A Protein that Can Melt Tumors Discovered

For the second time, cancer researchers at Vanderbilt have discovered a protein that—when genetically manipulated to impede it from interacting with a gene responsible for cancer genesis—effectively melts tumors in days. 

William Tansey, professor of cell and developmental biology, is dedicated to understanding how the oncogene MYC, an  highly conserved, noodle-like protein, works. It performs important functions in normal human development, and it often becomes reactivated in the deadliest and most difficult to treat cancers. 

Conducted experiment shows six tumor sizes grow for 15 days, at which point the MYC–HCF1 interaction is broken. After day 15, the tumors shrink and are gone. Cancer cells are dead by four days. 

MYC becomes the nitro in the tank, driving relentless rounds of cell duplication and division,” Tansey said. “The faster the cells grow and divide, they accumulate mutations, which give rise to cancer growth.” 

MYC has been an elusive drug target for at least 30 years, Tansey says, and has been considered “undruggable” because of its lack of structure. To work around this roadblock, Tansey set out to identify MYC’s more structured partner proteins with the goal of engineering mutations that disrupt the partners’ interactions with MYC that cause cancer growth. “If we can validate the physical contact between MYC and a protein, we can go after it therapeutically,” Tansey explained.  

Tansey and his collaborators have identified the protein Host Cell Factor-1 (HCF1) as a definite candidate for this type of therapeutic development. HCF1 is touched by MYC and is important for stimulating protein synthesis. When a cancer cell with MYC is genetically engineered to no longer interact with HCF1, the cancer cell begins to self-destruct. Developing a therapy that limits this interaction is a hugely promising step in cancer treatment 

The article, “MYC regulates ribosome biogenesis and mitochondrial gene expression programs through interaction with Host Cell Factor-1,” was published in the journal eLIFE on Jan. 8. 

Source: https://news.vanderbilt.edu/

Exoskeletons Assist Individuals With Spinal Cord Injury

(from Inverse.com) Green Lantern’s ring, Wonder Woman’s bracelets, Captain America’s shield, and, of course, Batman’s batsuit:  30 years later, as National Superhero Day approaches, I’d be designing components of my own supersuits.

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I didn’t really notice this until a few months ago. On that day, my childhood dreams were at once destroyed and fulfilled. Standing in a line, I noticed that everyone was focused on their smartphones’ screens. Suddenly it hit me: I already had Sword of Omens superpowers. With my smartphone, I can see video of faraway events and text my friends to meet up. Billions of people now have what used to be considered superpowers.

But what about the physical superpowers? I wanted those, too — like superhuman endurance or strength. Those may not be too far behind. I’m working on them in Vanderbilt’s Center for Rehabilitation Engineering and Assistive Technology. Humanity has begun to enter the age of wearable exoskeletons and exosuits thatoffer support and strength to people’s bodies. Over the past five years, wearable exoskeletons that assist and aid movement have begun to shift out of research labs and into public use. They’re still early versions, and the science is still emerging, but they include the first of several FDA-approved exoskeletons to assist individuals with spinal cord injury or after stroke, as well as exoskeletons to help keep workers safe and reduce the fatigue of physically demanding jobs.

Source: https://engineering.vanderbilt.edu/
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https://www.inverse.com/

Nanoparticle Targets Tumor-infiltrating Immune Cells, Flips Switch Telling Them To Fight

Immunotherapy’s promise in the fight against cancer drew international attention after two scientists won a Nobel Prize this year for unleashing the ability of the immune system to eliminate tumor cells.

But their approach, which keeps cancer cells from shutting off the immune system’s powerful T-cells before they can fight tumors, is just one way to use the body’s natural defenses against deadly disease. A team of Vanderbilt University bioengineers today announced a major breakthrough in another: penetrating tumor-infiltrating immune cells and flipping on a switch that tells them to start fighting. The team designed a nanoscale particle to do that and found early success using it on human melanoma tissue.

Tumors are pretty conniving and have evolved many ways to evade detection from our immune system,” said John T. Wilson, assistant professor of chemical and biomolecular engineering and biomedical engineering. “Our goal is to rearm the immune system with the tools it needs to destroy cancer cells. “Checkpoint blockade has been a major breakthrough, but despite the huge impact it continues to have, we also know that there are a lot of patients who don’t respond to these therapies. We’ve developed a nanoparticle to find tumors and deliver a specific type of molecule that’s produced naturally by our bodies to fight off cancer.

That molecule is called cGAMP, and it’s the primary way to switch on what’s known as the stimulator of interferon genes (STING) pathway: a natural mechanism the body uses to mount an immune response that can fight viruses or bacteria or clear out malignant cells. Wilson said his team’s nanoparticle delivers cGAMP in a way that jump-starts the immune response inside the tumor, resulting in the generation of T-cells that can destroy the tumor from the inside and also improve responses to checkpoint blockade.

While the Vanderbilt team’s research focused on melanoma, their work also indicates that this could impact treatment of many cancers, Wilson said, including breast, kidney, head and neck, neuroblastoma, colorectal and lung cancer.

The findings are reported in the journal Nature Nanotechnology.

Source: https://news.vanderbilt.edu/