Versiti Blood Research Institute Articles

Versiti Investigator Published in Prestigious Scientific Journal Cell

March 30, 2023

Jieqing Zhu, PhD, was part of a team that studied cell receptors and how they can be used to develop new treatments for disease.

A lot goes into creating a new type of medicine, whether it’s something to dull a headache or a brand-new drug to treat cancer. Scientists conduct countless hours of clinical and laboratory research, during which they examine the body’s cells to understand their function, why they do what they do, and sometimes why they do things they shouldn’t.

A team of researchers from Harvard University Medical School and Versiti Blood Research Institute Senior Investigator Jieqing Zhu, PhD, were recently published in the prestigious scientific journal Cell for their work studying cell integrin receptors and how they can be better used to develop new therapies for bleeding and clotting disorders, inflammation, angiogenesis, tumor growth and metastasis, multiple sclerosis (MS), irritable bowel disease, nephritis, osteoporosis, sickle cell disease, and fibrosis.

Understanding integrin receptors

Integrin receptors are long-established treatment targets, with six approved therapeutics for treatment of multiple sclerosis, ulcerative colitis, dry eye disease and blood clots. Integrin receptors jump into action when they receive an internal signal and go into a ligand-binding state, when a molecule or atom irreversibly binds to a cell receptor and initiates different responses. Then, they transmit other signals back to the cell—an important process in human health and for the development of drugs to treat diseases. The problem is that some of the drugs that target integrin receptors may also initiate unwanted, potentially harmful physiological responses.

Evolution of research

Early research determined that peptides could block the ligand-binding mechanism and therefore prevent unwanted physiological responses. However, five phase III clinical trials failed, with high rates of mortality and some patients developing antibodies to the drug they were prescribed. Research was shut down, but over time, new information came to light about a new class of ligands that blocked receptor responses, rather than initiating them.

During their research to better understand this process, Dr. Zhu and the rest of the team hypothesized that they would be able to uncover a chemical principle that would enable a drug to bind to specific integrin receptors without turning on their signaling capabilities, and that this could be used on other integrin receptors that are potential targets for therapies.

Unlocking the answer

The key chemical compound to emerge was something relatively simple: water. By stabilizing a key water molecule, researchers were able to prevent integrin receptors from activating and sending unwanted signals. This marks a key turning point in the future of drug development, as researchers will be able to repurpose existing blockers for integrin receptor activation and use them to develop new drugs to treat autoimmune diseases, bleeding and clotting disorders, cancer, and more.

Jieqing Zhu, PhD, is a Senior Investigator at Versiti Blood Research Institute and a Professor of Biochemistry at the Medical College of Wisconsin.

Read the full paper in Cell, the premier scientific journal in any area of experimental biology, including biochemistry, genetics and molecular biology. For more than 30 years, top international researchers have relied on Cell to publish high-impact papers that have come to form the foundation of contemporary life science research.