In my lab, we are interested in human diseases caused by abnormal lymphocyte development or function. In the past, we have studied a form of severe combined immunodeficiency caused by a mutation in the gene adenosine deaminase (ADA). Children who inherit ADA gene mutations lack T and B lymphocytes and will die of an infection if they do not receive a bone marrow transplant. We developed a model to study this condition using cultured cells from the thymuses, where T cells develop, of children undergoing corrective cardiac surgery. These studies are important because abnormal development of T cells in the thymus can lead to leukemia or lymphoma.

Another area of interest for us is a second enzyme called ecto-5′-nucleotidase or 5′-NT. This enzyme produces adenosine, a substance that can bind to cell surface adenosine receptors found on almost all cells. Adenosine receptors regulate a variety of important physiological processes, such as nerve transmission, heart rate, kidney function, smooth muscle contraction, and inflammation. My colleagues and I have engineered a strain of mice that lacks 5′-NT and are using these mice to understand the function of this enzyme. Work in my lab centers on the ability of adenosine produced by 5′-NT to modulate various types of inflammatory responses. We have also discovered that 5’-NT contributes to the immunosuppressive environment surrounding many tumors. Inhibiting 5′-NT may be a new strategy for treating some types of cancers. We have shared our mice with many other groups of scientists all over the United States and even in Europe, Japan, China, and Australia so that investigators with expertise in a wide variety of fields can have access to this unique tool.

A third area of interest in my lab is autoimmunity. In the past, we studied the immune response of patients with lupus to immunization with the influenza vaccine. We were happy to find that most lupus patients did not experience a flare in their disease after vaccination. Together with other scientists at OMRF, we are now studying Sjögren’s disease, an autoimmune disease that causes severe dry eyes and dry mouth.