Dane K Wittrup

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Understanding allostery may serve to both elucidate mechanisms of protein regulation and provide a basis for engineering active mutants. Herein we describe directed evolution applied to the integrin alpha(L) inserted domain for studying allostery by using a yeast surface display system. Many hot spots for activation are identified, and some single mutants(More)
Bovine pancreatic trypsin inhibitor (BPTI) was expressed and secreted from a synthetic gene as a model system for the study of protein folding and secretion in Saccharomyces cerevisiae. The efficiency of different leader sequences in directing BPTI secretion was examined, and up to 11 micrograms/ml of active BPTI was secreted. In some fusion constructs,(More)
The goals of our research are to develop high-affinity and high-stability antibodies and fragments thereof for targeting tumor-specific antigens in an attempt to develop new therapeutic agents for human hepatocellular carcinoma (HCC). Tumor-associated antigens are excellent targets for drug and gene delivery, and offer the advantage of high cellular(More)
Epidermal Growth Factor Receptor (EGFR) is involved in stimulating the growth of many human tumors, but the success of therapeutic agents has been limited in part by interference from the EGFR on normal tissues. Previously, we reported an antibody (mab806) against a truncated form of EGFR found commonly in gliomas. Remarkably, it also recognizes full-length(More)
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Small-molecule ligands specific for tumor-associated surface receptors have wide applications in cancer diagnosis and therapy. Achieving high-affinity binding to the desired target is important for improving detection limits and for increasing therapeutic efficacy. However, the affinity required for maximal binding and retention remains unknown. Here, we(More)
Early enthusiasm over angiogenic therapy, a method to induce vascular regeneration to treat ischemic tissue with growth factors, has been tempered by a series of unsuccessful clinical trials with limited late efficacy and a wide range of mixed results. This thesis was designed to examine critically whether the lack of late efficacy of local delivery of(More)