Glycans are a fundamental building block of life. New research seeks to better understand the essential role they play in the fight against diseases including cancer.
Glycobiology, the research field focused on understanding glycans (also known as carbohydrates or sugars), is an integral but understudied area. Glycans cover the surfaces of our bodies’ cells that affect how cells recognize each other, and they play an essential role in our bodies’ health. “The often overlooked glycans are one of the five building blocks of life,” said Versiti Blood Research Institute Senior Investigator Karin Hoffmeister, MD. “They are central to life—to human disease and health. Glycans are part of our ‘I.D.,’ a critical function that identifies us as ‘self and non-self’; for example, healthy cells vs. cancer cells.”
Glycans also play a critical role in the human body’s immune system. Immune cells communicate with the sugars on cells, including circulating blood cells and endothelial cells, which line the interior surface of blood vessels and help ensure the health of tissues and organs. But when a virus or bacteria enters the body, it invades our body’s cells and hijacks our glycosylation machinery and disguises itself with our “I.D. glycans,” becoming indistinguishable to the immune system. This means that the immune system no longer identifies them as foreign and doesn’t fight against them.
Unfortunately for the immune system, viruses and diseases are smart. They understand that the immune system is adaptable—and that glycans are the most versatile of all. Like viruses, cancer cells also hijack glycans to disguise themselves to the immune system. They figure out ways to manipulate the glycans on the surfaces of cells to continuously manipulate immune responses for their own advantage, enabling them to survive and spread throughout the body. Their ease of adaptation and their complex signatures have made studying glycans an overwhelming task for many researchers—but one that is no less important.
Dr. Hoffmeister is a leading expert in glycan research and is working hard to define the structures of glycans and identify if some glycans are specific to various disease states. With this knowledge, she and her peers will be better positioned to study how harmful viruses, cancer cells and other diseases continuously adapt and trick our bodies into thinking they belong. “Currently, our focus is on understanding two things: first, how glycans regulate blood production in normal conditions; and second, how glycans change when stressed, like during cancer or inflammation,” she said.
But glycans affect more than just the immune system and how it responds to disease and infection. They also affect blood cell production and even help determine someone’s blood group—A, B, AB or O—which is recognized by the immune system and is a well-recognized “I.D.” for blood transfusions and organ transplants. Understanding glycans’ structures and how they function will help investigators like Dr. Hoffmeister further their research and help more patients. “The ultimate goal is to find better diagnostics and treatments,” she said.
Since coming to Versiti Blood Research Institute (BRI), Dr. Hoffmeister has helped her colleagues realize that everything they study is tied to glycans. “They’re glycobiologists, but they don’t know it,” she said. “There’s a combined knowledge at the BRI, and that’s what glycobiology needs: to harness the knowledge of many different scientific areas, including immunology, hematopoiesis and stem cell biology—and that all exists here.”
In 2018, Dr. Hoffmeister was awarded nearly $5 million from the National Heart, Lung and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), to establish the Translational Glycomics Center at Versiti Blood Research Institute. The Center is part of the first NHLBI-established consortium of four sites to study glycobiology and encourage investigators to pursue careers in this research area. It offers a K12 career development program that supports and educates glycoscientists, helping them better understand glycans and the role they play in human health. “That’s what the center stands for: to cooperate, educate and develop projects in novel directions,” Dr. Hoffmeister said. “It’s an incredibly exciting field and I am happy to be able to contribute to it.”
Karin Hoffmeister, MD, is a senior investigator at Versiti Blood Research Institute and program director and primary mentor at the Translational Glycomics Center.