A5013557958- Cancer Cells and Metastasis
- Microfluidic and Bio-sensing Technologies
- Cancer Genomics and Diagnostics
- Mass Spectrometry Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Liver Disease and Transplantation
- Organ Transplantation Techniques and Outcomes
- Microfluidic and Capillary Electrophoresis Applications
- Amyotrophic Lateral Sclerosis Research
- Advanced Proteomics Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Thermal Regulation in Medicine
- Pancreatic and Hepatic Oncology Research
- Mesenchymal stem cell research
- Cancer Immunotherapy and Biomarkers
- Neonatal Respiratory Health Research
- Organ Donation and Transplantation
- Phagocytosis and Immune Regulation
- Advanced Fluorescence Microscopy Techniques
- Neurological diseases and metabolism
- Genetic Neurodegenerative Diseases
- Zebrafish Biomedical Research Applications
- PI3K/AKT/mTOR signaling in cancer
Massachusetts General Hospital
2014-2025
Harvard University
2013-2025
Shriners Hospitals for Children - Boston
2018-2025
Shriners Hospitals for Children - Erie
2021
Keio University
2018
Boston University
2014
Brandeis University
2008-2011
A multistage microfluidic chip is capable of sorting rare EpCAM + and − CTCs from cancer patients’ whole blood.
Significance Isolation of sufficient numbers circulating tumor cells (CTCs) in cancer patients could provide an alternative to invasive biopsies, providing multianalyte cell-based biomarkers that are not available from current plasma DNA sequencing. Given the average prevalence at one CTC per billion blood cells, very large volumes must be screened enough CTCs for reliable clinical applications. By creating ultrahigh-throughput magnetic sorter, we demonstrate efficient removal leukocytes...
Circulating tumor cells (CTCs) are a treasure trove of information regarding the location, type and stage cancer being pursued as both diagnostic target means guiding personalized treatment. Most isolation technologies utilize properties CTCs themselves such surface antigens (e.g., epithelial cell adhesion molecule or EpCAM) size to separate them from blood populations. We present an automated monolithic chip with 128 multiplexed deterministic lateral displacement devices containing ~1.5...
Abstract Metastasis-competent circulating tumour cells (CTCs) experience oxidative stress in the bloodstream, but their survival mechanisms are not well defined. Here, comparing single-cell RNA-Seq profiles of CTCs from breast, prostate and lung cancers, we observe consistent induction β-globin ( HBB ), its partner α-globin HBA ). The tumour-specific origin is confirmed by sequence polymorphisms within human xenograft-derived mouse models. Increased intracellular reactive oxygen species...
Abstract Innovative microfluidic technology has enabled massively parallelized and extremely efficient biological clinical assays. Many applications developed executed with traditional bulk processing techniques have been translated streamlined through the notable exception of sample volume reduction or centrifugation, one most widely utilized processes in sciences. We utilize high-speed phenomenon known as inertial focusing combined hydraulic resistance controlled multiplexed...
Top-down and bottom-up mass spectrometry methods can generate gas phase fragments use these to identify proteins. methods, in addition, provide the of protein itself therefore additional structural information. Despite conceptual advantage top-down market share belongs as a result their more robust sample preparation, fragmentation, data processing methods. Here we report improved fragmentation for spectrometry. Specifically funnel-skimmer dissociation, variation nozzle-skimmer compare its...
At least 119 mutations in the gene encoding copper/zinc superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis by an unidentified toxic gain of function. We compared dynamic properties 13 as-isolated, partially metallated, SOD1 variant enzymes using hydrogen-deuterium exchange. identified a shared property these familial sclerosis-related variants, namely structural and change affecting electrostatic loop (loop VII) SOD1. Furthermore, variants that have severely compromised metal...
Active sites may be regarded as layers of residues, whereby the residues that interact directly with substrate also in a second shell and these turn third shell. These have distinct roles maintaining essential chemical properties first-shell catalytic particularly their spatial arrangement relative to binding pocket, electrostatic dynamic properties. The extent which remote participate catalysis precisely how they affect remains unexplored. To improve our understanding second- third-shell...
Abstract Circulating monocytes contribute to the defense against pathogens and play a crucial role in maintaining immune homeostasis. While there is substantial evidence regarding triggers of monocyte activation, our understanding how function restored toward homeostasis after activation remains limited. Here, we assessed changes anisocytosis upon blood, measured by distribution width (MDW), biomarker for sepsis. We determined that increase MDW post‐lipopolysaccharide (LPS) stimulation blood...
Abstract Introduction Burn injuries trigger pathological immune responses. However, our ability to monitor these evolving responses is constrained by the intricate confluence of cellular, biochemical, and metabolic alterations that occur concurrently post-injury. In this study, we concentrate on monocytes, which serve as key mediators burn-induced changes potential biomarkers for monitoring after injury. Methods We enrolled adult pediatric patients with major burn (>15%) collected...
Abstract Gradual rewarming from hypothermic to normothermic is a novel perfusion modality with superior outcome sudden normothermic. However, the identification of an oxygen carrier that could function at temperature range 4 7°C or whether it necessary use during kidney rewarming, remains unresolved. This study was designed test hemoglobin‐based (HBOC) gradual as alternative simple dissolved oxygen. In this study, 10 rat kidneys were randomly divided into control and HBOC group. group, no...
Single cell technologies have described heterogeneity across tissues, but the spatial distribution and forces that drive single phenotypes not been well defined. Combining RNA protein analytics in pancreatic cancer (PDAC) model systems, we demonstrated role of stromal fibroblasts shaping PDAC towards invasive (EMT) proliferative (PRO) phenotypes. Using highcontent digital imaging situ hybridization 195 tumors, observed these EMT PRO subpopulations 319,626 individual cells. Interestingly,...
Ex situ machine perfusion is a promising technology to help improve organ viability prior transplantation. However, preclinical studies using discarded human livers evaluate therapeutic interventions and optimize conditions are limited by significant graft heterogeneity. In order the efficacy reproducibility of future studies, split-liver model was developed allow simultaneous left right lobes, allowing one lobe serve as control for other. Eleven were surgically split, both lobes perfused...
Abstract The recovery of patients after severe burns is a long and complex process. Genomic analysis white blood cells from burn trauma revealed excessive prolonged innate immune activation in with complicated outcomes. However, translating this knowledge into practical biomarkers has not been possible yet. Although several for monitoring have proposed, their ability to accurately distinguish between inflammation stemming initial tissue destruction, infections, organ failure complications...
This article presents a memory efficient algorithm for accurately calculating the isotopic fine structures of molecules. Treating individual species molecule as different mass states, we introduce concept transitions between states and represent all in hierarchical structure. We show that there exists simple relationship two at levels allows us to efficiently compute both abundance every state small medium-sized molecule, whose gross include number structures. A truncated calculation this...
Abstract Introduction Severe burn injuries trigger pathological immune responses. However, our ability to monitor these evolving responses is constrained by the intricate confluence of cellular, biochemical, and metabolic alterations that occur concurrently post-injury. Here, we focus on monocytes as integrators changes triggered injury potential biomarkers for after injury. Methods We enrolled patients with major (15% or more) collected blood samples twice a week duration hospital stay....
Abstract Our previous work postulated a transition concept among different isotopic mass states (i.e., species) of molecule, and developed hierarchical algorithm for accurately calculating their masses abundances. A theoretical spectrum can be generated by convoluting peak shape function to these discrete states. This approach suffers from limited memory if level in the structure has too many Here we present efficient divide‐and‐recursively‐combine do calculation, which also improves...
The relationship of magnetic field strength and Fourier transform ion cyclotron resonance mass spectrometry performance was tested using three instruments with the same design but different fields 4.7, 7, 9.4 tesla. We found that theoretically predicted "transformative" effects are indeed observed experimentally. most striking were accuracy demonstrated approximately second to third order improvement field, depending upon charge state analyte, peak splitting, which prohibited automated data...
Background Donation after circulatory death (DCD) grafts are vital for increasing available donor organs. Gradual rewarming during machine perfusion has proven effective in mitigating reperfusion injury and enhancing graft quality. Limited data exist on artificial oxygen carriers as an solution to meet the metabolic demand with temperature changes. The aim of present study was assess efficacy safety utilizing a hemoglobin-based carrier (HBOC) gradual DCD rat livers. Methods Liver were...