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Hidde L. Ploegh
Massachusetts Institute of Technology
658Publications
115H-index
49.3kCitations
Publications 658
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Protein ligases of defined substrate specificity are versatile tools for protein engineering. Upon completion of the reaction, the products of currently reported protein ligases contain the amino acid sequence that is recognized by that same ligase, resulting in repeated cycles of ligation and hydrolysis as competing reactions. Thus, previous efforts to sequentially label proteins at distinct positions required ligases of orthogonal specificity. A recombinant Oldenlandia affinis asparaginyl endo...
#1Jingjing Ling (MIT: Massachusetts Institute of Technology)H-Index: 4
#2Ross W Cheloha (Boston Children's Hospital)
Last.Hidde L. Ploegh (Boston Children's Hospital)H-Index: 7
view all 6 authors...
Abstract A substantial fraction of eukaryotic proteins is folded and modified in the endoplasmic reticulum (ER) prior to export and secretion. Proteins that enter the ER but fail to fold correctly must be degraded, mostly in a process termed ER-associated degradation (ERAD). Both protein folding in the ER and ERAD are essential for proper immune function. Several E2 and E3 enzymes localize to the ER and are essential for various aspects of ERAD, but their functions and regulation are incompletel...
#1Mohammad Rashidian (Harvard University)H-Index: 12
#2Martin W. LaFleur (Harvard University)H-Index: 6
Last.Cloud P. Paweletz (Harvard University)H-Index: 26
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Immunotherapy using checkpoint-blocking antibodies against PD-1 has produced impressive results in a wide range of cancers. However, the response remains heterogeneous among patients. We used noninvasive immuno-positron emission tomography (PET), using 89Zr-labeled PEGylated single-domain antibody fragments (nanobodies or VHHs), to explore the dynamics and distribution of intratumoral CD8+ T cells and CD11b+ myeloid cells in response to anti–PD-1 treatment in the MC38 colorectal mouse adenocarci...
#1Ross W Cheloha (Boston Children's Hospital)
#2Zeyang Li (MIT: Massachusetts Institute of Technology)H-Index: 8
Last.Hidde L. Ploegh (Boston Children's Hospital)H-Index: 7
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Commonly used methods to monitor internalization of cell surface structures involve application of fluorescently or otherwise labeled antibodies against the target of interest. Genetic modification of the protein of interest, for example through creation of fusions with fluorescent or enzymatically active protein domains, is another approach to follow trafficking behavior. The former approach requires indirect methods, such as multiple rounds of cell staining, to distinguish between a target tha...
#1Nida S. KhanH-Index: 6
#2Daniel P. Lukason (Harvard University)H-Index: 1
Last.Paige Negoro (Harvard University)H-Index: 2
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The tetraspanin CD82 is a potent suppressor of tumor metastasis and regulates several processes including signal transduction, cell adhesion, motility, and aggregation. However, the mechanisms by w...
#1Noor Jailkhani (MIT: Massachusetts Institute of Technology)H-Index: 2
#2Jessica R. Ingram (Harvard University)H-Index: 17
Last.Richard O. Hynes (MIT: Massachusetts Institute of Technology)H-Index: 123
view all 9 authors...
Extracellular matrix (ECM) deposition is a hallmark of many diseases, including cancer and fibroses. To exploit the ECM as an imaging and therapeutic target, we developed alpaca-derived libraries of “nanobodies” against disease-associated ECM proteins. We describe here one such nanobody, NJB2, specific for an alternatively spliced domain of fibronectin expressed in disease ECM and neovasculature. We showed by noninvasive in vivo immuno-PET/CT imaging that NJB2 detects primary tumors and metastat...
#1Tao Fang (Boston Children's Hospital)H-Index: 9
#2Ran LiH-Index: 5
Last.Hidde L. Ploegh (Boston Children's Hospital)H-Index: 7
view all 7 authors...
#1Yushu Joy Xie (MIT: Massachusetts Institute of Technology)H-Index: 1
#2Michael Dougan (Harvard University)H-Index: 15
Last.Richard O. Hynes (MIT: Massachusetts Institute of Technology)H-Index: 123
view all 11 authors...
Chimeric antigen receptor (CAR) T cell therapy has been successful in clinical trials against hematological cancers, but has experienced challenges in the treatment of solid tumors. One of the main difficulties lies in a paucity of tumor-specific targets that can serve as CAR recognition domains. We therefore focused on developing VHH-based, single-domain antibody (nanobody) CAR T cells that target aspects of the tumor microenvironment conserved across multiple cancer types. Many solid tumors ev...
#1Lina Bartels (UvA: University of Amsterdam)H-Index: 1
#2Hidde L. Ploegh (Boston Children's Hospital)H-Index: 7
Last.Koen WagnerH-Index: 8
view all 4 authors...
Abstract Historically, bispecific antibodies have been constructed through the genetic fusion of additional binding domains to the constant domains of the antibody heavy- or light chains. We present an alternative method for the introduction of additional functional domains to an antibody: site-specific chemo-enzymatic conjugation. This method relies on the combination of site-specific transpeptidases and bioorthogonal chemistry. Transpeptidases are used to site-specifically introduce chemical h...
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