WashU Medicine physician-scientists at Siteman Cancer Center developing new combination therapy to treat metastatic melanoma. By Stephanie Stemmler Published: October 28, 2026 Read time: 3 mins The approach could potentially treat multiple cancer types, researchers say WashU Medicine researchers at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, have developed a promising combination therapy for treating an aggressive form of melanoma. The early-phase research, led by George Ansstas, MD, David Y. Chen, MD, PhD, and Naresha Saligrama, PhD, appears in the Journal of Clinical Investigation. The new therapy combines two commercially available drugs, tailmogene laherparepvec (also known as T-VEC) and binimetinib to treat patients with NRAS-mutated melanoma, a type of melanoma that is highly aggressive and occurs in up to 25% of patients diagnosed with cutaneous melanoma. T-VEC, a genetically modified herpes virus, is already FDA-approved as a local therapy for the treatment of unresectable advanced melanoma. It was the first oncolytic virus therapy in the U.S. when it was approved in 2015. However, even though the modified virus can kill injected tumor cells, it doesn't produce a strong enough immune response throughout the body on its own. Binimetinib is a MEK inhibitor that blocks the activity of MEK1 and MEK2 proteins to treat patients with NRAS-mutated melanoma. Currently, binimetinib is approved only in patients with two different types of cancer, BRAF-mutated melanoma and BRAF-mutated non-small cell lung cancer. Early-phase research at Siteman investigated the use of T-VEC and binimetinib as a combination therapy in seven NRAS-mutated melanoma patients. Six patients achieved a complete response as compared to only two out of seven patients responding when treated with T-VEC alone. "T-VEC works by replicating in cancer cells, causing them to burst, thereby stimulating the body's immune response," Ansstas said. "We have found that by combining T-VEC with binimetinib, we induced an exceptional clinical response in a small cohort of patients diagnosed with NRAS-mutated melanoma who participated in our early-phase trial." The findings point toward binimetinib's role in amplifying T-VEC's ability to kickstart the immune system and broaden the overall effectiveness of the immune response in patients. "The fact that we already have two commercially available therapeutics means that we can escalate the speed at which we move from early phase into larger clinical trials to test the dual therapy," Ansstas said. Patients diagnosed with NRAS-mutated melanoma currently are given immunotherapy as a standard first-line treatment. Other options include targeted therapies to slow tumor growth and other combination therapies in clinical trials. Now that there have been promising results in the early trial conducted at Siteman, the WashU Medicine researchers say larger, multicenter studies are needed to validate the T-VEC/binimetinib combination as a new option for treatment of NRAS-mutated melanoma. "Once this observation is validated, we will expand our investigation to additional tumor types, as this mechanistic approach has the potential to be effective across multiple cancer types," Ansstas said.

College Transit Challenge kicks off Nov. 5 with Mascot Meetup. Travis Wood October 22, 2026 Five Area Colleges and Universities to Compete in Three-Day College Transit Challenge Five area colleges and universities are preparing to face off in the 2026 College Transit Challenge, a three-day, region-wide competition designed to show students and campus communities just how far public transit can take them. The challenge runs Thursday, Nov. 5, through Saturday, Nov. 7, and is hosted by Citizens for Modern Transit in partnership with the St. Clair County Transit District and Metro Transit. Mascot Meetup Kickoff Event - Thursday, Nov. 5 The competition begins with a Mascot Meetup at 3 p.m. on Thursday, Nov. 5, at the Grand MetroLink Station. Representatives and mascots from all five institutions will gather with students and regional transit partners for remarks about the importance of transit access and the Metro U-Pass, followed by a group photo and a MetroLink ride to a kickoff celebration at Cobblestone STL on Laclede's Landing. Bonus-point scavenger hunt missions will be revealed at the event, featuring food, drinks, goodie bags and prizes. Saint Louis University, WashU, the University of Missouri-St. Louis, Southwestern Illinois College and St. Louis Community College will compete for school bragging rights. Students, faculty, staff, alumni and supporters can register at www.CollegeTransitChallenge.com under their school and earn points by riding MetroLink and MetroBus, visiting destinations throughout the region, completing scavenger hunt-style missions and posting about their experience. "This year's expanded, three-day challenge gives participants more ways to ride, explore and compete on their own schedules," said Kimberly Cella, CEO of Citizens for Modern Transit. "Whether they take one 30-minute trip or spend all three days completing missions with friends, every ride and every point will help their school." Earn Points for Your School Registered participants will receive text messages with challenge updates. Transit trips will be tracked by text, and the online leaderboard will be updated daily. The winning school will be announced Monday, Nov. 9. Points can be earned by: * Registering and tracking MetroLink and MetroBus trips by text * Attending the kickoff event on Nov. 5 * Completing scavenger hunt-style missions * Posting about their transit experience during the challenge Possible scavenger hunt destinations include the Gateway Arch, Forest Park, the Delmar Loop, Downtown Belleville, City Foundry STL, St. Louis Union Station, Busch Stadium, Enterprise Center and Metro-accessible trails and greenways, including the MetroBikeLink. Location-specific questions or photo requirements will be used to verify completed missions. Participants can take part for 30 minutes or all three days, alone or with friends, before, between or after classes, and from anywhere on the Metro Transit system. Registered participants also can receive a "Public Transit" T-shirt in a color specific to their school, picked up on campus or at the mascot meetup on November 5, while supplies last. "Public transit connects these campuses to jobs, entertainment, parks, cultural destinations and one another," said Ken Sharkey, managing director of St. Clair County Transit District. "The College Transit Challenge makes that connection tangible and gives campus communities a fun reason to discover new places without a car." Students and staff who have not yet obtained a Metro U-Pass should check with their college or university about campus distribution. Additional challenge and point information, registration instructions and school-specific Metro U-Pass details are available at www.CollegeTransitChallenge.com.

A new tool lets scientists design the shape-shifting proteins that defy ordinary rules. WashU Medicine and Syracuse researchers built GOOSE, a tool for designing shape-shifting disordered proteins, and quickly created 2,300 new drought-response proteins for living yeast cells. October 17, 2026 4-6 minutes WashU Medicine and Syracuse researchers built GOOSE, a platform for designing intrinsically disordered proteins, and used it to make 2,300 drought-response proteins for yeast. Textbook images of proteins usually show them as neat, folded structures: coils and sheets locked into a precise three-dimensional shape that determines what each protein does. Predicting those shapes from a protein's sequence was one of biology's great challenges until artificial intelligence tools such as AlphaFold largely cracked it, work that shared the 2024 Nobel Prize in Chemistry. But many proteins do not fold into a single shape at all. Large stretches of them flail, twist and constantly rearrange. Researchers at WashU Medicine and Syracuse University have now built a tool to design these disordered proteins and work out what their sequences do. The study is published in Nature. The unruly majority. These regions, known as intrinsically disordered regions, are far from rare. According to the release, about 70 percent of human proteins contain them. They are especially common in proteins that relay signals, regulate genes and help organize the cell's interior, and they have been implicated in diseases including cancer and neurodegeneration. Tau and alpha-synuclein, proteins that clump in the brains of people with Alzheimer's and Parkinson's disease, are both largely disordered. Their lack of fixed structure makes them hard to study and harder to design. Most protein design tools, including those that have produced new enzymes and vaccine components, are built around stable, folded shapes. That flexibility is often the point. Disordered regions can bind many different partners, switch between states quickly and help proteins gather into droplet-like compartments inside cells, known as biomolecular condensates. Those properties make them central to signaling, but also hard to capture with methods built around fixed structures. "The way people would typically try to study and design stable, folded proteins doesn't really work very well for disordered proteins," said Alex Holehouse, PhD, an associate professor of biochemistry and molecular biophysics at WashU Medicine. He and his colleague Ryan Emenecker, PhD, have spent almost five years pursuing an alternative. Building with sequence blocks. Rather than designing a fixed shape, the team's approach works at the level of sequence, treating a disordered region as a string of components whose makeup shapes how it behaves and what it can interact with, even without a stable structure. The tool, called GOOSE, draws on a library of sequence building blocks linked to particular cellular functions and uses them to generate blueprints for disordered proteins. Those designs can then be built in genetically engineered cells and tested. Researchers can add or remove building blocks to see how each one affects what the protein does. "The ability to design disordered proteins at a large scale with our platform now allows us to learn how their component sequences affect the cell, and it gives us a lens through which we can learn how naturally occurring changes in these proteins might drive diseases like cancer," said Emenecker, a faculty instructor in biochemistry and molecular biophysics and the tool's lead developer. Proteins to survive drought. To show what GOOSE can do, the team turned to yeast. Some disordered proteins help cells survive drying out, a property that matters for organisms from microbes to plants. The researchers used the platform to generate a large set of new designs. "We were able to very quickly design 2,300 different proteins that would respond to drought conditions in yeast," Emenecker said. According to the release, many of the designs worked as intended, helping yeast cells recover after drying, and many outperformed natural yeast proteins. The release does not report how many were tested or what share succeeded. The work feeds into a National Science Foundation-funded effort to develop crops that are more resilient to environmental stress. Emenecker sees broader possibilities. "This opens the possibility of being able to make new sensors that are sensitive to things outside what natural sequences would be attuned to, like toxins or cell damage," he said. "It has the potential to be very valuable." A target in cancer therapy. One of the team's main goals lies in cancer treatment. CAR-T cell therapy, first approved in the United States in 2017, reprograms a patient's own immune T cells to recognize and attack cancer. It has produced dramatic remissions in some blood cancers, but it does not work for everyone, can cause serious side effects and has had limited success against solid tumors. A key protein on the surface of CAR-T cells includes a disordered region that controls how strongly the cell responds when it finds its target. Efforts to improve it have so far relied largely on trial and error. Holehouse, a research member of Siteman Cancer Center, and Emenecker have received a Siteman grant to apply their tools to the problem. "With our technique, we can design better versions of these disordered regions to do the signaling in different ways," Holehouse said. "The hope is we won't be limited by the types of constraints that are currently hurting the efficacy of CAR-T therapies. That's a very concrete place where these tools can move medicine forward." Next steps. The CAR-T work is a goal rather than a result, and the release reports no experimental findings for it. Nor does it discuss limitations of the approach. Designing a sequence with the right overall properties is not the same as predicting every interaction a disordered protein will make inside a living cell, and testing designs at scale remains essential. Still, the ability to design disordered proteins systematically, rather than one at a time, opens a large and long-neglected part of biology to engineering. The research was supported by multiple National Science Foundation awards, the Human Frontier Science Program, the National Institutes of Health, the Alfred P. Sloan Foundation and Syracuse University. Notes. * "Rational design of disordered proteins for sequence-function investigation." Nature, 29 July 2026. DOI: 10.1038/s41586-026-10849-1. * WashU Medicine. "Finding order in the inner chaos of our cells." EurekAlert!, 29 July 2026. https://www.eurekalert.org/news-releases/1137643. Featured image: File image of a protein complex structure. Credit: Thomas Splettstoesser