affected at all. The type of sequence that was introduced appeared to have a huge impact on whether or not the cell became cancerous. "Our next move is to test whether there are other factors in the genome that contribute to the activation of oncogenes," says Zhichao Xu, a postdoctoral fellow at Salk and the paper's co-first author. "We are also excited about a new CRISPR genome editing technology we are developing to make this type of genome engineering work much more efficient." Other authors on the study are Sahaana Chandran, Victoria T. Le, Rosalind Bump, Jean Yasis, Sofia Dallarda, Samantha Marcotte, Benjamin Clock, Nicholas Haghani, Chae Yun Cho, Selene Tyndale, Graham McVicker, and Geoffrey M. Wahl of Salk; Dong-Sung Lee of the University of Seoul, South Korea; and Kadir Akdemir and P. Andrew Futreal of the University of Texas MD Anderson Cancer Center. The research was supported by the National Institutes of Health (DP5OD023071), the Leona M. and Harry B. Helmsley Charitable Trust (2017-PG-MED001), the National Institutes of Health National Cancer Institute (R35 CA197687), and the Breast Cancer Research Foundation.

If you haven’t already had laser eye surgery, odds are pretty good you will at some time in the future. A Korean-U.S.academic collaboration recently announced new technology that has the potential to improve laser surgery precision significantly. We’ve written before about synthetic soft tissue retinal implants, injectable lenses, and LCDs replacing human eye lenses. We’ve not previously covered laser eye surgery, a technology that was a giant leap ahead in ophthalmic surgical potentials. The excimer laser was not approved by the FDA for corrective eye surgery until 1995, although it was developed in the early 1970s and used in Russia for radical keratotomy (RK) throughout the 70s. Researchers at the Korea Institute of Science and Technology (KIST), the University of Seoul in Korea, and Drexel University collaborated on technology that pulses stable laser light for just 600 femtoseconds (quadrillionths of a second). The scientists worked with MXenes, a class of composite materials created by combining carbon and/or nitrogen with transition metals from the middle of the periodic table. MXenes are already used in energy storage and gas-sensing applications but had not previously been studied for ultrafast optics applications. Skipping ahead of a lot more science to get to the health tech part, the collaborative team placed a device composed of titanium carbonitride MXene in a laser and discovered its ability to produce stable yet very short laser pulses that are femtoseconds — or millionths of billionths of a second — long. The big deal here isn’t just the speed. A femtosecond is a million times shorter than a picosecond, which is one-millionth of a millionth of a second. By adding stability to femtosecond speed pulses, the Korean and U.S. researchers open the possibility for eye surgery. The group study was published in the journal Advanced Materials. Lasers cut or destroy by burning, that’s their job. Laser pulse speed control is a major factor in living tissue; if a laser pulse lasts too long, it risks the heat spreading and destroying more than just the target. If the pulse targeting is not exact, the prospect of a powerful cutting and burning tool bouncing around inside a human eye is a nonstarter. If your eye doctor told you they were going to use a laser that made very fast, tiny cuts in your eye to improve or repair your vision, any positive feelings you might have about the prospect would fade instantly if they added, “Of course, we do have to disclose that the laser is sometimes not all that stable, so there’s a risk.” By adding stability to femtosecond laser pulses, the element of control plus speed increases the chances of your future laser eye surgery resulting in better vision than you’ve ever had before.