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Tuning cytokine receptor signaling with natural and engineered ligands

Wednesday, November 5, 2014


K. Christopher Garcia, Ph.D.
HHMI-Stanford University School of Medicine

Dr. Garcia studies the structure and function of cell-surface receptor recognition and activation in biological systems directly implicated in human health and disease. These receptor systems are at the interface of immunity, neurobiology, and microbial pathogenesis. He focuses on “shared” receptors, which can recognize and bind to several different molecules, or ligands, often eliciting unique responses. Uniting structural studies of these receptors with biochemical and biophysical experiments, Garcia has identified new paradigms for recognition and activation of a variety of receptors that play critical roles in autoimmunity, cancer, neural growth and repair, and blood-pressure regulation.Garcia’s long-term goal is to probe these systems more deeply. Understanding the many ways in which the relatively simple act of ligand binding prompts conformational change and ultimately activates receptors should help researchers design drugs targeting receptors whose functions affect human disease.


Dr. Garcia’s laboratory investigates the structural and functional aspects of cell-surface receptor recognition and activation in receptor-ligand systems with relevance to human health and disease. Structural information is exploited to understand the mechanisms of ligand recognition and signaling, as well as to inform engineering efforts to manipulate receptor signaling and generate therapeutics. The receptor systems studied derive principally from the immune system (TCR/MHC, cytokines), but additionally encompass several systems that are also important in neurobiology (Semaphorins) and development (Wnt, Notch). A major focus of the lab is on “shared” pleiotropic receptors, to understand the biophysical basis by which different cross-reactive ligands and receptors can elicit unique intracellular responses and functional outcomes. A recent effort in the lab has been to “deorphanize” cell surface receptors, the vast majority of which remain un-paired with a known ligand. In Dr. Garcia’s seminar, he will discuss two new projects that focus on systems that exhibit properties of receptor-ligand pleiotropy: 1) Deconvoluting the cross-reactivity of Wnt interactions with Frizzled receptors, and 2) Identification of a new family of Immunoglobulin receptors and ligands that mediate cell-cell adhesion in neuronal structures.

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