A5040615633- Glycosylation and Glycoproteins Research
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Cell Adhesion Molecules Research
- RNA Interference and Gene Delivery
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Cellular Mechanics and Interactions
- Immune cells in cancer
- Genomics and Phylogenetic Studies
- Phagocytosis and Immune Regulation
- Ion Transport and Channel Regulation
- Pancreatic function and diabetes
- Acute Lymphoblastic Leukemia research
- Metabolism and Genetic Disorders
- Caveolin-1 and cellular processes
- Bacteriophages and microbial interactions
- Cellular transport and secretion
- Mathematical Biology Tumor Growth
- Barrier Structure and Function Studies
- vaccines and immunoinformatics approaches
- Chemokine receptors and signaling
- Proteoglycans and glycosaminoglycans research
Massachusetts General Hospital
2022-2025
Center for Cancer Research
2025
Harvard University
2025
Children's Hospital of Philadelphia
2009-2023
Stanford University
2016-2020
Palo Alto University
2017-2019
University of California, Berkeley
2013-2018
Howard Hughes Medical Institute
2016-2018
Significance Successful tumors are able to evade the immune system, which is otherwise capable of killing transformed cells. Therapies that prevent this evasion have become revolutionary treatments for incurable cancers. One mechanism presentation sugars, called sialic acids, within cell surface’s sugar coating, or glycocalyx. Here, we designed biotherapeutic molecules, termed “antibody–enzyme conjugates,” selectively remove acids from tumor The antibody directs enzyme cancer cells, cleaves...
Mucin domains are densely O-glycosylated modular protein that found in a wide variety of cell surface and secreted proteins. Mucin-domain glycoproteins known to be key players host human diseases, especially cancer, wherein mucin expression glycosylation patterns altered. biology has been difficult study at the molecular level, part, because methods manipulate structurally characterize lacking. Here, we demonstrate protease C1 esterase inhibitor (StcE), bacterial from Escherichia coli,...
Synthetic glycopolymers that emulate cell-surface mucins have been used to elucidate the role of mucin overexpression in cancer. However, because they are internalized within hours, these could not be employed probe processes occur on longer time scales. In this work, we tested a panel bearing variety lipids identify those persist cell membranes. Strikingly, found cholesterylamine (CholA) anchored into vesicles serve as depots for delivery back surface, allowing display at least ten days,...
Metastasis depends upon cancer cell growth and survival within the metastatic niche. Tumors which remodel their glycocalyces, by overexpressing bulky glycoproteins like mucins, exhibit a higher predisposition to metastasize, but role of mucins in oncogenesis remains poorly understood. Here we report that glycocalyx promotes expansion disseminated tumor cells vivo fostering integrin adhesion assembly permit G1 cycle progression. We engineered display glycocalyces various thicknesses coating...
Many cancer patients treated with immune checkpoint blockade (ICB) do not have durable treatment responses. Circulating biomarkers the potential to identify primary resistance or early progression on therapy alter course and avoid unnecessary toxicity. Unbiased multimodal proteomic profiling in blood has been underexplored due previously limited scalability of multiplexing technologies cohorts lacking time-series sampling. To address this, we performed plasma >2,900 proteins...
Abstract Macrophages in the tumor microenvironment exert potent anti-tumorigenic activity through phagocytosis. Yet therapeutics that enhance macrophage phagocytosis have not improved outcomes clinical trials for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). To systematically identify regulators of phagocytosis, we performed genome-scale CRISPR knockout screens human cells co-cultured monocyte-derived macrophages. Surprisingly, found whereas classic “don’t eat...
ABSTRACT The standard of care in high-grade gliomas has remained unchanged the past 20 years. Efforts to replicate effective immunotherapies non-cranial tumors have led only modest therapeutical improvements glioblastoma (GB). Here, we demonstrate that intratumoral administration recombinant interleukin-12 (rIL-12) promotes local cytotoxic CD8 POS T cell accumulation and conversion into an effector-like state, resulting a dose-dependent survival benefit preclinical GB mouse models. This...
Abstract Synthetic glycopolymers that emulate cell‐surface mucins have been used to elucidate the role of mucin overexpression in cancer. However, because they are internalized within hours, these could not be employed probe processes occur on longer time scales. In this work, we tested a panel bearing variety lipids identify those persist cell membranes. Strikingly, found cholesterylamine (CholA) anchored into vesicles serve as depots for delivery back surface, allowing display at least ten...
Abstract: Sera from 138 patients who had experienced hypersensitivity‐type reactions while on hemodialysis (reactors) were examined retrospectively by the radioal‐lergosorbent test (RAST) for specific IgE antibody to ethylene oxide (ETO). Seventy‐eight without a history of reaction also evaluated as controls. Elevated serum RAST values (> 2.0) more common in reactors (63%) than controls (11%, p < 0.001). In second study, assays performed using human albumin conjugated ETO (HSA‐ETO)...
Acidosis causes millions of deaths each year and strategies for normalizing the blood pH in acidosis patients are greatly needed. The lactate dehydrogenase (LDH) pathway has great potential treating due to its ability convert protons pyruvate into thereby raise pH, but been challenging develop a therapy because there no pharmaceutical-based approaches engineering metabolic pathways vivo. In this report we demonstrate that flux LDH can be engineered with compound 5-amino-2-hydroxymethylphenyl...
Currently approved immune checkpoint inhibitor (ICI) therapies targeting the PD-1 and CTLA-4 receptor pathways are powerful treatment options for certain cancers; however, majority of patients across cancer types still fail to respond. Addressing alternative that mediate suppression could enhance ICI efficacy. One such mechanism is increase in sialic acid-containing proteins lipids (sialoglycans) malignancy, which recently has been shown inhibit cell activation through multiple mechanisms...
Abstract Most patients treated with immune checkpoint blockade (ICB) do not have durable treatment responses. Therefore, there is a critical need to identify early non-invasive biomarkers of response. We performed plasma proteomic analysis (>700 proteins) at three timepoints on 174 metastatic melanoma ICB. leverage independent training and testing cohorts build predictor immunotherapy response that outperforms several tissue-based approaches. found 217 differentially expressed proteins...
Currently approved immune checkpoint inhibitor (ICI) therapies targeting the PD-1 and CTLA-4 receptor pathways are powerful treatment options for certain cancers; however, majority of patients across cancer types still fail to respond. Addressing alternative that mediate suppression could enhance ICI efficacy. One such mechanism is increase in sialic acid-containing proteins lipids (sialoglycans) malignancy, which recently has been shown inhibit cell activation through multiple mechanisms...
Mucins are a class of highly O-glycosylated proteins that ubiquitously expressed on cellular surfaces and important for human health, especially in the context carcinomas. However, molecular mechanisms by which aberrant mucin structures lead to tumor progression immune evasion have been slow come light, part because methods selective degradation lacking. Here we employ high resolution mass spectrometry, polymer synthesis, computational peptide docking demonstrate bacterial protease, called...
<div><div><div><p>Currently approved immune checkpoint inhibitor (ICI) therapies targeting the PD-1 and CTLA-4 receptor pathways are powerful treatment options for certain cancers; however, majority of patients across cancer types still fail to respond. Addressing alternative that mediate suppression could enhance ICI efficacy. One such mechanism is increase in sialic acid-containing proteins lipids (sialoglycans) malignancy, which recently has been shown inhibit cell...
Abstract This abstract is being presented as a short talk in the scientific program. A full printed Proffered Abstracts section (PR018) of Conference Program/Proceedings. Citation Format: Samuel J. Wright, Izabella Zamora, Milan Parikh, Deepika Yeramosu, Lynn Bi, Sarah Kang, Marijana Rucevic, Moshe Sade-Feldman, Baolin Liu, Ngan Nguyen, Jamey Guess, Alexis Schneider, David Lieb, Elliot Woods, William Michaud, Aleigha R. Lawless, Tatyana Sharova, Gyulnara Kasumova, Michelle S. Kim, Ryan Park,...
Abstract Most patients treated with immune checkpoint blockade (ICB) do not have durable treatment responses, stressing a critical need to identify early non-invasive biomarkers of response. Circulating provide easy access for serial monitoring and can insight on the mechanisms response ICB. We performed plasma proteomics (2943 proteins) 250 metastatic melanoma before ICB analysis response- time point-associated peripheral protein biomarkers. next generated patient- matched blood lymphocyte...