A5052097356- Advanced biosensing and bioanalysis techniques
- T-cell and B-cell Immunology
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Liver physiology and pathology
- RNA Interference and Gene Delivery
- Biosensors and Analytical Detection
- Tissue Engineering and Regenerative Medicine
- Pancreatic function and diabetes
- Immune Response and Inflammation
- Pluripotent Stem Cells Research
- Malaria Research and Control
- 3D Printing in Biomedical Research
- Inhalation and Respiratory Drug Delivery
- Complement system in diseases
- Innovative Microfluidic and Catalytic Techniques Innovation
- Cancer Genomics and Diagnostics
- Cytokine Signaling Pathways and Interactions
- Single-cell and spatial transcriptomics
- Chemokine receptors and signaling
- Epigenetics and DNA Methylation
- Mosquito-borne diseases and control
- Nanoparticle-Based Drug Delivery
- Computational Drug Discovery Methods
Massachusetts Institute of Technology
2015-2024
Howard Hughes Medical Institute
2014-2024
Harvard University
1991-2024
Allen Institute
2021-2024
Koch Institute for Integrative Cancer Research At MIT
2021-2024
Harvard–MIT Division of Health Sciences and Technology
2014-2021
Massachusetts General Hospital
1991-2008
Center for Neuroscience and Regenerative Medicine
2008
Harvard Stem Cell Institute
2005-2008
Princess Margaret Cancer Centre
2001-2004
The ability to remotely trigger CRISPR/Cas9 activity would enable new strategies study cellular events with greater precision and complexity. In this work, we have developed a method photocage the of guide RNA called "CRISPR-plus" (CRISPR-precise light-mediated unveiling sgRNAs). photoactivation capability our CRISPR-plus is compatible simultaneous targeting multiple DNA sequences supports numerous modifications that can labeling for use in imaging mechanistic investigations.
Liquid biopsies enable early detection and monitoring of diseases such as cancer, but their sensitivity remains limited by the scarcity analytes cell-free DNA (cfDNA) in blood. Improvements to have primarily relied on enhancing sequencing technology ex vivo. We sought transiently augment level circulating tumor (ctDNA) a blood draw attenuating its clearance report two intravenous priming agents given 1 2 hours before recover more ctDNA. Our consist nanoparticles that act cells responsible...
Synthetic biomarkers, bioengineered sensors that generate molecular reporters in diseased microenvironments, represent an emerging paradigm precision diagnostics. Despite the utility of DNA barcodes as a multiplexing tool, their susceptibility to nucleases vivo has limited utility. Here we exploit chemically stabilized nucleic acids multiplex synthetic biomarkers and produce diagnostic signals biofluids can be 'read out' via CRISPR nucleases. The strategy relies on microenvironmental...
The adaptor protein Lnk, and the closely related proteins APS SH2B, form a subfamily of SH2 domain-containing implicated in growth factor, cytokine, immunoreceptor signaling. To elucidate physiological function we derived Lnk-deficient mice. Lnk(-/-) mice are viable, but display marked changes hematopoietic compartment, including splenomegaly abnormal lymphoid myeloid homeostasis. vitro proliferative capacity absolute numbers progenitors from greatly increased, part due to hypersensitivity...
An engineered microenvironment supports expansion of adult human liver tissue after implantation in a mouse model injury.
The unique relapsing nature of Plasmodium vivax infection is a major barrier to malaria eradication. Upon infection, dormant liver-stage forms, hypnozoites, linger for weeks months and then relapse cause recurrent blood-stage infection. Very little known about hypnozoite biology; definitive biomarkers are lacking in vitro platforms that support phenotypic studies needed. Here, we recapitulate the entire liver stage P. vitro, using multiwell format incorporates micropatterned primary human...
Magnetically controlled synthetic and living micropropellers stir up nanoparticles for enhanced drug transport.
Lung cancer is the leading cause of cancer-related death, and patients most commonly present with incurable advanced-stage disease. U.S. national guidelines recommend screening for high-risk low-dose computed tomography, but this approach has limitations including high false-positive rates. Activity-based nanosensors can detect dysregulated proteases in vivo release a reporter to provide urinary readout disease activity. Here, we demonstrate translational potential activity-based lung by...
Malaria-causing Plasmodium vivax parasites can linger in the human liver for weeks to years and reactivate cause recurrent blood-stage infection. Although they are an important target malaria eradication, little is known about molecular features of replicative non-replicative intracellular liver-stage their host cell dependence. Here, we leverage a bioengineered microliver platform culture patient-derived P. transcriptional profiling. Coupling enrichment strategies with bulk single-cell...
Antimicrobial peptides (AMPs) constitute a promising class of alternatives to antibiotics curb antimicrobial resistance. Nonetheless, their utility as systemic agent is hampered by short circulation time and toxicity. Infection sites, analogous tumors, harbor an aberrant microenvironment that has the potential be exploited develop conditionally activated therapeutics with improved therapeutic index. In particular, we identified strategies prolong small, cationic AMPs in mouse model bacterial...
Liver regeneration is a well-orchestrated process that typically studied in animal models. Although previous studies have offered many insights into liver regeneration, human biology less well understood. To this end, we developed three-dimensional (3D) platform called structurally vascularized hepatic ensembles for analyzing (SHEAR) to model multiple aspects of regeneration. SHEAR enables control over hemodynamic alterations mimic those occur during injury and supports the administration...
Critical aspects of physiology and cell function exhibit self-sustained ~24-hour variations termed circadian rhythms. In the liver, rhythms play fundamental roles in maintaining organ homeostasis. Here, we established characterized an vitro liver experimental system which primary human hepatocytes display oscillations. By generating gene expression profiles these over time, demonstrated that their transcriptional state is dynamic across 24 hours identified a set cycling genes with functions...
The IL-7R and the pre-B cell receptor (pre-BCR) each provide critical signals during differentiation of B precursors. In this study we examine interplay between dependent upon these receptors. We demonstrate that pre-BCR-deficient pro-B cells differ significantly from controls in their ability to use IL-7R. show difference, characterized by a failure proliferate response IL-7, is narrowly restricted IL-7 concentrations picogram per milliliter range can be overcome with increasing amounts...
Although low-dose computed tomography screening improves lung cancer survival in at-risk groups, inequality remains diagnosis due to limited access and high costs of medical imaging infrastructure. We designed a needleless imaging-free platform, termed PATROL (point-of-care aerosolizable nanosensors with tumor-responsive oligonucleotide barcodes), reduce resource disparities for early detection cancer. formulates set DNA-barcoded, activity-based (ABNs) into an inhalable format. Lung...
RNA interference (RNAi) therapeutics are an emerging class of medicines that selectively target mRNA transcripts to silence protein production and combat disease. Despite the recent progress, a generalizable approach for monitoring efficacy RNAi without invasive biopsy remains challenge. Here, we describe development self-reporting, theranostic nanoparticle delivers siRNA drives cancer progression while also functional activity its downstream targets. Our therapeutic is transcription factor...
A tandem peptide-lipid based nanocomplexation strategy for targeted delivery of CRISPR/Cas9 in cells efficient gene editing.