Ann Marie Pendergast
Anthony R. Means Cancer Biology Professor

The goal of our research is to elucidate the role of tyrosine kinases of the Abl family in the regulation of normal development and pathological conditions such as cancer, bacterial pathogenesis, muscular dystrophies, neurodegenerative disorders, and immune deficiencies. Through the study of Abl tyrosine kinases and associated adaptors, we have gained novel insights on the regulation of cell proliferation, survival, cell morphology, migration, and synapse formation. We have shown that the endogenous Abl kinases are activated by growth factor receptors and function to link these receptors to reorganization of the actin cytoskeleton. Abl kinases are also activated by the Muscle Specific Tyrosine Kinase (MuSK) on the postsynaptic side of the neuromuscular junction (NMJ) in response to the nerve-derived organizing factor agrin. Activation of the endogenous Abl family kinases in muscle is required for the clustering of Acetylcholine receptors (AChRs), which is essential for muscle function. These results reveal a novel role for Abl family kinases in synapse formation and suggest that Abl kinases may modulate synapse formation and/or maintenance in the central nervous system. We are currently employing mouse models to define the role of Abl kinases and their targets in cellular processes ranging from synapse formation to learning and memory.

More recently, we have begun to define the machinery that regulates actin polymerization at sites of cell-cell contact, including the T cell:B cell interface. We have identified the Abi (Abl interactor)proteins as critical components of an Abi/Wave protein complex that regulates actin polymerization at the immunological synapse of activated T cells. The Abi/Wave complex links T cell receptor stimulation to Rac-dependent actin polymerization. We have used cell-based assays and knockout mice to define the role for Abi proteins in T cell signaling and proliferation. Our work lays the ground for an understanding of the mechanisms that control actin dynamics at sites of cell-cell contact.

Current Appointments & Affiliations

Contact Information

  • C233A Lev Sci Res Ctr, Durham, NC 27708
  • Duke Box 3813, Durham, NC 27710

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