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Bio
Engineers now have the tools to design biological products and processes at the molecular level. Proteins are of particular therapeutic interest, because proteins mediate most biochemical processes both inside and outside cells. The ability to manipulate the strength and specificity of protein binding events provides tremendous leverage for the development of novel biopharmaceuticals. The Wittrup laboratory is developing powerful new tools for protein engineering, and applying them both to particular disease targets and to bettering our understanding of protein structure/function relationships. In the absence of predictive capabilities for protein design, a directed evolution or combinatorial library screening strategy can be effectively applied to alter protein properties in a desired fashion. The group is applying quantitative engineering analyses of the relevant kinetic and statistical processes to develop optimal search strategies on the protein fitness landscape. In particular, the lab has developed a method for protein display on the surface of yeast cells that, for example, enabled engineering of a noncovalent protein-ligand bond with a dissociation half-time over one week. The group is engineering potential protein biopharmaceuticals in areas where molecular understanding of disease pathology is sufficient to hypothesize particular objective functions to target. For example, antibodies can be used to target cell-killing modalities to cancerous cells, given sufficiently strong and specific binding properties. Growth factors that carry signals between cells do so via particular binding events that, if manipulated to alter intracellular trafficking or signalling outcomes, could alter immune responses in precisely defined ways. Finally, viral and nonviral vectors for gene therapy could be targeted to specific cells and tissues via alteration of an exchangeable antibody recognition module. Altered proteins developed in this work can also provide a potential vehicle for new insights into the mechanisms of protein-ligand binding. The lab is performing biophysical analyses of the kinetic, thermodynamic, and structural aspects of engineered protein function in order to contribute to an improved understanding of protein binding processes.
Research Interests
Papers共 403 篇Author StatisticsCo-AuthorSimilar Experts
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Jordan A Stinson, Matheus Moreno P Barbosa,Allison Sheen,Noor Momin,Elizabeth Fink,Jordan Hampel,Kim A Selting,Rebecca L Kamerer,Keith L Bailey,K Dane Wittrup,Timothy M Fan
Clinical cancer research : an official journal of the American Association for Cancer Research (2024)
Leyuan Ma, Ranjani Ramasubramanian,Naveen Mehta,Benjamin Cossette,Duncan Morgan, Ina Sukaj,Elisa Bergaggio,Stephan Kadauke,Regina Myers,Luca Paruzzo,Guido Ghilardi, Tomasz Grzywa,
bioRxiv : the preprint server for biology (2024)
Jordan A Stinson, Matheus Moreno P Barbosa,Allison Sheen,Noor Momin,Elizabeth Fink,Jordan Hampel,Kimberly Selting,Rebecca Kamerer,Keith L Bailey,K Dane Wittrup,Timothy M Fan
bioRxiv : the preprint server for biology (2024)
ACS synthetic biologyno. 1 (2024): 220-229
Luciano Santollani,Laura Maiorino,Yiming J Zhang,Joseph R Palmeri,Jordan A Stinson,Lauren R Duhamel,Kashif Qureshi, Jack R Suggs, Owen T Porth,William Pinney, Riyam Al Msari, Agnes A Walsh,
Nature immunologypp.1-10, (2024)
Nature Communicationsno. 1 (2024): 1-19
Francesca Alvarez Calderon,Byong H Kang,Oleksandr Kyrysyuk,Shiwei Zheng, Hao Wang,Nathan D Mathewson,Adrienne M Luoma, Xiaohan Ning,Jason Pyrdol, Xuan Cao,Mario L Suvà,Guo-Cheng Yuan,
Bloodno. 12 (2024): 1124-1138
Luciano Santollani,Yiming J Zhang,Laura Maiorino,Joseph R Palmeri,Jordan A Stinson,Lauren R Duhamel,Kashif Qureshi, Jack R Suggs, Owen T Porth,William Pinney, Riyam Al Msari,K Dane Wittrup,
bioRxiv : the preprint server for biology (2024)
Naveen K. Mehta,Kavya Rakhra,Kristan A. Meetze, Bochong Li,Noor Momin, Jason Y.H. Chang,K. Dane Wittrup,Patrick A. Baeuerle,Jennifer S. Michaelson
crossref(2024)
Journal for ImmunoTherapy of Cancerno. Suppl 1 (2023)
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#Papers: 389
#Citation: 22250
H-Index: 76
G-Index: 142
Sociability: 7
Diversity: 3
Activity: 112
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