The long-term goal of the TR&D 3 project is to develop high-impact, renewable, and open-source antibody reagents for cellular signaling and biomedical research. Specifically, we plan to focus on signaling events marked by important protein post-translational modifications (PTMs) such as phosphorylation and proteolytic zymogen activation events and their attendant protein conformational changes. While some antibodies do exist for specific phosphorylation sites, these antibodies are often unreliable, rarely renewable, and only available to a fraction of the modified sites. In addition, detecting functional forms of specific proteases has not been routinely possible in cells or in vivo due to the lack of conformationally selective antibodies. Furthermore, the industrialization of high-throughput recombinant antibody (rAb) selection and preparation has been thwarted by the absence of reliable robotic expression platforms. Thus, our immediate goals are to generate high-quality, open-source antibody reagents, by using novel phage display technologies and libraries developed by the UCSF Antibiome Center, to PTMs including: (i) phosphorylation sites, (ii) proteolytic neo-epitopes, and their attendant conformational changes, and (iii) alternative rapid antigen expression technologies such as in vitro transcription and translation (IVTT) that support all three TR&D projects. These goals compliment TR&Ds 1 and 2 by focusing on PTMs within key transmembrane proteins
Cormier, Anthony; Campbell, Melody G; Ito, Saburo et al. (2018) Cryo-EM structure of the ?v?8 integrin reveals a mechanism for stabilizing integrin extension. Nat Struct Mol Biol 25:698-704 |
Debela, Mekdes; Magdolen, Viktor; Skala, Wolfgang et al. (2018) Structural determinants of specificity and regulation of activity in the allosteric loop network of human KLK8/neuropsin. Sci Rep 8:10705 |
Takasaka, Naoki; Seed, Robert I; Cormier, Anthony et al. (2018) Integrin ?v?8-expressing tumor cells evade host immunity by regulating TGF-? activation in immune cells. JCI Insight 3: |
Li, Xiuyuan; Sevillano, Natalia; La Greca, Florencia et al. (2018) Structure-Function Analysis of the Extended Conformation of a Polyketide Synthase Module. J Am Chem Soc 140:6518-6521 |
Pollock, Samuel B; Hu, Amy; Mou, Yun et al. (2018) Highly multiplexed and quantitative cell-surface protein profiling using genetically barcoded antibodies. Proc Natl Acad Sci U S A 115:2836-2841 |
Truillet, Charles; Oh, Hsueh Ling J; Yeo, Siok Ping et al. (2018) Imaging PD-L1 Expression with ImmunoPET. Bioconjug Chem 29:96-103 |
Zhou, Yu; Zou, Hao; Yau, Christina et al. (2018) Discovery of internalizing antibodies to basal breast cancer cells. Protein Eng Des Sel 31:17-28 |
Isaac, R Stefan; Sanulli, Serena; Tibble, Ryan et al. (2017) Biochemical Basis for Distinct Roles of the Heterochromatin Proteins Swi6 and Chp2. J Mol Biol 429:3666-3677 |
Ivry, Sam L; Sharib, Jeremy M; Dominguez, Dana A et al. (2017) Global Protease Activity Profiling Provides Differential Diagnosis of Pancreatic Cysts. Clin Cancer Res 23:4865-4874 |
Dang, Shangyu; Feng, Shengjie; Tien, Jason et al. (2017) Cryo-EM structures of the TMEM16A calcium-activated chloride channel. Nature 552:426-429 |
Showing the most recent 10 out of 25 publications