A5084971834- Click Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Chemical Synthesis and Analysis
- Single-cell and spatial transcriptomics
- Monoclonal and Polyclonal Antibodies Research
- Neurological disorders and treatments
- Extracellular vesicles in disease
- American Environmental and Regional History
- Advanced Biosensing Techniques and Applications
- EEG and Brain-Computer Interfaces
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Musculoskeletal pain and rehabilitation
- Cancer Cells and Metastasis
- Inflammatory Biomarkers in Disease Prognosis
- Transboundary Water Resource Management
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- HIV Research and Treatment
- Nanoplatforms for cancer theranostics
- Immune Cell Function and Interaction
- Advanced Fluorescence Microscopy Techniques
- COVID-19 Clinical Research Studies
- Neuroscience and Neural Engineering
- Parkinson's Disease Mechanisms and Treatments
Harvard University
1998-2025
Massachusetts General Hospital
2016-2025
Center for Systems Biology
2016-2025
Wienerberger (Czechia)
2022
TU Wien
2022
Medical University of Vienna
2022
Microsoft (United States)
2014
University of Minnesota
2003-2012
University of Washington
2007-2008
Los Alamos National Laboratory
2007
Tumor-associated macrophages limit anti–PD-1 effects by removing the antibody from CD8 + T cells.
The fastest and the brightest: A new design that intimately connects tetrazine to a BODIPY fluorophore enables exceptionally efficient energy transfer quenching. Upon reaction of tetrazine, brightness increases more than thousand-fold, which is fluorogenic activation up two orders magnitude greater previously described. As service our authors readers, this journal provides supporting information supplied by authors. Such materials are peer reviewed may be re-organized for online delivery,...
<h3>Importance</h3> Coronavirus disease 2019 (COVID-19) is an acute respiratory illness with a high rate of hospitalization and mortality. Biomarkers are urgently needed for patient risk stratification. Red blood cell distribution width (RDW), component complete counts that reflects cellular volume variation, has been shown to be associated elevated morbidity mortality in wide range diseases. <h3>Objective</h3> To investigate whether association between RDW at hospital admission during...
Abstract We have developed a series of new ultrafluorogenic probes in the blue‐green region visible‐light spectrum that display fluorescence enhancement exceeding 11 000‐fold. These fluorogenic dyes integrate coumarin fluorochrome with bioorthogonal trans ‐cyclooctene(TCO)–tetrazine chemistry platform. By exploiting highly efficient through‐bond energy transfer (TBET), these exhibit highest brightness enhancements reported for any dyes. No‐wash, imaging diverse targets including cell‐surface...
Recent developments in bond cleavage reactions have expanded the scope of bioorthogonal chemistry beyond click ligation and enabled new strategies for probe activation therapeutic delivery. These applications, however, remain their infancy, with further innovations needed to achieve efficiency required versatile broadly useful tools vivo. Among these chemistries, tetrazine/ trans-cyclooctene click-to-release reaction has exemplary kinetics adaptability but achieves only partial release is...
Exosomes and extracellular vesicles (EV) are increasingly being explored as circulating biomarkers, but their heterogenous composition will likely mandate the development of multiplexed EV technologies. Iteratively analyses near single EVs have been challenging to implement beyond a few colors during spectral sensing. Here we developed analysis technique (MASEV) interrogate thousands individual 5 cycles multi-channel fluorescence staining for 15 biomarkers. Contrary common belief, show that:...
The exploitation of biological macromolecules, such as nucleic acids, for the fabrication advanced materials is a promising area research. Although greater variety structural and functional uses can be envisioned protein-based materials, systematic approaches their construction have yet to emerge. Consistent with theoretical models polymer macrocyclization, we demonstrated that, in presence dimeric methotrexate (bisMTX), wild-type Escherichia coli dihydrofolate reductase (DHFR) molecules...
There is a need for novel analytical techniques to study the composition of single extracellular vesicles (EV). Such are required improve understanding heterogeneous EV populations, allow identification unique subpopulations, and enable earlier more sensitive disease detection. Because small size their low protein content, ultrahigh sensitivity technologies required. Here, an immuno-droplet digital polymerase chain reaction (iddPCR) amplification method described that allows multiplexed...
Tumor cell-derived extracellular vesicles (EVs) are being explored as circulating biomarkers, but it is unclear whether bulk measurements will allow early cancer detection. We hypothesized that a single-EV analysis (sEVA) technique could potentially improve diagnostic accuracy. Using pancreatic (PDAC), we analyzed the composition of putative markers in 11 model lines. In parental PDAC cells positive for KRASmut and/or P53mut proteins, only ~40% EVs were also positive. blinded study involving...
Inflammation is the physiologic reaction to cellular and tissue damage caused by trauma, ischemia, infection, other pathologic conditions. Elevation of white blood cell count (WBC) altered levels acute phase reactants are cardinal signs inflammation, but dynamics these changes their resolution not well established. Here we studied inflammatory recovery from infection tracking longitudinal clinical laboratory measurements in hospitalized patients. We identified a universal trajectory defined...
Complete blood count indices and their ratios are associated with adverse clinical outcomes for many acute illnesses, but the mechanisms generating these associations not fully understood. Recent identification of a consistent pattern white cell platelet co-regulation during inflammatory recovery provides potentially unifying explanation. Here we show that platelet-to-white-cell ratio, which was selected based on this conserved pattern, is more strongly mortality than other markers in four...
Am schnellsten und hellsten: Die enge Verknüpfung von Tetrazin an ein BODIPY-Fluorophor führt zu einem außergewöhnlich effizienten Energietransfer starker Fluoreszenzlöschung. Nach Reaktion des Tetrazins nimmt die Fluoreszenzintensität um mehr als das Tausendfache zu. Damit ist fluorogene Aktivierung zwei Größenordnungen höher zuvor beschrieben. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed may...
Abstract We have developed a series of new ultrafluorogenic probes in the blue‐green region visible‐light spectrum that display fluorescence enhancement exceeding 11 000‐fold. These fluorogenic dyes integrate coumarin fluorochrome with bioorthogonal trans ‐cyclooctene(TCO)–tetrazine chemistry platform. By exploiting highly efficient through‐bond energy transfer (TBET), these exhibit highest brightness enhancements reported for any dyes. No‐wash, imaging diverse targets including cell‐surface...
Herein we describe the development and application of a bioorthogonal fluorogenic chelate linker that can be used for facile creation labeled imaging agents. The is based on trans-cyclooctene(TCO)-tetrazine(Tz) chemistry platform incorporates deferoxamine (DFO) as (89)Zr PET tracer BODIPY fluorophore multimodal imaging. rapid (<3 min) ligation between mAb-TCO Tz-BODIPY-DFO chelator monitored using fluorescence allows determination labeling completion. Utilizing mAb DFO facilitates in...
Serial tissue sampling has become essential in guiding modern targeted and personalized cancer treatments. An alternative to image guided core biopsies are fine needle aspirates (FNA) that yield cells rather than tissues but much better tolerated have lower complication rates. The efficient pathway analysis of such the clinic been difficult, time consuming costly. Here we develop an antibody-DNA barcoding approach where harvested can be rapidly re-stained through use custom designed...
Bioorthogonal chemistry is bridging the divide between static chemical connectivity and dynamic physiologic regulation of molecular state, enabling in situ transformations that drive multiple technologies. In spite maturing mechanistic understanding new bioorthogonal bond-cleavage reactions, broader goal ON/OFF control has been limited by inability existing systems to achieve both fast (i.e., seconds minutes, not hours) complete >99%) cleavage. To attain stringent performance characteristics...
Rapid analysis of single and scant cell populations is essential in modern diagnostics, yet existing methods are often limited slow. Herein, we describe an ultra-fast, highly efficient cycling method for the cells based on unique linkers tetrazine (Tz)/trans-cyclooctene (TCO)-mediated quenching. Surprisingly, quenching reaction rates were more than 3 orders magnitude faster (t1/2 <1 s) predicted. This allowed multi-cycle staining immune profiling within hour, leveraging accelerated kinetics...
Abstract The ability to observe cells in live organisms is essential for understanding their function complex vivo milieus. A major challenge today has been the limited perform higher multiplexing beyond four six colors define cell subtypes vivo. Here, a click chemistry‐based strategy presented multiplexed imaging mouse models. method uses scission‐accelerated fluorophore exchange (SAFE), which exploits highly efficient bioorthogonal mechanism completely remove fluorescent signal from...
Abstract Organoids are becoming increasingly relevant in biology and medicine for their physiological complexity accuracy modeling human disease. To fully assess biological profile while preserving spatial information, spatiotemporal imaging tools warranted. While previously developed techniques, such as four‐dimensional (4D) live light‐sheet have yielded important clinical insights, these technologies lack the combination of cyclic multiplexed analysis. address challenges, bioorthogonal...
Bioorthogonal bond-cleavage reactions are powerful tools for investigating biological dynamics and advancing therapeutic strategies. Primed by click reactivity, the multi-step cascades that lead to bioorthogonal release have nevertheless been challenging navigate. For widely recognized tetrazine-triggered cleavage of trans-cyclooctenes (TCO), complexities post-click tautomerization key barrier achieving next-level molecular tools. Strategies anchor directing functionalities tetrazines (Tz)...
The management of brainstem metastases is challenging. Surgical treatment usually not an option, and chemotherapy limited utility. Stereotactic radiosurgery has emerged as a promising palliative modality in these cases. goal this study to assess our single institution experience treating with Gamma Knife (GKRS). This retrospective chart review studied 41 patients treated GKRS. most common primary tumors were lung, breast, renal cell carcinoma, melanoma. Median age at initial was 59 years....