Training the next generation of biomedical investigators in glycosciences

Agre, Peter; Bertozzi, Carolyn R.; Bissell, Mina J.; Campbell, Kevin P.; Cummings, Richard D.; Desai, Umesh R.; Estes, Mary K.; Flotte, Terence R.; Fogleman, Guy; Gage, Fred H.; Ginsburg, David; Gordon, Jeffrey I.; Hart, Gerald W.; Hascall, Vincent C.; Kiessling, Laura L.; Kornfeld, Stuart; Lowe, John J.; Magnani, John L.; Mahal, Lara K.; Medzhitov, Ruslan; Roberts, Richard J.; Sackstein, Robert; Sarkar, Rita; Schnaar, Ronald L.; Schwartz, Nancy B.; Varki, Ajit; Walt, David R.; Weissman, Irving

doi:10.1172/jci85905

Cited by 34 publications

(57 citation statements)

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“…In general, glycomic studies on cancer to date fall short of pinpointing enzymes responsible for the biosynthesis of observed aberrant glycan motifs and/or their relevant glycoprotein targets (Sugahara et al, 2012). Glycosylation remains an understudied portion of cancer biology due to issues including difficulties in glycan analysis and complex biosynthetic pathways (Agre et al, 2016; Rakus and Mahal, 2011). …”

Section: Introductionmentioning

confidence: 99%

A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis

et al. 2017

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SUMMARY Association of aberrant glycosylation with melanoma progression is based mainly on analyses of cell lines. Here we present a systems-based study of glycomic changes and corresponding enzymes associated with melanoma metastasis in patient samples. Upregulation of core fucosylation (FUT8) and downregulation of α-1,2 fucosylation (FUT1, FUT2) were identified as features of metastatic melanoma. Using both in vitro and in vivo studies, we demonstrate FUT8 is a driver of melanoma metastasis which, when silenced, suppresses invasion and tumor dissemination. Glycoprotein targets of FUT8 were enriched in cell migration proteins including the adhesion molecule L1CAM. Core fucosylation impacted L1CAM cleavage and the ability of L1CAM to support melanoma invasion. FUT8 and its targets represent therapeutic targets in melanoma metastasis.

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Section: Introductionmentioning

confidence: 99%

A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis

et al. 2017

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“…It is harvested from porcine intestine and processed into a pharmaceutical grade product in what is arguably one of the most uncontrolled pharmaceutical processes, yet yielding an approved drug that is largely very safe. Indeed, glycoscience training, identified by the National Institutions of Health (NIH) as an important gap in biology curricula, [1] is essential for the industry to shift this conceptual focus to better embrace the opportunities afforded by the multiple interactions of glycans, and thus their potential for robust targeting of multiple mechanisms-a single agent that is itself a combination therapy. This is an extremely narrow characterization, however, given that heparin interacts with over 400 known human proteins.…”

Section: ) Clinical Relevance Current Developments and Validating mentioning

confidence: 99%

“…Zucero Therapeutics, based in Australia, is developing PG545 (pixatimod) (Figure 1), which is a fully sulfated α-D- [1][2][3][4]glucopyranose tetrasaccharide, inspired by heparin; this sulfated polysaccharide is appended with a hydrophobic 3-cholestanyl group in order to improve its half-life. The mechanism of this novel immunomodulatory molecule is stimulation of the innate immune response to tumors.…”

Section: Zucero Therapeuticsmentioning

confidence: 99%

“…[1] This lapse is not for lack of therapeutic potential or biological relevance; however, rather a consequence of the drug classes that were realized in the 1970s, kicked off by recombinant protein therapeutics. As described in detail by a working group supported by the National Heart, Lung and Blood Institute (NHLBI), glycans have become the "dark matter" of biology and have gone largely ignored for decades.…”

Section: Introductionmentioning

confidence: 99%

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Glycan Therapeutics: Resurrecting an Almost Pharma‐Forgotten Drug Class

Paderi¹,

Prestwich

Panitch

et al. 2018

Advanced Therapeutics

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Despite their enormous potential, glycans as therapeutics yet remain a widely untapped drug class. This overview shares the viewpoint that glycans have been aptly termed the "dark matter" of biology and have thus been largely ignored for decades. Provided herein is a background on the multiple structures and functions of glycan therapeutics, and focuses on examples and case studies of the glycan therapeutics in clinical use or in a clinical development. Perspectives on various hurdles are also provided, such as regulatory or scientific messaging and how these can influence the clinical development of this drug category. Finally some of the necessary changes in perception, education, and research infrastructure for continued support and advancement of this promising category of therapeutics are described.

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“…Low glucose level can revert a malignant phenotype. In this context, she promotes centers of excellence for training the next generation of biomedical investigators in the glycosciences [16] .…”

Section: Tumor-host Microenvironment Interaction and Metabolismmentioning

confidence: 99%

Personalized Cancer Care: Risk Prediction, Early Diagnosis, Progression, and Therapy

Zänker

Børresen‐Dale

2016

Biomed Hub

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At the annual prestigious International Symposium of the Fritz-Bender Foundation, Munich, 18-20 May, 2016, researchers, clinicians, and students discussed the state of the art and future perspectives of genomic medicine in cancer. Genomic medicine (also known as precision medicine/oncology) should help clinicians to provide a more precise diagnosis and therapy in oncology for individual patients. The meeting focused on next-generation sequencing methods, analytical computational analysis of big data, and data mining on the way to translational and evidence-based medicine. The meeting covered the social and ethical impact of genomic medicine as well as news and views on antibody targeting of intracellular proteins, on the architecture of intracellular proteins and their impact on carcinogenesis, and on the adaptation of tumor therapy in due consideration of tumor evolution. Subheadings like "Genetic Profiling of Patients and Risk Prediction," "Molecular Profiling of Tumors and Metastases," "Tumor-Host Microenvironment Interaction and Metabolism," and "Targeted Therapy" were subsumed under the main heading of "Personalized Cancer Care." What Is It about?This meeting report is a follow-up progress report from a previous one in 2013. It summarizes at the cutting edge how cancer manifests in the human body. Basic scientists and clinicians shared their views on personal cancer care and precision cancer medicine with special reference to epigenetic, genetic, and novel therapy strategies.

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Training the next generation of biomedical investigators in glycosciences

Cited by 34 publications

References 0 publications

A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis

A Systems Biology Approach Identifies FUT8 as a Driver of Melanoma Metastasis

Glycan Therapeutics: Resurrecting an Almost Pharma‐Forgotten Drug Class

Personalized Cancer Care: Risk Prediction, Early Diagnosis, Progression, and Therapy

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