Larry R. Pease, Ph.D.

How the immune system recognizes threats is fundamental to the maintenance of health. Dr. Pease's laboratory has been investigating the interactions between T lymphocytes and antigen presenting cells with the goal of understanding the regulatory events governing communication between these central immune players; discerning how the body distinguishes self from non self; and applying this emerging body of knowledge to control immunity by focusing the immune response on threats such as infection and cancer.

Ongoing studies also seek to direct immunity in the healing process, and to prevent the body from attacking one's own organs as occurs in autoimmune diseases such as type 1 diabetes. Molecular signatures of immune status and immune potential might be applied as biomarkers of disease prognosis and expected outocomes following therapeutic intervention. Dr. Pease's group is using RNA expression profiles to define relevant immune profiles of healthy and patient populations to address this hypothesis.

Focus areas

• Investigating the impact of MHC class I structural diversity on the conserved T cell receptor: MHC contact sites along the molecular interface between ligand and receptor
• Elucidating the molecular events responsible for differential regulation of classical MHC class I genes during virus infection in the CNS
• Evaluating the relationship between strength of signal through the T cell receptor and T cell function in models of cancer immunity and type 1 diabetes
• Understanding how the immune system can direct repair of injured tissues in the central nervous system caused by multiple sclerosis and promote the transdifferentiation of liver cells in to sites of insulin production during acute diabetes
• Describing molecular signatures of immune status and immune response potential using RNA expression signatures in people as biomarkers for disease progression and response to therapy

Significance to patient care

Inflammation is a key component of many different diseases. Understanding how to reduce inflammation (autoimmunity or chronic inflammation) or enhance immunity (antiviral or cancer immunotherapy) can be key to storing health. We are studying new ways of activating immunity and inherent mechanisms to control inflammation that are applicable to diseases including breast cancer, lymphoma, melanoma, virus infection, and autoimmune syndromes including type 1 diabetes and multiple sclerosis.

In addition, we are seeking to develop a widely applicable approach to describing the immune status and immune potential of patients, with the goal of using this information to predict the course of disease and the response to available therapies. The ability to foresee these outcomes would inform treatment choices, increasing effectiveness and reducing the cost of care.