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Tony Hunter

Cynthia L Hsu, Elian X Lee, Kara L Gordon, Edwin A Paz, Wen-Chuan Shen, Kohta Ohnishi, Jill Meisenhelder, Tony Hunter, Albert R La Spada
Autophagy is the major cellular pathway by which macromolecules are degraded, and amino acid depletion powerfully activates autophagy. MAP4K3, or germinal-center kinase-like kinase, is required for robust cell growth in response to amino acids, but the basis for MAP4K3 regulation of cellular metabolic disposition remains unknown. Here we identify MAP4K3 as an amino acid-dependent regulator of autophagy through its phosphorylation of transcription factor EB (TFEB), a transcriptional activator of autophagy, and through amino acid starvation-dependent lysosomal localization of MAP4K3...
March 5, 2018: Nature Communications
Jiaji G Chen, Xia Liu, Manit Munshi, Lian Xu, Nicholas Tsakmaklis, Maria G Demos, Amanda Kofides, Maria Luisa Guerrera, Gloria G Chan, Christopher J Patterson, Kirsten E Meid, Joshua Gustine, Toni Dubeau, Patricia Severns, Jorge J Castillo, Zachary R Hunter, Jinhua Wang, Sara J Buhrlage, Nathanael S Gray, Steven P Treon, Guang Yang
Acquired ibrutinib resistance due to BTKCys481 mutations occurs in B-cell malignancies, including those with MYD88 mutations. BTKCys481 mutations are usually sub-clonal, and their relevance to clinical progression remains unclear. Moreover, the signaling pathways that promote ibrutinib resistance remain to be clarified. We therefore engineered BTKCys481Ser and BTKWT expressing MYD88 mutated WM and ABC DLBCL cells, and observed re-activation of BTK-PLCγ2-ERK1/2 signaling in the presence of ibrutinib in only the former...
March 1, 2018: Blood
Jorge J Castillo, Joshua N Gustine, Kirsten Meid, Toni E Dubeau, Patricia Severns, Lian Xu, Guang Yang, Zachary R Hunter, Steven P Treon
Waldenström macroglobulinaemia (WM) is a rare and incurable lymphoma. Comparative studies evaluating the efficacy of primary therapy in symptomatic WM patients have not been performed. In this study, we compared response and survival outcomes in WM patients who received primary therapy with cyclophosphamide-dexamethasone-rituximab (CDR), bortezomib-dexamethasone-rituximab (BDR) and bendamustine-rituximab (Benda-R), as well as maintenance rituximab following primary therapy. Analyses were adjusted for relevant clinical factors associated with response and survival...
February 22, 2018: British Journal of Haematology
Zhimin Lu, Tony Hunter
Protein kinases regulate every aspect of cellular activity, whereas metabolic enzymes are responsible for energy production and catabolic and anabolic processes. Emerging evidence demonstrates that some metabolic enzymes, such as pyruvate kinase M2 (PKM2), phosphoglycerate kinase 1 (PGK1), ketohexokinase (KHK) isoform A (KHK-A), hexokinase (HK), and nucleoside diphosphate kinase 1 and 2 (NME1/2), that phosphorylate soluble metabolites can also function as protein kinases and phosphorylate a variety of protein substrates to regulate the Warburg effect, gene expression, cell cycle progression and proliferation, apoptosis, autophagy, exosome secretion, T cell activation, iron transport, ion channel opening, and many other fundamental cellular functions...
February 17, 2018: Trends in Biochemical Sciences
Liz Glidewell, Thomas A Willis, Duncan Petty, Rebecca Lawton, Rosemary R C McEachan, Emma Ingleson, Peter Heudtlass, Andrew Davies, Tony Jamieson, Cheryl Hunter, Suzanne Hartley, Kara Gray-Burrows, Susan Clamp, Paul Carder, Sarah Alderson, Amanda J Farrin, Robbie Foy
BACKGROUND: Interpreting evaluations of complex interventions can be difficult without sufficient description of key intervention content. We aimed to develop an implementation package for primary care which could be delivered using typically available resources and could be adapted to target determinants of behaviour for each of four quality indicators: diabetes control, blood pressure control, anticoagulation for atrial fibrillation and risky prescribing. We describe the development and prospective verification of behaviour change techniques (BCTs) embedded within the adaptable implementation packages...
February 17, 2018: Implementation Science: IS
Jeffrey Settleman, Charles L Sawyers, Tony Hunter
More than 30 published articles have suggested that a protein kinase called MELK is an attractive therapeutic target in human cancer, but three recent reports describe compelling evidence that it is not. These reports highlight the caveats associated with some of the research tools that are commonly used to validate candidate therapeutic targets in cancer research.
February 8, 2018: ELife
Yusheng Bian, Feng Guo, Shujie Yang, Zhangming Mao, Hunter Bachman, Shi-Yang Tang, Liqiang Ren, Bin Zhang, Jianying Gong, Xiasheng Guo, Tony Jun Huang
The precise manipulation of acoustic fields in microfluidics is of critical importance for the realization of many biomedical applications. Despite the tremendous efforts devoted to the field of acoustofluidics during recent years, dexterous control, with an arbitrary and complex acoustic wavefront, in a prescribed, microscale region is still out of reach. Here, we introduce the concept of acoustofluidic waveguide, a three-dimensional compact configuration that is capable of locally guiding acoustic waves into a fluidic environment...
August 2017: Microfluidics and Nanofluidics
Hunter Bachman, Po-Hsun Huang, Shuaiguo Zhao, Shujie Yang, Peiran Zhang, Hai Fu, Tony Jun Huang
Acoustofluidic devices have continuously demonstrated their potential to impact medical diagnostics and lab-on-a-chip applications. To bring these technologies to real-world applications, they must be made more accessible to end users. Herein, we report on the effort to provide an easy-to-use and portable system for controlling sharp-edge-based acoustofluidic devices. With the use of a cell phone and a modified Bluetooth® speaker, on-demand and hands-free pumping and mixing are achieved. Additionally, a novel design for a sharp-edge-based acoustofluidic device is proposed that combines both pumping and mixing functions into a single device, thus removing the need for external equipment typically needed to accomplish these two tasks...
January 5, 2018: Lab on a Chip
Joshua N Gustine, Kirsten Meid, Toni Dubeau, Patricia Severns, Zachary R Hunter, Yang Guang, Lian Xu, Steven P Treon, Jorge J Castillo
Ibrutinib is the first approved therapy for symptomatic patients with Waldenström macroglobulinemia (WM). The reasons for discontinuing ibrutinib and subsequent outcomes have not been previously evaluated in WM patients. We therefore conducted a retrospective review of 189 WM patients seen at our institution who received treatment with ibrutinib, of whom 51 (27%) have discontinued therapy. Reasons for discontinuation include: disease progression (n=27; 14%), toxicity (n=15; 8%), non-response (n=5; 3%), and other unrelated reasons (n=4; 2%)...
December 27, 2017: American Journal of Hematology
Carolyn Sipes, Kathleen Hunter, Dee McGonigle, Karen West, Taryn Hill, Toni Hebda
Information technology use in healthcare delivery mandates a prepared workforce. The initial Health Information Technology Competencies tool resulted from a 2-year transatlantic effort by experts from the US and European Union to identify approaches to develop skills and knowledge needed by healthcare workers. It was determined that competencies must be identified before strategies are established, resulting in a searchable database of more than 1000 competencies representing five domains, five skill levels, and more than 250 roles...
December 2017: Computers, Informatics, Nursing: CIN
Yi Ma, Gregory Jones, Yeng Kwang Tay, Toni Hunter, Dane Holden, Stephen Rodgers-Wilson, Paul Cashin, Pee Yau Tan, Daniel Croagh
INTRODUCTION: Studies have shown that post-operative telephone follow-up is satisfactory and effective. As high quality evidence is scant, we conducted a randomized controlled trial to compare it against outpatient clinic review for emergency laparoscopic appendicectomy or cholecystectomy. METHOD: Patients who received emergency laparoscopic appendicectomy or cholecystectomy were eligible for this study. Once recruited, they were randomly allocated to either clinic review or telephone follow-up on discharge...
December 5, 2017: ANZ Journal of Surgery
Steven P Treon, Joshua Gustine, Lian Xu, Robert J Manning, Nicholas Tsakmaklis, Maria Demos, Kirsten Meid, Maria L Guerrera, Manit Munshi, Gloria Chan, Jiaji Chen, Amanda Kofides, Christopher J Patterson, Guang Yang, Xia Liu, Patricia Severns, Toni Dubeau, Zachary R Hunter, Jorge J Castillo
MYD88 mutations are present in 95% of Waldenstrom Macroglobulinaemia (WM) patients, and support diagnostic discrimination from other IgM-secreting B-cell malignancies. Diagnostic discrimination can be difficult among suspected wild-type MYD88 (MYD88WT ) WM cases. We systematically reviewed the clinical, pathological and laboratory studies for 64 suspected MYD88WT WM patients. World Health Organization and WM consensus guidelines were used to establish clinicopathological diagnosis. Up to 30% of suspected MYD88WT WM cases had an alternative clinicopathological diagnosis, including IgM multiple myeloma...
February 2018: British Journal of Haematology
Arshad Khan, Lovepreet Mann, Ramesha Papanna, Mi-Ae Lyu, Christopher R Singh, Scott Olson, N Tony Eissa, Jeffrey Cirillo, Gobardhan Das, Robert L Hunter, Chinnaswamy Jagannath
Human mesenchymal stem cells (MSCs) express scavenger receptors that internalize lipids, including oxidized low-density lipoprotein (oxLDL). We report that MSCs phagocytose Mycobacterium tuberculosis (Mtb) through two types of scavenger receptors (SRs; MARCO and SR-B1), as blockade of the receptors with antibodies or siRNA knockdown decreased the uptake of Mtb. MSCs also expressed mannose receptor (MR) that was found to endocytose rhodamine-labeled mannosylated BSA (rMBSA), though the receptor was not involved in the uptake of Mtb...
November 8, 2017: Scientific Reports
Mengxi Wu, Zhangming Mao, Kejie Chen, Hunter Bachman, Yuchao Chen, Joseph Rufo, Liqiang Ren, Peng Li, Lin Wang, Tony Jun Huang
The separation of nanoscale particles based on their differences in size is an essential technique to the nanoscience and nanotechnology community. Here, nanoparticles are successfully separated in a continuous flow by using tilted-angle standing surface acoustic waves. The acoustic field deflects nanoparticles based on volume, and the fractionation of nanoparticles is optimized by tuning the cutoff parameters. The continuous separation of nanoparticlesis demonstrated with a ≈90% recovery rate. The acoustic nanoparticle separation method is versatile, non-invasive, and simple...
April 11, 2017: Advanced Functional Materials
Kevin Adam, Tony Hunter
Protein phosphorylation is the most common type of post-translational modification in eukaryotes. The phosphoproteome is defined as the complete set of experimentally detectable phosphorylation sites present in a cell's proteome under various conditions. However, we are still far from identifying all the phosphorylation sites in a cell mainly due to the lack of information about phosphorylation events involving residues other than Ser, Thr and Tyr. Four types of phosphate-protein linkage exist and these generate nine different phosphoresidues-pSer, pThr, pTyr, pHis, pLys, pArg, pAsp, pGlu and pCys...
October 23, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
Sharad C Paudyal, Shan Li, Hong Yan, Tony Hunter, Zhongsheng You
Nucleolytic resection of DNA double-strand breaks (DSBs) is essential for both checkpoint activation and homology-mediated repair; however, the precise mechanism of resection, especially the initiation step, remains incompletely understood. Resection of blocked ends with protein or chemical adducts is believed to be initiated by the MRN complex in conjunction with CtIP through internal cleavage of the 5' strand DNA. However, it is not clear whether resection of clean DSBs with free ends is also initiated by the same mechanism...
November 16, 2017: Nucleic Acids Research
Daniel Matthiä, Donald M Hassler, Wouter de Wet, Bent Ehresmann, Ana Firan, John Flores-McLaughlin, Jingnan Guo, Lawrence H Heilbronn, Kerry Lee, Hunter Ratliff, Ryan R Rios, Tony C Slaba, Michael Smith, Nicholas N Stoffle, Lawrence W Townsend, Thomas Berger, Günther Reitz, Robert F Wimmer-Schweingruber, Cary Zeitlin
The radiation environment at the Martian surface is, apart from occasional solar energetic particle events, dominated by galactic cosmic radiation, secondary particles produced in their interaction with the Martian atmosphere and albedo particles from the Martian regolith. The highly energetic primary cosmic radiation consists mainly of fully ionized nuclei creating a complex radiation field at the Martian surface. This complex field, its formation and its potential health risk posed to astronauts on future manned missions to Mars can only be fully understood using a combination of measurements and model calculations...
August 2017: Life Sciences in Space Research
Sixing Li, Fen Ma, Hunter Bachman, Craig E Cameron, Xiangqun Zeng, Tony Jun Huang
Bacterial separation from human blood samples can help with the identification of pathogenic bacteria for sepsis diagnosis. In this work, we report an acoustofluidic device for label-free bacterial separation from human blood samples. In particular, we exploit the acoustic radiation force generated from a tilted-angle standing surface acoustic wave (taSSAW) field to separate E. coli from human blood cells based on their size difference. Flow cytometry analysis of the E. coli separated from red blood cells (RBCs) shows a purity of more than 96%...
January 1, 2017: Journal of Micromechanics and Microengineering: Structures, Devices, and Systems
Thom Dallimore, Tony Hunter, Jolyon M Medlock, Alexander G C Vaux, Ralph E Harbach, Clare Strode
BACKGROUND: The mosquito Aedes aegypti (L.) is found in tropical and sub-tropical regions where it is the major vector of dengue fever, yellow fever, chikungunya and more recently Zika virus. Given its importance as a vector of arboviruses and its propensity to be transported to new regions, the European Centre for Disease Prevention and Control (ECDC) has placed Ae. aegypti on a list of potentially invasive mosquito species. It was previously reported in the United Kingdom (UK) in 1865 and 1919 but did not establish on either occasion...
June 24, 2017: Parasites & Vectors
Prashant Nair
No abstract text is available yet for this article.
June 27, 2017: Proceedings of the National Academy of Sciences of the United States of America
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