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10 results on '"Michelle K. Jewett"'

1. Table S3 from The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis

Author

Daniel A. Haber, Shyamala Maheswaran, Gad Getz, Shannon L. Stott, Mehmet Toner, David T. Ting, Anders M. Näär, Nir Hacohen, Linda T. Nieman, Michelle K. Jewett, Katherine Calhoun, Laxmi Parida, Samuel S. Freeman, Risa Burr, François Aguet, Chenyue Lu, Todd Bonesteel, Dieuwke L. Marvin, Genevieve M. Boland, Elad Horwitz, Benjamin Wesley, Moshe Sade-Feldman, Taronish D. Dubash, Hongshan Guo, Ben S. Wittner, Keith H.K. Wong, Ryan J. Sullivan, Whijae Roh, and Xin Hong

Abstract

Table S3

Published
2023
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2. Table S8 from The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis

Author

Daniel A. Haber, Shyamala Maheswaran, Gad Getz, Shannon L. Stott, Mehmet Toner, David T. Ting, Anders M. Näär, Nir Hacohen, Linda T. Nieman, Michelle K. Jewett, Katherine Calhoun, Laxmi Parida, Samuel S. Freeman, Risa Burr, François Aguet, Chenyue Lu, Todd Bonesteel, Dieuwke L. Marvin, Genevieve M. Boland, Elad Horwitz, Benjamin Wesley, Moshe Sade-Feldman, Taronish D. Dubash, Hongshan Guo, Ben S. Wittner, Keith H.K. Wong, Ryan J. Sullivan, Whijae Roh, and Xin Hong

Abstract

Table S8

Published
2023
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3. Supplementary Data from The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis

Author

Daniel A. Haber, Shyamala Maheswaran, Gad Getz, Shannon L. Stott, Mehmet Toner, David T. Ting, Anders M. Näär, Nir Hacohen, Linda T. Nieman, Michelle K. Jewett, Katherine Calhoun, Laxmi Parida, Samuel S. Freeman, Risa Burr, François Aguet, Chenyue Lu, Todd Bonesteel, Dieuwke L. Marvin, Genevieve M. Boland, Elad Horwitz, Benjamin Wesley, Moshe Sade-Feldman, Taronish D. Dubash, Hongshan Guo, Ben S. Wittner, Keith H.K. Wong, Ryan J. Sullivan, Whijae Roh, and Xin Hong

Abstract

Supplementary Information

Published
2023
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4. Table S2 from The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis

Author

Daniel A. Haber, Shyamala Maheswaran, Gad Getz, Shannon L. Stott, Mehmet Toner, David T. Ting, Anders M. Näär, Nir Hacohen, Linda T. Nieman, Michelle K. Jewett, Katherine Calhoun, Laxmi Parida, Samuel S. Freeman, Risa Burr, François Aguet, Chenyue Lu, Todd Bonesteel, Dieuwke L. Marvin, Genevieve M. Boland, Elad Horwitz, Benjamin Wesley, Moshe Sade-Feldman, Taronish D. Dubash, Hongshan Guo, Ben S. Wittner, Keith H.K. Wong, Ryan J. Sullivan, Whijae Roh, and Xin Hong

Abstract

Table S2

Published
2023
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5. Table S7 from The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis

Author

Daniel A. Haber, Shyamala Maheswaran, Gad Getz, Shannon L. Stott, Mehmet Toner, David T. Ting, Anders M. Näär, Nir Hacohen, Linda T. Nieman, Michelle K. Jewett, Katherine Calhoun, Laxmi Parida, Samuel S. Freeman, Risa Burr, François Aguet, Chenyue Lu, Todd Bonesteel, Dieuwke L. Marvin, Genevieve M. Boland, Elad Horwitz, Benjamin Wesley, Moshe Sade-Feldman, Taronish D. Dubash, Hongshan Guo, Ben S. Wittner, Keith H.K. Wong, Ryan J. Sullivan, Whijae Roh, and Xin Hong

Abstract

Table S7

Published
2023
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6. Table S5 from The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis

Author

Daniel A. Haber, Shyamala Maheswaran, Gad Getz, Shannon L. Stott, Mehmet Toner, David T. Ting, Anders M. Näär, Nir Hacohen, Linda T. Nieman, Michelle K. Jewett, Katherine Calhoun, Laxmi Parida, Samuel S. Freeman, Risa Burr, François Aguet, Chenyue Lu, Todd Bonesteel, Dieuwke L. Marvin, Genevieve M. Boland, Elad Horwitz, Benjamin Wesley, Moshe Sade-Feldman, Taronish D. Dubash, Hongshan Guo, Ben S. Wittner, Keith H.K. Wong, Ryan J. Sullivan, Whijae Roh, and Xin Hong

Abstract

Table S5

Published
2023
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7. Table S4 from The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis

Author

Daniel A. Haber, Shyamala Maheswaran, Gad Getz, Shannon L. Stott, Mehmet Toner, David T. Ting, Anders M. Näär, Nir Hacohen, Linda T. Nieman, Michelle K. Jewett, Katherine Calhoun, Laxmi Parida, Samuel S. Freeman, Risa Burr, François Aguet, Chenyue Lu, Todd Bonesteel, Dieuwke L. Marvin, Genevieve M. Boland, Elad Horwitz, Benjamin Wesley, Moshe Sade-Feldman, Taronish D. Dubash, Hongshan Guo, Ben S. Wittner, Keith H.K. Wong, Ryan J. Sullivan, Whijae Roh, and Xin Hong

Abstract

Table S4

Published
2023
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8. Table S6 from The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis

Author

Daniel A. Haber, Shyamala Maheswaran, Gad Getz, Shannon L. Stott, Mehmet Toner, David T. Ting, Anders M. Näär, Nir Hacohen, Linda T. Nieman, Michelle K. Jewett, Katherine Calhoun, Laxmi Parida, Samuel S. Freeman, Risa Burr, François Aguet, Chenyue Lu, Todd Bonesteel, Dieuwke L. Marvin, Genevieve M. Boland, Elad Horwitz, Benjamin Wesley, Moshe Sade-Feldman, Taronish D. Dubash, Hongshan Guo, Ben S. Wittner, Keith H.K. Wong, Ryan J. Sullivan, Whijae Roh, and Xin Hong

Abstract

Table S6

Published
2023
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9. The Lipogenic Regulator SREBP2 Induces Transferrin in Circulating Melanoma Cells and Suppresses Ferroptosis

Author

Anders M. Näär, Benjamin Wesley, Keith H. K. Wong, Moshe Sade-Feldman, Elad Horwitz, Whijae Roh, Gad Getz, David T. Ting, Linda T. Nieman, Shyamala Maheswaran, Samuel S. Freeman, Daniel A. Haber, Genevieve M. Boland, Xin Hong, Taronish D. Dubash, Katherine Calhoun, Hongshan Guo, Dieuwke L. Marvin, Mehmet Toner, Ben S. Wittner, Nir Hacohen, Michelle K. Jewett, Shannon L. Stott, Chenyue Lu, Laxmi Parida, Todd Bonesteel, François Aguet, Ryan J. Sullivan, and Risa Burr

Subjects
0301 basic medicine, medicine.disease_cause, Article, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Circulating tumor cell, Downregulation and upregulation, Biomarkers, Tumor, medicine, Ferroptosis, Humans, Melanoma, Cells, Cultured, chemistry.chemical_classification, Gene knockdown, Chemistry, Lipogenesis, Transferrin, Neoplastic Cells, Circulating, medicine.disease, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Mutation, Cancer research, Disease Susceptibility, Single-Cell Analysis, Oxidative stress, Signal Transduction, Sterol Regulatory Element Binding Protein 2
Abstract

Circulating tumor cells (CTC) are shed by cancer into the bloodstream, where a viable subset overcomes oxidative stress to initiate metastasis. We show that single CTCs from patients with melanoma coordinately upregulate lipogenesis and iron homeostasis pathways. These are correlated with both intrinsic and acquired resistance to BRAF inhibitors across clonal cultures of BRAF-mutant CTCs. The lipogenesis regulator SREBP2 directly induces transcription of the iron carrier Transferrin (TF), reducing intracellular iron pools, reactive oxygen species, and lipid peroxidation, thereby conferring resistance to inducers of ferroptosis. Knockdown of endogenous TF impairs tumor formation by melanoma CTCs, and their tumorigenic defects are partially rescued by the lipophilic antioxidants ferrostatin-1 and vitamin E. In a prospective melanoma cohort, presence of CTCs with high lipogenic and iron metabolic RNA signatures is correlated with adverse clinical outcome, irrespective of treatment regimen. Thus, SREBP2-driven iron homeostatic pathways contribute to cancer progression, drug resistance, and metastasis. Significance: Through single-cell analysis of primary and cultured melanoma CTCs, we have uncovered intrinsic cancer cell heterogeneity within lipogenic and iron homeostatic pathways that modulates resistance to BRAF inhibitors and to ferroptosis inducers. Activation of these pathways within CTCs is correlated with adverse clinical outcome, pointing to therapeutic opportunities. This article is highlighted in the In This Issue feature, p. 521

Published
2021
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10. Ultrahigh-throughput magnetic sorting of large blood volumes for epitope-agnostic isolation of circulating tumor cells

Author

Nezihi Murat Karabacak, Michelle K. Jewett, Mehmet Toner, Daniel C. Rabe, Shyamala Maheswaran, Avanish Mishra, Daniel A. Haber, Suhaas G Garre, Jon F. Edd, Taronish D. Dubash, Baris R. Mutlu, John R. Walsh, Ravi Kapur, and Shannon L. Stott

Subjects
Medical Sciences, Microfluidics, Cell Separation, circulating tumor cells, Peripheral blood mononuclear cell, Epitope, Engineering, Circulating tumor cell, Nucleated cell, magnetic sorting, Cell Line, Tumor, Humans, Leukapheresis, Liquid biopsy, Multidisciplinary, liquid biopsy, Chemistry, Biological Sciences, Neoplastic Cells, Circulating, High-Throughput Screening Assays, Cell biology, Magnetic Fields, Physical Sciences, Cancer cell
Abstract

Significance Isolation of sufficient numbers of circulating tumor cells (CTCs) in cancer patients could provide an alternative to invasive tumor biopsies, providing multianalyte cell-based biomarkers that are not available from current plasma circulating tumor DNA sequencing. Given the average prevalence at one CTC per billion blood cells, very large blood volumes must be screened to provide enough CTCs for reliable clinical applications. By creating an ultrahigh-throughput magnetic sorter, we demonstrate the efficient removal of leukocytes from near whole blood volume equivalents. Combined with leukapheresis to initially concentrate blood mononuclear cells, this LPCTC-iChip platform will enable noninvasive sampling of cancer cells in sufficient numbers for clinical applications, ranging from real-time pharmacokinetic monitoring of drug response to tissue-of-origin determination in early-stage cancer screening., Circulating tumor cell (CTC)-based liquid biopsies provide unique opportunities for cancer diagnostics, treatment selection, and response monitoring, but even with advanced microfluidic technologies for rare cell detection the very low number of CTCs in standard 10-mL peripheral blood samples limits their clinical utility. Clinical leukapheresis can concentrate mononuclear cells from almost the entire blood volume, but such large numbers and concentrations of cells are incompatible with current rare cell enrichment technologies. Here, we describe an ultrahigh-throughput microfluidic chip, LPCTC-iChip, that rapidly sorts through an entire leukapheresis product of over 6 billion nucleated cells, increasing CTC isolation capacity by two orders of magnitude (86% recovery with 105 enrichment). Using soft iron-filled channels to act as magnetic microlenses, we intensify the field gradient within sorting channels. Increasing magnetic fields applied to inertially focused streams of cells effectively deplete massive numbers of magnetically labeled leukocytes within microfluidic channels. The negative depletion of antibody-tagged leukocytes enables isolation of potentially viable CTCs without bias for expression of specific tumor epitopes, making this platform applicable to all solid tumors. Thus, the initial enrichment by routine leukapheresis of mononuclear cells from very large blood volumes, followed by rapid flow, high-gradient magnetic sorting of untagged CTCs, provides a technology for noninvasive isolation of cancer cells in sufficient numbers for multiple clinical and experimental applications.

Published
2020
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