A5029714883- CAR-T cell therapy research
- Transboundary Water Resource Management
- Immunotherapy and Immune Responses
- Virus-based gene therapy research
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- International Maritime Law Issues
- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Phagocytosis and Immune Regulation
- Water resources management and optimization
- Water-Energy-Food Nexus Studies
- Animal Virus Infections Studies
- Viral Infections and Immunology Research
- Cytomegalovirus and herpesvirus research
- Advanced Biosensing Techniques and Applications
- RNA Interference and Gene Delivery
- Immune cells in cancer
- Hematological disorders and diagnostics
- Mesenchymal stem cell research
- Arctic and Russian Policy Studies
- Global Energy Security and Policy
- Intestinal and Peritoneal Adhesions
- Cancer Research and Treatments
Tufts University
2021-2025
University of California, San Diego
2023
Oregon State University
2018-2023
University of Rhode Island
2023
Scripps Institution of Oceanography
2023
Stanford University
2015-2021
Institute for Stem Cell Biology and Regenerative Medicine
2019
Batumi Navigation Teaching University
2018
World Bank Group
2018
University of California, Los Angeles
2012-2017
Significance Programmed cell death protein-1 (PD-1) and programmed ligand-1 (PD-L1) are key targets in the treatment of cancer, but current antibody-based drugs against this pathway have inherent drawbacks that may limit their effectiveness. We used directed evolution with yeast display to engineer a nonantibody biologic based on ectodomain PD-1. High-affinity PD-1 was more effective than anti–PD-L1 antibodies mouse tumor models could additionally be as PET imaging tracer noninvasively...
Tumor-associated macrophages (TAMs) represent an important cellular subset within the glioblastoma (WHO grade IV) microenvironment and are a potential therapeutic target. TAMs display continuum of different polarization states between antitumorigenic M1 protumorigenic M2 phenotypes, with lower M1/M2 ratio correlating worse prognosis. Here, we investigated effect macrophage on anti-CD47 antibody-mediated phagocytosis human cells in vitro, as well distribution versus grown mouse xenografts....
Abstract The rapidly advancing field of cancer immunotherapy is currently limited by the scarcity noninvasive and quantitative technologies capable monitoring presence abundance CD8+ T cells other immune cell subsets. In this study, we describe generation 89Zr-desferrioxamine–labeled anti-CD8 cys-diabody (89Zr-malDFO-169 cDb) for immuno-PET tracking endogenous cells. We demonstrate that a sensitive tool detecting changes in systemic tumor-infiltrating CD8 expression preclinical syngeneic...
Abstract Recent advances with immunotherapy agents for the treatment of cancer have provided remarkable, and in some cases, curative results. Our laboratory has identified CD47 as an important “don't eat me” signal expressed on malignant cells. Blockade CD47:SIRP-α axis between tumor cells innate immune (monocytes, macrophages, dendritic cells) increases cell phagocytosis both solid tumors (including, but not limited to, bladder, breast, colon, lung, pancreatic) hematologic malignancies....
Significance Anti-CD8 immuno-PET imaging agents provide the potential to monitor localization, migration, and expansion of CD8-expressing cells noninvasively in vivo. Shown here is successful generation functional anti-CD8 based on engineered antibodies for use a variety preclinical disease immunotherapeutic models.
The delineation of the world’s international river basins has not been undertaken by any formal body since 1978. Researchers with Transboundary Freshwater Dispute Database have attempted to fill this void through 1999 Register, online updates and currently present study. This current register delineates 310 basins, reflecting changes in political boundaries increased data quality. These are shared 150 countries disputed areas, cover 47.1% Earth’s land surface include 52% population. paper...
The proliferation and trafficking of T lymphocytes in immune responses are crucial events determining inflammatory responses. To study whole-body lymphocyte dynamics noninvasively vivo, we generated anti-CD4 -CD8 cys-diabodies (cDbs) derived from the parental antibody hybridomas GK1.5 2.43, respectively, for (89)Zr-immuno-PET detection helper cytotoxic cell populations.Anti-CD4 cDbs were engineered, produced via mammalian expression, purified using immobilized metal affinity chromatography,...
Immune checkpoint blockade has emerged as a promising cancer treatment paradigm. Unfortunately, there are still large number of patients and malignancies that do not respond to therapy. A major barrier validating biomarkers for the prediction monitoring responders clinical been lack imaging tools accurately assess dynamic immune expression. Here, we sought optimize noninvasive immuno-PET human programmed death-ligand 1 (PD-L1) expression, in preclinical model, using small high-affinity...
Peritoneal adhesions are fibrous tissues that tether organs to one another or the peritoneal wall and a major cause of postsurgical infectious morbidity. The primary molecular chain events leading initiation has been elusive, chiefly due lack an identifiable cell origin. Using clonal analysis lineage tracing, we have identified injured surface mesothelium expressing podoplanin (PDPN) mesothelin (MSLN) as instigator after surgery in mice. We demonstrate anti-MSLN antibody diminished adhesion...
This article explores major findings and evolutions in understandings of transboundary water conflict cooperation over the last three decades, focusing on trends emerging from Transboundary Freshwater Diplomacy Database. It is found that since 1940s, countries tend to cooperate shared resources, contrast media portrayals 'water wars'. Water conflicts, which have increased slightly 2000, are mostly fuelled by quantity disputes or unilateral infrastructure developments. Institutions play a...
Key Points Upon injury, the mesothelium recruits neutrophils to peritoneal space, which contributes adhesion formation. Neutrophil recruitment and macrophage-depletion kinetics in adhesions differ from normal innate response.
Positron emission tomography (PET) reporter genes allow noninvasive whole-body imaging of transplanted cells by detection with radiolabeled probes. We used a human deoxycytidine kinase containing three amino acid substitutions within the active site (hdCK3mut) as gene in combination PET probe [ 18 F]-L-FMAU (1-(2-deoxy-2- fluoro-β-L-arabinofuranosyl)-5-methyluracil) to monitor models mouse and hematopoietic stem cell (HSC) transplantation. These mutations hdCK3mut expanded substrate capacity...
Adoptive transfer of tumor-reactive T cells can successfully reduce tumor burden; however, in rare cases, lethal on-target/off-tumor effects have been reported. A noninvasive method to track engineered with high sensitivity and resolution would allow observation correct cell homing and/or identification dangerous off-target locations preclinical clinical applications. Human deoxycytidine kinase triple mutant (hdCK3mut) is a nonimmunogenic PET reporter that was previously shown be an...
Abstract Engineering immunity against cancer by the adoptive transfer of hematopoietic stem cells (HSC) modified to express antigen-specific T-cell receptors (TCR) or chimeric antigen generates a continual supply effector T cells, potentially providing superior anticancer efficacy compared with infusion terminally differentiated cells. Here, we demonstrate in vivo generation functional from CD34-enriched human peripheral blood lentiviral vector designed for clinical use encoding TCR...
<h3>Background:</h3> Colistin is often used as an antimicrobial of last resort for the treatment infections caused by multidrug-resistant gram-negative bacilli. In 2015, plasmid-mediated colistin resistance in <i>Escherichia coli</i> due to MCR-1 was described. The purpose this study evaluate frequency among <i>E. clinical isolates obtained from patients Canadian hospitals part Ward Surveillance Study (CANWARD) and determine how <i>mcr-1</i> gene detected colistin-resistant subset....
Efficient and adequate generation of deoxyribonucleotides is critical to successful DNA repair. We show that ataxia telangiectasia mutated (ATM) integrates the damage response with metabolism by regulating salvage deoxyribonucleosides. Specifically, ATM phosphorylates activates deoxycytidine kinase (dCK) at serine 74 in ionizing radiation (IR). Activation dCK shifts its substrate specificity toward deoxycytidine, increases intracellular dCTP pools post IR, enhances rate Mutation a single...
Significance The saccharide ribose is naturally present in food and circulates the blood. Previous studies suggest that cells internalize directly from extracellular space, but how, why, where this occurs body are not well understood. Here, we developed a new PET probe to monitor process vivo. Using [ 14 C]ribose, show salvage concentrated liver. We identify solute carrier family 2, member 2 one of potentially several transporters. demonstrate down-regulated during metabolic syndrome. This...
Much has been written on hydropolitics, or the interplays between transboundary water resource issues and politics. This article builds recent calls for more research role of discourses in shaping hydropolitics. We propose a conceptual framework, inspired by critical discourse analysis, systematic investigation how discursive practices construct enact actors' power positions basin governance. Our framework's added value lies typology we develop – that is, dominant, institutionalized,...
The forest transition model posits that as a society advances to later stages of demographic and economic transitions, reforestation begins outpace deforestation. However, this concept was constructed on endogenous factors within more developed nation‐states, giving scant attention exogenous today's globalising world has made increasingly relevant. Further, the period between net deforestation needs be better understood, particularly in developing countries may going through transition. Here...