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Author M Toner

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Single cell proteomics of tumor compartments identifies differential kinase activities defining sensitivity to mTOR-PI3-kinase inhibition

Nezihi Murat Karabacak, Yu Zheng, Taronish Dubash, Risa Burr, Douglas Micalizzi, Ben Wittner, Devon Wiley, Valentine Comaills, Erin Emmons, Kira Niederhoffer, Uyen Ho, Linda Nieman, Wilhelm Haas, Shannon Stott, David Ting, David Miyamoto, Daniel Haber, Mehmet Toner, Shyamala Maheswaran,

<h4>ABSTRACT</h4> Cancer therapy often results in heterogeneous responses in different metastatic lesions in the same patient. Inter- and intra-tumor heterogeneity in proteomic signaling within the various tumor compartments and its impact on therapy are not well characterized due to the limited sensitivity of single cell proteomic approaches. To overcome this ... Read more >>

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Cryoprotectant toxicity and hypothermic sensitivity among Anopheles larvae.

Jenny E Nesbitt, Anisa Swei, Catherine Hunt, Ellen Dotson, Mehmet Toner, Rebecca D Sandlin,

Laboratory rearing of mosquitoes is commonly practiced by researchers studying mosquito-borne infectious diseases and vector control methods. In the absence of cryopreservation methods to stabilize unique or genetically modified strains, mosquito lines must be continuously maintained, a laborious process that risks selection effects, contamination, and genetic drift. Towards the development ... Read more >>

Cryobiology (Cryobiology)
[2020, :]

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HIF1A signaling selectively supports proliferation of breast cancer in the brain.

Richard Y Ebright, Marcus A Zachariah, Douglas S Micalizzi, Ben S Wittner, Kira L Niederhoffer, Linda T Nieman, Brian Chirn, Devon F Wiley, Benjamin Wesley, Brian Shaw, Edwin Nieblas-Bedolla, Lian Atlas, Annamaria Szabolcs, Anthony J Iafrate, Mehmet Toner, David T Ting, Priscilla K Brastianos, Daniel A Haber, Shyamala Maheswaran,

Blood-borne metastasis to the brain is a major complication of breast cancer, but cellular pathways that enable cancer cells to selectively grow in the brain microenvironment are poorly understood. We find that cultured circulating tumor cells (CTCs), derived from blood samples of women with advanced breast cancer and directly inoculated ... Read more >>

Nat Commun (Nature communications)
[2020, 11(1):6311]

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'Out of house' virtual surgical planning for mandible reconstruction after cancer resection: is it oncologically safe?

C P Barry, C MacDhabheid, K Tobin, L F Stassen, P Lennon, M Toner, E O'Regan, J R Clark,

The purpose of this study was to investigate whether the time delay between 'out of house' proprietary virtual surgical planning (OH-VSP) of the mandibular resection for oral cancer and the actual surgery results in compromised margins and oncological disadvantage for the patient. Outcomes of patients who had OH-VSP of their ... Read more >>

Int J Oral Maxillofac Surg (International journal of oral and maxillofacial surgery)
[2020, :]

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A common complaint… a rare disease!

Mary-Beth Toner, Seana Molloy, Peter Mallett, Andrew Thompson, Lynne Speirs,

A 2-year-old previously well child presented to the emergency department with temperatures and lethargy. He was pale and looked unwell. He received a fluid bolus and was commenced on intravenous ceftriaxone. Pus was discharging from his left ear with postauricular swelling and erythema. Given clinical concerns, urgent neuroimaging was arranged. ... Read more >>

Arch Dis Child Educ Pract Ed (Archives of disease in childhood. Education and practice edition)
[2020, :]

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The lipogenic regulator SREBF2 induces Transferrin in circulating melanoma cells and suppresses ferroptosis.

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

Circulating tumor cells (CTCs) are shed by cancer into the bloodstream, where a viable subset overcomes oxidative stress to initiate metastasis. We show that single CTCs from melanoma patients coordinately upregulate lipogenesis and iron homeostasis pathways. These are correlated with both intrinsic and acquired resistance to BRAF inhibitors across clonal ... Read more >>

Cancer Discov (Cancer discovery)
[2020, :]

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NR4A1 suppresses cancer replication stress through R-loop-dependent inhibition of immediate early gene transcriptional elongation

Daniel Haber, Hongshan Guo, Gabriel Golczer, Ben Wittner, Adam Langenbucher, Marcus Zachariah, Taronish Dubash, Xin Hong, Valentine Comaills, Risa Burr, Elad Horwitz, Joanna Vuille, Devon Wiley, Brittany Reeves, Jiamin zhang, Kira Niederhoffer, Chenyue Lu, Benjamin Wesley, Uyen Ho, Mehmet Toner, Lee Zou, Raul Mostoslavsky, Shyamala Maheswaran, Michael Lawrence,

Deregulation of oncogenic proliferative signals triggers replication stress in cancer cells to which they must adapt 1,2 . Immediate early genes (IEGs), identified by their rapid stress-induced transient bursts of expression, are critical to integrating downstream signaling pathways 3,4 . In studying tumor initiation by patient-derived breast cancer cells, we ... Read more >>

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Low cryoprotectant concentration rapid vitrification of mouse oocytes and embryos.

Jie Liu, Gloria Y Lee, John D Biggers, Thomas L Toth, Mehmet Toner,

Vitrification of mammalian oocytes and embryos is typically a two-step procedure involving two solutions of increasing concentrations of cryoprotectants. In the present study, we report a simple vitrification protocol that uses low cryoprotectant concentration and a single medium (LCSM). This medium, along with the traditional high concentration two media (HCTM) ... Read more >>

Cryobiology (Cryobiology)
[2020, :]

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Small and Thin Oral Squamous Cell Carcinomas may Exhibit Adverse Pathologic Prognostic Features.

Mutaz Mohammed Nur, Maimuna Al Saadi, Esther M O'Regan, Maria Van Harten, Mary Toner,

We set out to record the frequency of recognised adverse pathologic features in early oral squamous cell carcinoma (OSCC) and correlate with neck disease, in particular in small and thin carcinomas, a group that might be assumed to behave less aggressively. We also examined the possibility of a biopsy site ... Read more >>

Head Neck Pathol (Head and neck pathology)
[2020, :]

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The detection of oral cancer and potentially malignant disorders in Ireland: An observational study of 100 cases.

John Ahern, Mary Toner, Maria Van Harten, June Nunn,

<h4>Objective</h4>To describe the diagnostic details of a sample of histologically diagnosed malignant and potentially malignant oral lesions from Ireland; to examine how these lesions were first detected, and by whom; and to determine whether factors influenced how these lesions were detected, who detected them, and the type of lesion diagnosed.<h4>Methods</h4>A ... Read more >>

J Public Health Dent (Journal of public health dentistry)
[2020, 80(4):333-337]

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Identification of Somatically Acquired BRCA1/2 Mutations by cfDNA Analysis in Patients with Metastatic Breast Cancer.

Neelima Vidula, Taronish Dubash, Michael S Lawrence, Antoine Simoneau, Andrzej Niemierko, Erica Blouch, Becky Nagy, Whijae Roh, Brian Chirn, Brittany A Reeves, Giuliana Malvarosa, Jochen Lennerz, Steven J Isakoff, Dejan Juric, Douglas Micalizzi, Seth Wander, Laura Spring, Beverly Moy, Kristen Shannon, Jerry Younger, Richard Lanman, Mehmet Toner, A John Iafrate, Gad Getz, Lee Zou, Leif W Ellisen, Shyamala Maheswaran, Daniel A Haber, Aditya Bardia,

<h4>Purpose</h4>Plasma genotyping may identify mutations in potentially "actionable" cancer genes, such as <i>BRCA1/2</i>, but their clinical significance is not well-defined. We evaluated the characteristics of somatically acquired <i>BRCA1/2</i> mutations in patients with metastatic breast cancer (MBC).<h4>Experimental design</h4>Patients with MBC undergoing routine cell-free DNA (cfDNA) next-generation sequencing (73-gene panel) before starting ... Read more >>

Clin Cancer Res (Clinical cancer research : an official journal of the American Association for Cancer Research)
[2020, 26(18):4852-4862]

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Subzero non-frozen preservation of human livers in the supercooled state.

Reinier J de Vries, Shannon N Tessier, Peony D Banik, Sonal Nagpal, Stephanie E J Cronin, Sinan Ozer, Ehab O A Hafiz, Thomas M van Gulik, Martin L Yarmush, James F Markmann, Mehmet Toner, Heidi Yeh, Korkut Uygun,

Preservation of human organs at subzero temperatures has been an elusive goal for decades. The major complication hindering successful subzero preservation is the formation of ice at temperatures below freezing. Supercooling, or subzero non-freezing, preservation completely avoids ice formation at subzero temperatures. We previously showed that rat livers can be ... Read more >>

Nat Protoc (Nature protocols)
[2020, 15(6):2024-2040]

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Immunoassay for HIV Drug Metabolites Tenofovir and Tenofovir Diphosphate.

Derin Sevenler, Ashley Bardon, Marta Fernandez Suarez, Lisa Marshall, Mehmet Toner, Paul K Drain, Rebecca D Sandlin,

Poor patient adherence to antiretroviral medication represents a major obstacle for managing disease and reducing rates of new HIV infections. The measurement of patient drug levels is the most objective method of determining adherence. Tenofovir and tenofovir diphosphate are metabolites of some of the most common HIV medications for treatment ... Read more >>

ACS Infect Dis (ACS infectious diseases)
[2020, 6(7):1635-1642]

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In-flow measurement of cell-cell adhesion using oscillatory inertial microfluidics.

Baris R Mutlu, Taronish Dubash, Claudius Dietsche, Avanish Mishra, Arzu Ozbey, Kevin Keim, Jon F Edd, Daniel A Haber, Shyamala Maheswaran, Mehmet Toner,

Multicellular clusters in circulation can exhibit a substantially different function and biomarker significance compared to individual cells. Notably, clusters of circulating tumor cells (CTCs) are much more effective initiators of metastasis than single CTCs, and correlate with worse patient prognoses. Measuring the cell-cell adhesion strength of CTC clusters is a ... Read more >>

Lab Chip (Lab on a chip)
[2020, 20(9):1612-1620]

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Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.

Richard Y Ebright, Sooncheol Lee, Ben S Wittner, Kira L Niederhoffer, Benjamin T Nicholson, Aditya Bardia, Samuel Truesdell, Devon F Wiley, Benjamin Wesley, Selena Li, Andy Mai, Nicola Aceto, Nicole Vincent-Jordan, Annamaria Szabolcs, Brian Chirn, Johannes Kreuzer, Valentine Comaills, Mark Kalinich, Wilhelm Haas, David T Ting, Mehmet Toner, Shobha Vasudevan, Daniel A Haber, Shyamala Maheswaran, Douglas S Micalizzi,

Circulating tumor cells (CTCs) are shed into the bloodstream from primary tumors, but only a small subset of these cells generates metastases. We conducted an in vivo genome-wide CRISPR activation screen in CTCs from breast cancer patients to identify genes that promote distant metastasis in mice. Genes coding for ribosomal ... Read more >>

Science (Science (New York, N.Y.))
[2020, 367(6485):1468-1473]

Cited: 4 times

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Cell release during perfusion reflects cold ischemic injury in rat livers.

Reinier J de Vries, Casie A Pendexter, Stephanie E J Cronin, Beatriz Marques, Ehab O A Hafiz, Alona Muzikansky, Thomas M van Gulik, James F Markmann, Shannon L Stott, Heidi Yeh, Mehmet Toner, Korkut Uygun, Shannon N Tessier,

The global shortage of donor organs has made it crucial to deeply understand and better predict donor liver viability. However, biomarkers that effectively assess viability of marginal grafts for organ transplantation are currently lacking. Here, we showed that hepatocytes, sinusoidal endothelial, stellate, and liver-specific immune cells were released into perfusates ... Read more >>

Sci Rep (Scientific reports)
[2020, 10(1):1102]

Cited: 2 times

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Microfluidic concentration and separation of circulating tumor cell clusters from large blood volumes.

Jon F Edd, Avanish Mishra, Taronish D Dubash, Stefan Herrera, Ridhwan Mohammad, E Kendall Williams, Xin Hong, Baris R Mutlu, John R Walsh, Fernanda Machado de Carvalho, Berent Aldikacti, Linda T Nieman, Shannon L Stott, Ravi Kapur, Shyamala Maheswaran, Daniel A Haber, Mehmet Toner,

Circulating tumor cells (CTCs) are extremely rare in the blood, yet they account for metastasis. Notably, it was reported that CTC clusters (CTCCs) can be 50-100 times more metastatic than single CTCs, making them particularly salient as a liquid biopsy target. Yet they can split apart and are even rarer, ... Read more >>

Lab Chip (Lab on a chip)
[2020, 20(3):558-567]

Cited: 4 times

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Quantitative Analysis of Circulating Tumor Cells Using RNA-Based Digital Scoring.

Mark Kalinich, Tanya T Kwan, Mehmet Toner, Daniel A Haber, Shyamala Maheswaran,

Circulating tumor cells (CTCs) provide valuable information about the molecular evolution of cancers, as they may initially respond and ultimately progress on therapy. As intact tumor cells isolated from the bloodstream, CTCs also enable assessment of heterogeneous subpopulations, and their analysis may include DNA, RNA, and protein biomarkers. New microfluidic ... Read more >>

Recent Results Cancer Res (Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer)
[2020, 215:77-88]

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Primary and Metastatic Pancreatic Cancer Cells Exhibit Differential Migratory Potentials.

Joo Kyung Park, Thomas Hank, Cally M Scherber, Keith D Lillemoe, Carlos Fernández-Del Castillo, Andrew L Warshaw, Mehmet Toner, Daniel Irimia, Sarah P Thayer, Andrew S Liss,

<h4>Objectives</h4>Pancreatic ductal adenocarcinoma (PDAC) is characterized by early metastatic spread in more than 50% of patients. In this study, we sought to understand the migratory properties of (non)metastatic PDAC cells and determine whether the migration of cancer stem cell (CSC) populations accounts for the aggressive nature of this disease.<h4>Methods</h4>The migratory ... Read more >>

Pancreas (Pancreas)
[2020, 49(1):128-134]

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The Spectrum of Histological Findings in Oral Biopsies

J Ahern, M Toner, E O’ Regan, J Nunn,

Aim: To undertake a retrospective analysis of the use of a diagnostic pathology service, to determine the source of oral biopsies submitted for histological analysis, and to examine the range and frequencies of histologically diagnosed oral lesions in an Irish population. Methods: A retrospective analysis was carried out on all ... Read more >>

Ir Med J (Irish medical journal)
[2019, 112(10):1017]

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Bulk Droplet Vitrification for Primary Hepatocyte Preservation.

Reinier J de Vries, Peony D Banik, Sonal Nagpal, Lindong Weng, Sinan Ozer, Thomas M van Gulik, Mehmet Toner, Shannon N Tessier, Korkut Uygun,

Vitrification is a promising ice-free alternative for classic slow-freezing (at approximately 1 °C/min) cryopreservation of biological samples. Vitrification requires extremely fast cooling rates to achieve transition of water into the glass phase while avoiding injurious ice formation. Although pre-incubation with cryoprotective agents (CPA) can reduce the critical cooling rate of ... Read more >>

J Vis Exp (Journal of visualized experiments : JoVE)
[2019, (152):]

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Leveraging the zebrafish to model organ transplantation.

Luciana Da Silveira Cavalcante, Mehmet Toner, Korkut Uygun, Shannon N Tessier,

PURPOSE OF REVIEW:The availability of organs for transplant fails to meet the demand and this shortage is growing worse every year. As the cost of not getting a suitable donor organ can mean death for patients, new tools and approaches that allows us to make advances in transplantation faster and ... Read more >>

Curr Opin Organ Transplant (Current opinion in organ transplantation)
[2019, 24(5):613-619]

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Supercooling extends preservation time of human livers.

Reinier J de Vries, Shannon N Tessier, Peony D Banik, Sonal Nagpal, Stephanie E J Cronin, Sinan Ozer, Ehab O A Hafiz, Thomas M van Gulik, Martin L Yarmush, James F Markmann, Mehmet Toner, Heidi Yeh, Korkut Uygun,

The inability to preserve vascular organs beyond several hours contributes to the scarcity of organs for transplantation<sup>1,2</sup>. Standard hypothermic preservation at +4 °C (refs. <sup>1,3</sup>) limits liver preservation to less than 12 h. Our group previously showed that supercooled ice-free storage at -6 °C can extend viable preservation of rat livers<sup>4,5</sup> However, scaling ... Read more >>

Nat Biotechnol (Nature biotechnology)
[2019, 37(10):1131-1136]

Cited: 2 times

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A New Test for the Detection of Direct Oral Anticoagulants (Rivaroxaban and Apixaban) in the Emergency Room Setting.

Galit H Frydman, Felix Ellett, Elizabeth M Van Cott, Douglas Hayden, Maulik Majmudar, Charles R Vanderburg, Haley Dalzell, Divya L Padmanabhan, Nick Davis, Julianne Jorgensen, Mehmet Toner, James G Fox, Ronald G Tompkins,

Determining whether a patient has taken a direct oral anticoagulant (DOAC) is critical during the periprocedural and preoperative period in the emergency department. However, the inaccessibility of complete medical records, along with the generally inconsistent sensitivity of conventional coagulation tests to these drugs, complicates clinical decision making and puts patients ... Read more >>

Crit Care Explor (Critical care explorations)
[2019, 1(8):e0024]

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Pathology in Irish medical education.

Hilary Humphreys, Niall Stevens, Desmond Leddin, Grace Callagy, Louise Burke, R William Watson, Mary Toner,

Pathology is the study of disease and is an important component in medical education. However, with medical curriculum reform, its role and contribution to medical courses is under potential threat. We surveyed the status of pathology in all six Irish medical schools. Information was received from five direct undergraduate and ... Read more >>

J Clin Pathol (Journal of clinical pathology)
[2020, 73(1):47-50]

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