The Twists and Turns of a Stomach Cancer Bug
Nina Salama, Microbiologist
Microbiologist Nina Salama, PhD, who holds the Dr. Penny E. Petersen Memorial Chair for Lymphoma Research, has long been fascinated by bacteria, but as a young researcher looking to branch out from basic biochemistry to study the bugs that make us sick, she never dreamed she’d one day play a major role in cancer research.
Then, at the start of her postdoctoral fellowship, she learned about a study that strongly linked the stomach bacteria Helicobacter pylori with gastric cancer, the third leading cancer killer worldwide.
“That was mind-boggling, that bacteria could cause cancer,” Salama said. “That captivated me and I thought, ‘Wow, I don’t know how I’m going to do it, but I’m going to study H. pylori.’”
Salama and her team in Fred Hutch's Human Biology Division are now leaders in the field studying that bug: how it colonizes the stomach, and how it triggers the chronic inflammation that can lead to gastric ulcers and, for some, stomach cancer. She is fascinated both by this pathogen’s unusual ability to survive in the stomach and why the bacterium triggers cancer in only a relatively small percentage of those infected.
She’s discovered that H. pylori’s unique corkscrew shape allows the bug to burrow into the stomach lining and survive that organ’s acidic environment. Her team found a set of eight key proteins responsible for the bug’s twisty form; H. pylori that are missing any of those proteins are rod- or crescent-shaped and cannot set up shop in the stomach. These proteins could therefore be possible drug targets to prevent or treat infection, Salama said.
“That was mind-boggling, that bacteria could cause cancer,” Salama said. “That captivated me and I thought, ‘Wow, I don’t know how I’m going to do it, but I’m going to study H. pylori.’”
Salama is also studying how other bugs in our body interact with H. pylori and whether that bacterial interplay could push an infected person toward developing gastric cancer.
And to help them untangle exactly how H. pylori contributes the tissue changes that precede stomach cancer, she and her team are capitalizing on a new preclinical model of the process.
After H. pylori infects the stomach, it causes inflammation that can prompt the lining of the stomach to undergo characteristic changes that raise a person’s risk of cancer. First the cells that secrete acid and those that release digestive enzymes are destroyed, and the stomach’s pH increases. Then the cells lining the stomach take on characteristics of the cells that line the intestine, a process called intestinal metaplasia.
“People with these metaplasias are at much higher risk for gastric cancer,” Salama said. “I’ve always been interested in how H. pylori interacts with metaplasias, but it’s very difficult to study.”
Using the new model, Salama’s team was able to show that the bacterium exacerbates and hastens the stomach’s metaplastic tissue changes. Now, they’re exploring whether H. pylori does more to promote cancer than maintain stomach inflammation, and how the bug itself adapts to the environmental changes it triggered.
Salama is also branching out: H. pylori is not the only bacteria that infects the stomach, and she is investigating whether other bacterial species contribute to the development of stomach cancer. It may be that H. pylori teams up with — or is replaced by — other bacteria at later stages of disease.
Salama said collaboration and a risk-taking culture have propelled her work at Fred Hutch. "Isolation really stifles creativity," she said. "But working together to blend creative approaches is encouraged here. I love that we're constantly getting reseeded with new ideas."
Taking chances and exploring unexpected research paths are the essence of good science, Salama said. "You have an idea to bring things together one way, but you don't know where things are going to go. Just starting the process is critical — if you never start, you'll never learn."
— By Rachel Tompa, updated Dec. 12, 2022
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