Download CBE Seminar - Chemical Engineering, University of Delaware

CBE Seminar
Dr. Jamie B. Spangler
Postdoctoral Fellow
Stanford University School of Medicine
DATE:
January 19, 2017
TIME:
10:00 am
Dr. Jamie Spangler obtained a Bachelor of Science
LOCATION:
Degree in Biomedical Engineering at Johns Hopkins
366 CLB
University and went on to conduct her Ph.D. research
in Biological Engineering in Professor K. Dane Wittrup’s
group at MIT, studying antibody-mediated down-regulation of
epidermal growth factor receptor as a new mechanism for cancer
therapy. She is currently a postdoctoral fellow in Professor K. Christopher
Garcia’s lab in the Molecular & Cellular Physiology and Structural Biology
departments at Stanford University School of Medicine. Her work focuses on engineering
cytokine systems to therapeutically bias immune homeostasis. Dr. Spangler has been
awarded a National Defense Science and Engineering Graduate Fellowship, a Repligen
Koch Institute for Integrative Cancer Research Fellowship, and most recently a Leukemia &
Lymphoma Society postdoctoral fellowship for her research.
Reshaping the Immune Response through Molecular
Engineering
Cytokines constitute a large class of secreted proteins that signal through membraneembedded receptors to orchestrate all aspects of the immune response. Their critical
role in immune regulation has motivated the therapeutic use of cytokines to treat a
range of diseases including autoimmune disorders, infectious diseases, and cancer.
However, clinical performance has been limited by such challenges as pleiotropy,
redundancy, and poor pharmacokinetic properties, which confound efficacy and
lead to harmful off-target effects. Recent advances in protein engineering present
exciting opportunities to apply molecular design tools to overcome the limitations of
naturally occurring cytokines. I will describe two molecular engineering approaches I
have pursued toward selectively tuning the immune response to achieve targeted
disease therapy: (1) I elucidated the structural mechanisms through which cytokinetargeted antibodies bias immune homeostasis and leveraged crystallographic insights
to design enhanced cytokine-directed therapeutic antibodies; and (2) I engineered
a novel class of antibody-based agonists that functionally recapitulate cytokine
activity by using a single binding site to bridge the interface between two receptors in
a heterodimeric signaling complex. Collectively, these efforts offer new insight into the
determinants of protein function and construct a molecular blueprint for
therapeutically biasing immune activity.
Department of Chemical & Biomolecular Engineering