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When asked what comes to mind when the word “sugar” is used in a medical sense, most people will answer “diet” or “diabetes.” Only a few medical scientists – mostly glycobiologists – will answer “new treatment approaches” or even “disease prevention.” And yet, it has been known from the early days of biology and biochemistry that the cells in our body are not just made up of DNA, RNA, proteins and lipids (or fats), but also a lot of sugars.
“Every cell has a unique sugar coating,” said Robert Sackstein, MD, PhD, a bone marrow transplant physician and member of the BWH Department of Dermatology. “In fact, the sugar coat is a more distinguishing feature of a cell than its protein coat.”
Sackstein explained that defining the structure of these cell surface sugars is challenging because they are highly branched and thus more complicated in make-up than linear molecules such as proteins and DNA. But studies have recognized that sugar molecules attached to proteins and lipids at the cell surface play a crucial role in the control of cell-cell interaction.
“Importantly, surface sugars guide the migration of cells in the bloodstream, and also direct interactions between cells and their environment that are essential for normal cell and tissue development, and physiological function,” he said.
Sackstein’s lab was recently granted a prestigious Program of Excellence Award from the National Heart, Lung, and Blood Institute of the National Institutes of Health to support further investigations in glycobiology, the discipline which studies how sugars direct biologic processes. The Program of Excellence in Glycosciences Award is one of only five bestowed nationwide, and provides more than $17 million of funding to support research in the lab of Sackstein and his collaborators – Karin Hoffmeister, MD, of BWH; Joseph Lau, PhD, of Roswell Park Cancer Institute; and Vernon Reinhold, PhD, of the University of New Hampshire.
Their goal is to analyze certain sugars displayed on blood-forming cells, understand how they function to direct blood cell development and learn how to control them. That way, physicians and scientists will eventually be able to manipulate the expression of the target sugars to improve blood cell development or combat blood diseases such as leukemia.
In related work, Sackstein’s lab has developed a method to custom-modify the sugar coat of cells, a technique that may be used to direct migration of blood-borne cells to sites where they are most needed. “We eventually hope to be able to direct cellular trafficking depending on the clinical condition of the patient,” Sackstein said.
Sackstein’s lab has already made significant findings. “We have discovered that we can make stems cells migrate specifically to sites of tissue injury,” Sackstein noted. “We are cautiously optimistic that we will eventually have the ability to introduce sugar-engineered stem cells directly into the bloodstream, where they will then distribute on their own and repair the damaged tissues.”
This will be especially useful in situations where it is not feasible to inject stem cells directly into the site, such as the lungs in pulmonary conditions, the pancreas in diabetes, or in stem cell-based treatment of diseases involving multiple sites in the body at the same time, such as multiple sclerosis, osteoporosis and inflammatory bowel disease.
Beyond funding critical research objectives, the Program of Excellence in Glycosciences Award also provides Sackstein and his colleagues with an unprecedented opportunity to grow the field of glycobiology research by establishing a center for training investigators. This is the first center of its kind in the northeastern United States.
“Strides in glycobiology have already greatly impacted health care and will make even greater contributions in the years to come,” he said. “We want to be able to provide our colleagues – both research and clinical – with the expertise and tools to enable them to understand and apply the principles of sugar-based therapeutics.”