Abraham (Avi) Kupfer, Ph.D.
Department of Cell Biology
Johns Hopkins University School of Medicine
733 N. Broadway, 623 MRB (Lab: 632 MRB)
Baltimore, MD 21205
Academic TitlesProfessor Emeritus
Research TopicCellular interactions in the immune system; the immunological synapse; mechanisms of T cell activation and induction of tolerance.
Research Topic: Signaling, cell-cell interaction, intercellular communication, immune cell activation, multi-dimensional imaging, novel biosensors
The long-term goal of our studies is to understand the complex cellular and molecular mechanisms of inter- and intra-cellular communication in the immune system. T cells play a central role in regulating the cellular and humoral responses towards invading pathogens and malignant transformation. On the flip side, improper recognition of self-antigens by T cells is the primary cause of most autoimmune diseases. The critical molecular and cellular mechanisms that the T cells use to sense their environment and how this sensing is relayed into a particular functional response are still unclear.
Using a combination of molecular biology, biochemical and novel multi-dimensional digital imaging approaches we study in real-time complex multi dimensional signal integration during the interaction of T cells with live antigen-presenting cells. These studies led to the discovery of the Immunological-Synapse. This synapse is composed of different Supra-Molecular Activation Clusters (SMACs) of receptors, cytoskeletal and signaling proteins. We continue to study the 4-dimensional structure and function of the dynamic SMACs and their roles in regulation of the immune response. We identified Protein Kinase C-theta as the first key protein that serves as master switch for determining the physiological outcome to initial T cell activation. Using retroviral infection of T cells we designed a new biosensor for the c-SMAC of the Synapse. We are using now a genetic yeast two-hybrid screen with this biosensor to identify new proteins that are important for the structure and function of the Immunological Synapse.