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Jared R. Mayers

Samuel K McBrayer, Jared R Mayers, Gabriel J DiNatale, Diana D Shi, Januka Khanal, Abhishek A Chakraborty, Kristopher A Sarosiek, Kimberly J Briggs, Alissa K Robbins, Tomasz Sewastianik, Sarah J Shareef, Benjamin A Olenchock, Seth J Parker, Kensuke Tateishi, Jessica B Spinelli, Mirazul Islam, Marcia C Haigis, Ryan E Looper, Keith L Ligon, Bradley E Bernstein, Ruben D Carrasco, Daniel P Cahill, John M Asara, Christian M Metallo, Neela H Yennawar, Matthew G Vander Heiden, William G Kaelin
IDH1 mutations are common in low-grade gliomas and secondary glioblastomas and cause overproduction of (R)-2HG. (R)-2HG modulates the activity of many enzymes, including some that are linked to transformation and some that are probably bystanders. Although prior work on (R)-2HG targets focused on 2OG-dependent dioxygenases, we found that (R)-2HG potently inhibits the 2OG-dependent transaminases BCAT1 and BCAT2, likely as a bystander effect, thereby decreasing glutamate levels and increasing dependence on glutaminase for the biosynthesis of glutamate and one of its products, glutathione...
September 20, 2018: Cell
Laura V Danai, Ana Babic, Michael H Rosenthal, Emily A Dennstedt, Alexander Muir, Evan C Lien, Jared R Mayers, Karen Tai, Allison N Lau, Paul Jones-Sali, Carla M Prado, Gloria M Petersen, Naoki Takahashi, Motokazu Sugimoto, Jen Jen Yeh, Nicole Lopez, Nabeel Bardeesy, Carlos Fernandez-Del Castillo, Andrew S Liss, Albert C Koong, Justin Bui, Chen Yuan, Marisa W Welch, Lauren K Brais, Matthew H Kulke, Courtney Dennis, Clary B Clish, Brian M Wolpin, Matthew G Vander Heiden
Malignancy is accompanied by changes in the metabolism of both cells and the organism1,2 . Pancreatic ductal adenocarcinoma (PDAC) is associated with wasting of peripheral tissues, a metabolic syndrome that lowers quality of life and has been proposed to decrease survival of patients with cancer3,4 . Tissue wasting is a multifactorial disease and targeting specific circulating factors to reverse this syndrome has been mostly ineffective in the clinic5,6 . Here we show that loss of both adipose and muscle tissue occurs early in the development of pancreatic cancer...
June 2018: Nature
Kyle Zingaro, David Shaw, Jerry Carson, Anke Mayer-Bartschmid, Christian Bender, Christina Alves, Duncan Mcvey, Nan-Xin Qian, Qingxiang Wei, Michael W Laird, Yuan Zhu, Robyn Emmins, John A Follit, Alison Porter, Andrew J Racher, Sarah Milne, Ivan Carubelli, Zhimei Du, Ankita Khatri, Marilyne Failly, Hervé Broly, Frank Lee, Matthew Reeser, Jared Spidel, Karin Anderson, Christine Demaria, Jennifer Di-Carlo, John Gill, Amie Lundquist, Sampath R Kumar, Tony Gill
Monoclonality of mammalian cell lines used for production of biologics is a regulatory expectation and one of the attributes assessed as part of a larger process to ensure consistent quality of the biologic. Historically, monoclonality has been demonstrated through statistics generated from limiting dilution cloning or through verified flow cytometry methods. A variety of new technologies are now on the market with the potential to offer more efficient and robust approaches to generating and documenting a clonal cell line...
July 2018: PDA Journal of Pharmaceutical Science and Technology
Jared R Mayers
No abstract text is available yet for this article.
December 8, 2017: Science
Orianne Olivares, Jared R Mayers, Victoire Gouirand, Margaret E Torrence, Tristan Gicquel, Laurence Borge, Sophie Lac, Julie Roques, Marie-Noëlle Lavaut, Patrice Berthezène, Marion Rubis, Veronique Secq, Stéphane Garcia, Vincent Moutardier, Dominique Lombardo, Juan Lucio Iovanna, Richard Tomasini, Fabienne Guillaumond, Matthew G Vander Heiden, Sophie Vasseur
Tissue architecture contributes to pancreatic ductal adenocarcinoma (PDAC) phenotypes. Cancer cells within PDAC form gland-like structures embedded in a collagen-rich meshwork where nutrients and oxygen are scarce. Altered metabolism is needed for tumour cells to survive in this environment, but the metabolic modifications that allow PDAC cells to endure these conditions are incompletely understood. Here we demonstrate that collagen serves as a proline reservoir for PDAC cells to use as a nutrient source when other fuels are limited...
July 7, 2017: Nature Communications
Jared R Mayers, Matthew G Vander Heiden
Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein...
June 15, 2017: Cancer Research
Shawn M Davidson, Oliver Jonas, Mark A Keibler, Han Wei Hou, Alba Luengo, Jared R Mayers, Jeffrey Wyckoff, Amanda M Del Rosario, Matthew Whitman, Christopher R Chin, Kendall J Condon, Alex Lammers, Katherine A Kellersberger, Brian K Stall, Gregory Stephanopoulos, Dafna Bar-Sagi, Jongyoon Han, Joshua D Rabinowitz, Michael J Cima, Robert Langer, Matthew G Vander Heiden
Mammalian tissues rely on a variety of nutrients to support their physiological functions. It is known that altered metabolism is involved in the pathogenesis of cancer, but which nutrients support the inappropriate growth of intact malignant tumors is incompletely understood. Amino acids are essential nutrients for many cancer cells that can be obtained through the scavenging and catabolism of extracellular protein via macropinocytosis. In particular, macropinocytosis can be a nutrient source for pancreatic cancer cells, but it is not fully understood how the tumor environment influences metabolic phenotypes and whether macropinocytosis supports the maintenance of amino acid levels within pancreatic tumors...
February 2017: Nature Medicine
Erik C Yusko, Brandon R Bruhn, Olivia M Eggenberger, Jared Houghtaling, Ryan C Rollings, Nathan C Walsh, Santoshi Nandivada, Mariya Pindrus, Adam R Hall, David Sept, Jiali Li, Devendra S Kalonia, Michael Mayer
Established methods for characterizing proteins typically require physical or chemical modification steps or cannot be used to examine individual molecules in solution. Ionic current measurements through electrolyte-filled nanopores can characterize single native proteins in an aqueous environment, but currently offer only limited capabilities. Here we show that the zeptolitre sensing volume of bilayer-coated solid-state nanopores can be used to determine the approximate shape, volume, charge, rotational diffusion coefficient and dipole moment of individual proteins...
May 2017: Nature Nanotechnology
Jonathan M Eby, Levi Barse, Steven W Henning, Martijn J W E Rabelink, Jared Klarquist, Emily R Gilbert, Adam M Hammer, Manuel F Fernandez, Nathan Yung, Safia Khan, Hannah G Miller, Edward R Kessler, Elizabeth Garrett-Mayer, Daniel F Dilling, Rob C Hoeben, I Caroline Le Poole
An immunotherapeutic strategy is discussed supporting anti-tumor activity toward malignancies overexpressing ganglioside D3. GD3 can be targeted by NKT cells when derived moieties are presented in the context of CD1d. NKT cells can support anti-tumor responses by secreting inflammatory cytokines and through cytotoxicity toward CD1d+ GD3+ tumors. To overexpress GD3, we generated expression vector DNA and an adenoviral vector encoding the enzyme responsible for generating GD3 from its ubiquitous precursor GM3...
January 2017: Cancer Immunology, Immunotherapy: CII
Jared R Mayers, Margaret E Torrence, Laura V Danai, Thales Papagiannakopoulos, Shawn M Davidson, Matthew R Bauer, Allison N Lau, Brian W Ji, Purushottam D Dixit, Aaron M Hosios, Alexander Muir, Christopher R Chin, Elizaveta Freinkman, Tyler Jacks, Brian M Wolpin, Dennis Vitkup, Matthew G Vander Heiden
Tumor genetics guides patient selection for many new therapies, and cell culture studies have demonstrated that specific mutations can promote metabolic phenotypes. However, whether tissue context defines cancer dependence on specific metabolic pathways is unknown. Kras activation and Trp53 deletion in the pancreas or the lung result in pancreatic ductal adenocarinoma (PDAC) or non-small cell lung carcinoma (NSCLC), respectively, but despite the same initiating events, these tumors use branched-chain amino acids (BCAAs) differently...
September 9, 2016: Science
Terence Verla, Jared S Fridley, Abdul Basit Khan, Rory R Mayer, Ibrahim Omeis
BACKGROUND: Intramedullary spinal cord tumors (IMSCT) account for about 2%-4% of tumors of the central nervous system. Surgical resection continues to be the most effective treatment modality for most intramedullary tumors, with gross total resection leading to preserved neurologic function and improved survival. However, surgical treatment is often difficult and carries significant risk of postoperative neurologic complications. Intraoperative neuromonitoring has been shown to be of clinical importance in the surgical resection of IMSCT...
November 2016: World Neurosurgery
Nirav S Shah, Jared A Greenberg, Moira C McNulty, Kevin S Gregg, James Riddell, Julie E Mangino, Devin M Weber, Courtney L Hebert, Natalie S Marzec, Michelle A Barron, Fredy Chaparro-Rojas, Alejandro Restrepo, Vagish Hemmige, Kunatum Prasidthrathsint, Sandra Cobb, Loreen Herwaldt, Vanessa Raabe, Christopher R Cannavino, Andrea Green Hines, Sara H Bares, Philip B Antiporta, Tonya Scardina, Ursula Patel, Gail Reid, Parvin Mohazabnia, Suresh Kachhdiya, Binh-Minh Le, Connie J Park, Belinda Ostrowsky, Ari Robicsek, Becky A Smith, Jeanmarie Schied, Micah M Bhatti, Stockton Mayer, Monica Sikka, Ivette Murphy-Aguilu, Priti Patwari, Shira R Abeles, Francesca J Torriani, Zainab Abbas, Sophie Toya, Katherine Doktor, Anindita Chakrabarti, Susanne Doblecki-Lewis, David J Looney, Michael Z David
BACKGROUND: Influenza acts synergistically with bacterial co-pathogens. Few studies have described co-infection in a large cohort with severe influenza infection. OBJECTIVES: To describe the spectrum and clinical impact of co-infections. STUDY DESIGN: Retrospective cohort study of patients with severe influenza infection from September 2013 through April 2014 in intensive care units at 33 U.S. hospitals comparing characteristics of cases with and without co-infection in bivariable and multivariable analysis...
July 2016: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
Chen Yuan, Clary B Clish, Chen Wu, Jared R Mayers, Peter Kraft, Mary K Townsend, Mingfeng Zhang, Shelley S Tworoger, Ying Bao, Zhi Rong Qian, Douglas A Rubinson, Kimmie Ng, Edward L Giovannucci, Shuji Ogino, Meir J Stampfer, John Michael Gaziano, Jing Ma, Howard D Sesso, Garnet L Anderson, Barbara B Cochrane, JoAnn E Manson, Margaret E Torrence, Alec C Kimmelman, Laufey T Amundadottir, Matthew G Vander Heiden, Charles S Fuchs, Brian M Wolpin
BACKGROUND: Pancreatic tumors cause changes in whole-body metabolism, but whether prediagnostic circulating metabolites predict survival is unknown. METHODS: We measured 82 metabolites by liquid chromatography-mass spectrometry in prediagnostic plasma from 484 pancreatic cancer case patients enrolled in four prospective cohort studies. Association of metabolites with survival was evaluated using Cox proportional hazards models adjusted for age, cohort, race/ethnicity, cancer stage, fasting time, and diagnosis year...
June 2016: Journal of the National Cancer Institute
Nirav S Shah, Jared A Greenberg, Moira C McNulty, Kevin S Gregg, James Riddell, Julie E Mangino, Devin M Weber, Courtney L Hebert, Natalie S Marzec, Michelle A Barron, Fredy Chaparro-Rojas, Alejandro Restrepo, Vagish Hemmige, Kunatum Prasidthrathsint, Sandra Cobb, Loreen Herwaldt, Vanessa Raabe, Christopher R Cannavino, Andrea Green Hines, Sara H Bares, Philip B Antiporta, Tonya Scardina, Ursula Patel, Gail Reid, Parvin Mohazabnia, Suresh Kachhdiya, Binh-Minh Le, Connie J Park, Belinda Ostrowsky, Ari Robicsek, Becky A Smith, Jeanmarie Schied, Micah M Bhatti, Stockton Mayer, Monica Sikka, Ivette Murphy-Aguilu, Priti Patwari, Shira R Abeles, Francesca J Torriani, Zainab Abbas, Sophie Toya, Katherine Doktor, Anindita Chakrabarti, Susanne Doblecki-Lewis, David J Looney, Michael Z David
BACKGROUND: Influenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013-2014 influenza season. Little is known about the epidemiology of severe influenza during this season. METHODS: A retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes...
November 2015: Infection Control and Hospital Epidemiology
Xi-Nian Zuo, Jeffrey S Anderson, Pierre Bellec, Rasmus M Birn, Bharat B Biswal, Janusch Blautzik, John C S Breitner, Randy L Buckner, Vince D Calhoun, F Xavier Castellanos, Antao Chen, Bing Chen, Jiangtao Chen, Xu Chen, Stanley J Colcombe, William Courtney, R Cameron Craddock, Adriana Di Martino, Hao-Ming Dong, Xiaolan Fu, Qiyong Gong, Krzysztof J Gorgolewski, Ying Han, Ye He, Yong He, Erica Ho, Avram Holmes, Xiao-Hui Hou, Jeremy Huckins, Tianzi Jiang, Yi Jiang, William Kelley, Clare Kelly, Margaret King, Stephen M LaConte, Janet E Lainhart, Xu Lei, Hui-Jie Li, Kaiming Li, Kuncheng Li, Qixiang Lin, Dongqiang Liu, Jia Liu, Xun Liu, Yijun Liu, Guangming Lu, Jie Lu, Beatriz Luna, Jing Luo, Daniel Lurie, Ying Mao, Daniel S Margulies, Andrew R Mayer, Thomas Meindl, Mary E Meyerand, Weizhi Nan, Jared A Nielsen, David O'Connor, David Paulsen, Vivek Prabhakaran, Zhigang Qi, Jiang Qiu, Chunhong Shao, Zarrar Shehzad, Weijun Tang, Arno Villringer, Huiling Wang, Kai Wang, Dongtao Wei, Gao-Xia Wei, Xu-Chu Weng, Xuehai Wu, Ting Xu, Ning Yang, Zhi Yang, Yu-Feng Zang, Lei Zhang, Qinglin Zhang, Zhe Zhang, Zhiqiang Zhang, Ke Zhao, Zonglei Zhen, Yuan Zhou, Xing-Ting Zhu, Michael P Milham
Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics...
2014: Scientific Data
Jared R Mayers, Matthew G Vander Heiden
To fuel unregulated proliferation, cancer cells alter metabolism to support macromolecule biosynthesis. Cell culture studies have revealed how different oncogenic mutations and nutrients impact metabolism. Glucose and glutamine are the primary fuels used in vitro; however, recent studies have suggested that utilization of other amino acids as well as lipids and protein can also be important to cancer cells. Early investigations of tumor metabolism are translating these findings to the biology of whole tumors and suggest that additional complexity exists beyond nutrient availability alone in vivo...
March 2015: Trends in Biochemical Sciences
Jared R Mayers, Chen Wu, Clary B Clish, Peter Kraft, Margaret E Torrence, Brian P Fiske, Chen Yuan, Ying Bao, Mary K Townsend, Shelley S Tworoger, Shawn M Davidson, Thales Papagiannakopoulos, Annan Yang, Talya L Dayton, Shuji Ogino, Meir J Stampfer, Edward L Giovannucci, Zhi Rong Qian, Douglas A Rubinson, Jing Ma, Howard D Sesso, John Michael Gaziano, Barbara B Cochrane, Simin Liu, Jean Wactawski-Wende, JoAnn E Manson, Michael N Pollak, Alec C Kimmelman, Amanda Souza, Kerry Pierce, Thomas J Wang, Robert E Gerszten, Charles S Fuchs, Matthew G Vander Heiden, Brian M Wolpin
Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and survive less than 12 months. PDAC has been linked with obesity and glucose intolerance, but whether changes in circulating metabolites are associated with early cancer progression is unknown. To better understand metabolic derangements associated with early disease, we profiled metabolites in prediagnostic plasma from individuals with pancreatic cancer (cases) and matched controls from four prospective cohort studies...
October 2014: Nature Medicine
Sarah-Maria Fendt, Eric L Bell, Mark A Keibler, Benjamin A Olenchock, Jared R Mayers, Thomas M Wasylenko, Natalie I Vokes, Leonard Guarente, Matthew G Vander Heiden, Gregory Stephanopoulos
Reductively metabolized glutamine is a major cellular carbon source for fatty acid synthesis during hypoxia or when mitochondrial respiration is impaired. Yet, a mechanistic understanding of what determines reductive metabolism is missing. Here we identify several cellular conditions where the α-ketoglutarate/citrate ratio is changed due to an altered acetyl-CoA to citrate conversion, and demonstrate that reductive glutamine metabolism is initiated in response to perturbations that result in an increase in the α-ketoglutarate/citrate ratio...
2013: Nature Communications
Jared R Mayers, Matthew G Vander Heiden
No abstract text is available yet for this article.
July 2013: Nature Medicine
Justin R Boike, Jared S Bortman, Jonathan M Radosta, Crescent L Turner, Lisa Anderson-Shaw, Nikki M Centomani, William H Chamberlin, David Mayer, Timothy McDonald, Jay L Goldstein
BACKGROUND: Internal Medicine resident (IMR) physician reporting of patient safety events (PSEs) is suboptimal and may be related to poor attitudes toward reporting. PURPOSE: The objective was to evaluate the impact of a PSE reporting expectation on the rates of reporting among IMRs. METHODS: In this prospective cohort study, IMRs were informed of an expectation to submit 1 or more PSE report per month based on the ACGME core competencies...
June 2013: Journal of Patient Safety
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