iCubed’s “Featured Researcher of the Month” for February could be called the “father” of the Institute for Immunology and Informatics. Dr. Leslie De Groot, who in addition to leading a successful career in immunology, has also contributed to the continuing success of another enterprise, iCubed, led by his daughter Dr. Annie De Groot.

Dr. De Groot trained at Columbia University College of Physicians and Surgeons and completed his residency at New York Presbyterian Hospital and Massachusetts General Hospital. He served in the Public Health Service at the National Institutes of Health and in Afghanistan and spent 12 years at Massachusetts General Hospital. He next moved on to the Massachusetts Institute of Technology before joining the Department of Medicine at the University of Chicago. While at UC, Dr. De Groot was the head of the Thyroid Study Unit as well as head of the Endocrine Section. He joined the Endocrine Division at Brown University in January 2005 and moved to the University of Rhode Island in 2009.

While at Brown, Dr. De Groot and Dr. Hidefumi Inaba conducted research which involved determining the dominant T cell epitopes in human TSH Receptor, the auto-antigen in Graves’ disease (GD), both in  a transgenic  mouse model, and in human subjects. They studied Regulatory T cells in GD and determined their numbers to be normal, in contrast to some prior reports suggesting they were low. They also studied the specific interaction between TSH receptor epitopes and the human HLA molecule DR301 and explained how and why certain epitopes are selected for involvement in the immune response. Lastly, Dr. De Groot and Dr. Inaba studied methods for expanding the numbers of regulatory cells, believing this might be one approach to treatment of auto-immunity as in GD.

After joining URI, Dr. De Groot, along with Assistant Research Professor Dr. Leonard Moise, proposed to improve outcomes for GD patients by developing a therapy that addresses the underpinnings of the immunological breakdown leading to GD. Their approach focuses on restoring immunological control to prevent the body from recognizing itself as foreign. To accomplish this goal, they applied a novel finding in their laboratory that provides insight into a natural mechanism that prevents autoimmunity. In a series of preliminary studies, they demonstrated that Tregitopes suppress inflammatory immune responses, like those that produce GD. Importantly, they noted this effect in the context of proteins specifically associated with the inflammatory response.

Dr. De Groot and Dr. Moise hope to carry forward these initial findings by applying them in the context of the GD-associated protein, thyroid stimulating hormone receptor. Tregitopes may suppress the inflammatory effects of cells from GD patients, thus providing support that a Tregitope-based therapy can be developed to treat GD.

Dr. De Groot has more than 400 publications and received the Endocrine Society award as “Distinguished Educator” in 2004. Perhaps his best known publication is the three volume textbook “Endocrinology” which he edited through six editions over the past 30 years. He is currently excited by the educational possibilities of the two web books he directs, www.endotext.org and www.thyroidmanager.org, which receive over 80,000 hits each day from 6000 visitors around the world.