NIH Awards $3.6M Toward Development of Disease-Fighting Biotherapeutics

A UMD professor of cell biology and molecular genetics and a fellow at the Institute for Bioscience and Biotechnology Research (IBBR), is one of a team of investigators that received a $3.6 million National Institutes of Health award to expand the scope of its research on T cells, an important component of human immune response.

Roy Mariuzza will work with Dr. Dario Vignali, vice chair of immunology at the University of Pittsburgh, to further characterize LAG3—a well-known inhibitory receptor on T cells. LAG3 activity has been implicated in various cancers, as well as in the chronic infections associated with malaria and HIV.

The human immune system fights infectious agents and protects us from cancer, but also requires many mechanisms of self-regulation to minimize damage to our own tissues from autoimmune diseases and excessive inflammation. An important part of the checks and balances of the immune system involves “immune checkpoint molecules,” receptors that turn down the immune response.

Pathogens and tumor cells thrive, in part, by engaging these immune checkpoint molecules, making them important drug targets in the fight against infectious disease and cancer. However, “the immune system is famously complicated and intricate,” said Mariuzza, “so blocking a single checkpoint is unlikely to be effective for all applications.”

Mariuzza’s group will determine the 3D structure of LAG3 bound to various molecules. This will provide structural insight into its function to support the development of new biotherapeutics now being pursued by numerous companies.

IBBR is a joint research enterprise of the University of Maryland, College Park, the University of Maryland Baltimore, and the National Institute of Standards and Technology.