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Robert Langer

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https://www.readbyqxmd.com/read/28696296/multiplexed-rnai-therapy-against-brain-tumor-initiating-cells-via-lipopolymeric-nanoparticle-infusion-delays-glioblastoma-progression
#1
Dou Yu, Omar F Khan, Mario L Suvà, Biqin Dong, Wojciech K Panek, Ting Xiao, Meijing Wu, Yu Han, Atique U Ahmed, Irina V Balyasnikova, Hao F Zhang, Cheng Sun, Robert Langer, Daniel G Anderson, Maciej S Lesniak
Brain tumor-initiating cells (BTICs) have been identified as key contributors to therapy resistance, recurrence, and progression of diffuse gliomas, particularly glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the blood-brain barrier, underscoring the urgent need to develop novel therapeutic strategies. Additionally, intratumoral heterogeneity and adaptations to therapeutic pressure by BTICs impede the discovery of effective anti-BTIC therapies and limit the efficacy of individual gene targeting...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28691930/ly6clo-monocytes-drive-immunosuppression-and-confer-resistance-to-anti-vegfr2-cancer-therapy
#2
Keehoon Jung, Takahiro Heishi, Omar F Khan, Piotr S Kowalski, Joao Incio, Nuh N Rahbari, Euiheon Chung, Jeffrey W Clark, Christopher G Willett, Andrew D Luster, Seok Hyun Yun, Robert Langer, Daniel G Anderson, Timothy P Padera, Rakesh K Jain, Dai Fukumura
Current anti-VEGF therapies for colorectal cancer (CRC) provide limited survival benefit, as tumors rapidly develop resistance to these agents. Here, we have uncovered an immunosuppressive role for nonclassical Ly6Clo monocytes that mediates resistance to anti-VEGFR2 treatment. We found that the chemokine CX3CL1 was upregulated in both human and murine tumors following VEGF signaling blockade, resulting in recruitment of CX3CR1+Ly6Clo monocytes into the tumor. We also found that treatment with VEGFA reduced expression of CX3CL1 in endothelial cells in vitro...
July 10, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28681930/synthesis-and-biological-evaluation-of-ionizable-lipid-materials-for-the-in-vivo-delivery-of-messenger-rna-to-b-lymphocytes
#3
Owen S Fenton, Kevin J Kauffman, James C Kaczmarek, Rebecca L McClellan, Siddharth Jhunjhunwala, Mark W Tibbitt, Manhao D Zeng, Eric A Appel, Joseph R Dorkin, Faryal F Mir, Jung H Yang, Matthias A Oberli, Michael W Heartlein, Frank DeRosa, Robert Langer, Daniel G Anderson
B lymphocytes regulate several aspects of immunity including antibody production, cytokine secretion, and T-cell activation; moreover, B cell misregulation is implicated in autoimmune disorders and cancers such as multiple sclerosis and non-Hodgkin's lymphomas. The delivery of messenger RNA (mRNA) into B cells can be used to modulate and study these biological functions by means of inducing functional protein expression in a dose-dependent and time-controlled manner. However, current in vivo mRNA delivery systems fail to transfect B lymphocytes and instead primarily target hepatocytes and dendritic cells...
July 6, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28641400/cytosolic-delivery-of-sirna-by-ultra-high-affinity-dsrna-binding-proteins
#4
Nicole J Yang, Monique J Kauke, Fangdi Sun, Lucy F Yang, Katie F Maass, Michael W Traxlmayr, Yao Yu, Yingda Xu, Robert S Langer, Daniel G Anderson, K Dane Wittrup
Protein-based methods of siRNA delivery are capable of uniquely specific targeting, but are limited by technical challenges such as low potency or poor biophysical properties. Here, we engineered a series of ultra-high affinity siRNA binders based on the viral protein p19 and developed them into siRNA carriers targeted to the epidermal growth factor receptor (EGFR). Combined in trans with a previously described endosome-disrupting agent composed of the pore-forming protein Perfringolysin O (PFO), potent silencing was achieved in vitro with no detectable cytotoxicity...
June 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28625520/immunogenicity-of-pulsatile-release-plga-microspheres-for-single-injection-vaccination
#5
Rohiverth Guarecuco, Jennifer Lu, Kevin J McHugh, James J Norman, Lavanya S Thapa, Emily Lydon, Robert Langer, Ana Jaklenec
The World Health Organization's Expanded Programme on Immunization has led to a dramatic rise in worldwide vaccination rates over the past 40years, yet 19.4 million infants remain underimmunized each year. Many of these infants have received at least one vaccine dose but may remain unprotected because they did not receive subsequent booster doses due to logistical challenges. This study aimed to develop injectable controlled release microparticles with kinetics that mimic common vaccine dosing regimens consisting of large antigen doses administered periodically over the course of months in order to eliminate the need for boosters...
June 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28591112/the-promise-of-organ-and-tissue-preservation-to-transform-medicine
#6
Sebastian Giwa, Jedediah K Lewis, Luis Alvarez, Robert Langer, Alvin E Roth, George M Church, James F Markmann, David H Sachs, Anil Chandraker, Jason A Wertheim, Martine Rothblatt, Edward S Boyden, Elling Eidbo, W P Andrew Lee, Bohdan Pomahac, Gerald Brandacher, David M Weinstock, Gloria Elliott, David Nelson, Jason P Acker, Korkut Uygun, Boris Schmalz, Brad P Weegman, Alessandro Tocchio, Greg M Fahy, Kenneth B Storey, Boris Rubinsky, John Bischof, Janet A W Elliott, Teresa K Woodruff, G John Morris, Utkan Demirci, Kelvin G M Brockbank, Erik J Woods, Robert N Ben, John G Baust, Dayong Gao, Barry Fuller, Yoed Rabin, David C Kravitz, Michael J Taylor, Mehmet Toner
The ability to replace organs and tissues on demand could save or improve millions of lives each year globally and create public health benefits on par with curing cancer. Unmet needs for organ and tissue preservation place enormous logistical limitations on transplantation, regenerative medicine, drug discovery, and a variety of rapidly advancing areas spanning biomedicine. A growing coalition of researchers, clinicians, advocacy organizations, academic institutions, and other stakeholders has assembled to address the unmet need for preservation advances, outlining remaining challenges and identifying areas of underinvestment and untapped opportunities...
June 7, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28561737/synergistic-interactions-with-pi3k-inhibition-that-induce-apoptosis
#7
Yaara Zwang, Oliver Jonas, Casandra Chen, Mikael L Rinne, John G Doench, Federica Piccioni, Li Tan, Hai-Tsang Huang, Jinhua Wang, Young Jin Ham, Joyce O'Connell, Patrick Bhola, Mihir Doshi, Matthew Whitman, Michael Cima, Anthony Letai, David E Root, Robert S Langer, Nathanael Gray, William C Hahn
Activating mutations involving the PI3K pathway occur frequently in human cancers. However, PI3K inhibitors primarily induce cell cycle arrest, leaving a significant reservoir of tumor cells that may acquire or exhibit resistance. We searched for genes that are required for the survival of PI3K mutant cancer cells in the presence of PI3K inhibition by conducting a genome scale shRNA-based apoptosis screen in a PIK3CA mutant human breast cancer cell. We identified 5 genes (PIM2, ZAK, TACC1, ZFR, ZNF565) whose suppression induced cell death upon PI3K inhibition...
May 31, 2017: ELife
https://www.readbyqxmd.com/read/28552846/expression-analysis-of-lc3b-and-p62-indicates-intact-activated-autophagy-is-associated-with-an-unfavorable-prognosis-in-colon-cancer
#8
Monique Niklaus, Olivia Adams, Sabina Berezowska, Inti Zlobec, Franziska Graber, Julia Slotta-Huspenina, Ulrich Nitsche, Robert Rosenberg, Mario P Tschan, Rupert Langer
Autophagy is a lysosomal degradation and recycling process implicated in cancer progression and therapy resistance. We assessed the impact of basal autophagy in colon cancer (CC) in vitro and ex vivo. Functional autophagy was demonstrated in CC cell lines (LoVo; HT-29) showing a dose-dependent increase of the autophagy markers LC3B, p62 and autophagic vesciles upon increasing concentrations of the autophagy inhibitor chloroquine, which was demonstrated by immunoblotting, immunofluorescence and electron microscopy...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28516419/abstracts-of-the-52nd-workshop-for-pediatric-research-frankfurt-germany-27-28-october-2016
#9
Rhea van den Bruck, Patrick P Weil, Thomas Ziegenhals, Philipp Schreiner, Stefan Juranek, Daniel Gödde, Silvia Vogel, Frauke Schuster, Valerie Orth, Johannes Dörner, Daniel Pembaur, Meike Röper, Stefan Störkel, Hubert Zirngibl, Stefan Wirth, Andreas C W Jenke, Jan Postberg, Nikolas Boy, Jana Heringer, Gisela Haege, Esther M Glahn, Georg F Hoffmann, Sven F Garbade, Peter Burgard, Stefan Kölker, Cho-Ming Chao, Faady Yahya, Alena Moiseenko, Amit Shrestha, Negah Ahmadvand, Jennifer Quantius, Jochen Wilhelm, Elie El-Agha, Klaus-Peter Zimmer, Saverio Bellusci, Christian Staufner, Stefan Kölker, Holger Prokisch, Georg F Hoffmann, Stephan Seeliger, Matthias Müller, Andreas Hippe, Henrik Steinkraus, Roland Wauer, Burkhard Lachmann, Sigrun R Hofmann, Christian M Hedrich, Jakob Zierk, Farhad Arzideh, Rainer Haeckel, Wolfgang Rascher, Manfred Rauh, Markus Metzler, Sebastian Thieme, Joanna Bandoła, Cornelia Richter, Martin Ryser, Arshad Jamal, Michelle P Ashton, Malte von Bonin, Matthias Kuhn, Christian M Hedrich, Ezio Bonifacio, Reinhard Berner, Sebastian Brenner, Johanna Hammersen, Cristina Has, Nora Naumann-Bartsch, Daniel Stachel, Dimitra Kiritsi, Stephan Söder, Mathilde Tardieu, Markus Metzler, Leena Bruckner-Tuderman, Holm Schneider, F Bohne, D Langer, R Cencic, T Eggermann, U Zechner, J Pelletier, F Zepp, T Enklaar, D Prawitt, Martin Pech, Markus Weckmann, Femke-Anouska Heinsen, Andre Franke, Christine Happle, Anna-Maria Dittrich, Gesine Hansen, Oliver Fuchs, Erika von Mutius, Brian G Oliver, Matthias V Kopp, Claudia Paret, Alexandra Russo, Johanna Theruvath, Bettina Keller, Khalifa El Malki, Nadine Lehmann, Arthur Wingerter, Marie A Neu, Gerhold-Ay Aslihan, Wolfgang Wagner, Clemens Sommer, Torsten Pietsch, Larissa Seidmann, Jörg Faber, Felix Schreiner, Merle Ackermann, Michael Michalik, Eva Rother, Andras Bilkei-Gorzo, Ildiko Racz, Laura Bindila, Beat Lutz, Jörg Dötsch, Andreas Zimmer, Joachim Woelfle, Hendrik S Fischer, Tim L Ullrich, Christoph Bührer, Christoph Czernik, Gerd Schmalisch, Robert Stein, Sigrun R Hofmann, Judith Hagenbuchner, Ursula Kiechl-Kohlendorfer, Petra Obexer, Michael J Ausserlechner, Niki T Loges, Adrien Tobias Frommer, Julia Wallmeier, Heymut Omran, Soner Öner-Sieben, Martina Gimpfl, Jan Rozman, Martin Irmler, Johannes Beckers, Martin Hrabe De Angelis, Adelbert Roscher, Eckhard Wolf, Regina Ensenauer, Karolina Nemes, Michael Frühwald, Martin Hasselblatt, Reiner Siebert, Uwe Kordes, Marcel Kool, Haicui Wang, Holly Hardy, Osama Refai, Katy E S Barwick, Holly H Zimmerman, Joachim Weis, Emma L Baple, Andrew H Crosby, Sebahattin Cirak, C Hellmuth, O Uhl, M Standl, J Heinrich, E Thiering, B Koletzko, Lena Blümel, Kornelius Kerl, Daniel Picard, Michael C Frühwald, Max C Liebau, Guido Reifenberger, Arndt Borkhardt, Martin Hasselblatt, Marc Remke, D Tews, M Wabitsch, P Fischer-Posovszky, Mike-Andrew Westhoff, Lisa Nonnenmacher, Julia Langhans, Lukas Schneele, Nancy Trenkler, Klaus-Michael Debatin
No abstract text is available yet for this article.
May 2017: Molecular and Cellular Pediatrics
https://www.readbyqxmd.com/read/28512291/characterization-of-mechanically-matched-hydrogel-coatings-to-improve-the-biocompatibility-of-neural-implants
#10
Kevin C Spencer, Jay C Sy, Khalil B Ramadi, Ann M Graybiel, Robert Langer, Michael J Cima
Glial scar is a significant barrier to neural implant function. Micromotion between the implant and tissue is suspected to be a key driver of glial scar formation around neural implants. This study explores the ability of soft hydrogel coatings to modulate glial scar formation by reducing local strain. PEG hydrogels with controllable thickness and elastic moduli were formed on the surface of neural probes. These coatings significantly reduced the local strain resulting from micromotion around the implants. Coated implants were found to significantly reduce scarring in vivo, compared to hard implants of identical diameter...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28493672/correction-to-living-biomaterials
#11
Mark W Tibbitt, Robert Langer
No abstract text is available yet for this article.
May 11, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28487915/donor-ligands-based-on-tricoordinate-boron-formed-by-b-h-activation-of-bis-phosphine-boronium-salts
#12
Maik Grätz, Andreas Bäcker, Lisa Vondung, Leon Maser, Arian Reincke, Robert Langer
We report a novel method for the preparation of PBP-pincer complexes from bis(phosphine)boronium salts. The central (R3P)2HB-moiety in a palladium complex is demonstrated to be a L-type ligand, therewith completing a series of pincer-type complexes with Z-, X- and L-type boron-based ligands, respectively.
June 29, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28459449/in-vivo-genome-editing-and-organoid-transplantation-models-of-colorectal-cancer-and-metastasis
#13
Jatin Roper, Tuomas Tammela, Naniye Malli Cetinbas, Adam Akkad, Ali Roghanian, Steffen Rickelt, Mohammad Almeqdadi, Katherine Wu, Matthias A Oberli, Francisco Sánchez-Rivera, Yoona K Park, Xu Liang, George Eng, Martin S Taylor, Roxana Azimi, Dmitriy Kedrin, Rachit Neupane, Semir Beyaz, Ewa T Sicinska, Yvelisse Suarez, James Yoo, Lillian Chen, Lawrence Zukerberg, Pekka Katajisto, Vikram Deshpande, Adam J Bass, Philip N Tsichlis, Jacqueline Lees, Robert Langer, Richard O Hynes, Jianzhu Chen, Arjun Bhutkar, Tyler Jacks, Ömer H Yilmaz
In vivo interrogation of the function of genes implicated in tumorigenesis is limited by the need to generate and cross germline mutant mice. Here we describe approaches to model colorectal cancer (CRC) and metastasis, which rely on in situ gene editing and orthotopic organoid transplantation in mice without cancer-predisposing mutations. Autochthonous tumor formation is induced by CRISPR-Cas9-based editing of the Apc and Trp53 tumor suppressor genes in colon epithelial cells and by orthotopic transplantation of Apc-edited colon organoids...
June 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28458955/prolonged-energy-harvesting-for-ingestible-devices
#14
Phillip Nadeau, Dina El-Damak, Dean Glettig, Yong Lin Kong, Stacy Mo, Cody Cleveland, Lucas Booth, Niclas Roxhed, Robert Langer, Anantha P Chandrakasan, Giovanni Traverso
Ingestible electronics have revolutionized the standard of care for a variety of health conditions. Extending the capacity and safety of these devices, and reducing the costs of powering them, could enable broad deployment of prolonged monitoring systems for patients. Although prior biocompatible power harvesting systems for in vivo use have demonstrated short minute-long bursts of power from the stomach, not much is known about the capacity to power electronics in the longer term and throughout the gastrointestinal tract...
2017: Nature biomedical engineering
https://www.readbyqxmd.com/read/28447624/wireless-power-transfer-to-millimeter-sized-gastrointestinal-electronics-validated-in-a-swine-model
#15
Abubakar Abid, Jonathan M O'Brien, Taylor Bensel, Cody Cleveland, Lucas Booth, Brian R Smith, Robert Langer, Giovanni Traverso
Electronic devices placed in the gastrointestinal (GI) tract for prolonged periods have the potential to transform clinical evaluation and treatment. One challenge to the deployment of such gastroresident electronics is the difficulty in powering millimeter-sized electronics devices without using batteries, which compromise biocompatibility and long-term residence. We examined the feasibility of leveraging mid-field wireless powering to transfer power from outside of the body to electronics at various locations along the GI tract...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436968/metabolic-control-of-primed-human-pluripotent-stem-cell-fate-and-function-by-the-mir-200c-sirt2-axis
#16
Young Cha, Min-Joon Han, Hyuk-Jin Cha, Janet Zoldan, Alison Burkart, Jin Hyuk Jung, Yongwoo Jang, Chun-Hyung Kim, Ho-Chang Jeong, Byung-Gyu Kim, Robert Langer, C Ronald Kahn, Leonard Guarente, Kwang-Soo Kim
A hallmark of cancer cells is the metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon referred to as the 'Warburg effect', which is also observed in primed human pluripotent stem cells (hPSCs). Here, we report that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature of primed hPSCs and that SIRT2 critically regulates metabolic reprogramming during induced pluripotency by targeting glycolytic enzymes including aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28409544/hypoxia-and-the-hypoxia-regulated-transcription-factor-hif-1%C3%AE-suppress-the-host-defence-of-airway-epithelial-cells
#17
Markus Polke, Frederik Seiler, Philipp M Lepper, Andreas Kamyschnikow, Frank Langer, Dominik Monz, Christian Herr, Robert Bals, Christoph Beisswenger
Chronic diseases of the respiratory tract, such as cystic fibrosis, are associated with mucosal and systemic hypoxia. Innate immune functions of airway epithelial cells are required to prevent and control infections of the lung parenchyma. The transcription factor hypoxia-inducible factor 1α (HIF-1α) regulates cellular adaptation to low oxygen conditions. Here, we show that hypoxia and HIF-1α regulate innate immune mechanisms of cultured human bronchial epithelial cells (HBECs). Exposure of primary HBECs to hypoxia or the prolyl hydroxylase inhibitor dimethyloxaloylglycine (DMOG) resulted in a significantly decreased expression of inflammatory mediators (IL-6, IFN-γ-induced protein 10) in response to ligands for TLRs (flagellin, polyI:C) and Pseudomonas aeruginosa, whereas the expression of inflammatory mediators was not affected by hypoxia or DMOG in the absence of microbial factors...
May 2017: Innate Immunity
https://www.readbyqxmd.com/read/28377441/percutaneous-transfemoral-tricuspid-valve-edge-to-edge-repair-a-case-series
#18
Karin Müller, Rezo Jorbenadze, Tobias Walker, Robert Schüler, Christoph Hammerstingl, Christian Schlensak, Meinrad Gawaz, Harald F Langer, Peter Seizer
No abstract text is available yet for this article.
April 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28353188/feasibility-of-standardized-methods-to-specify-behavioral-pediatric-obesity-prevention-interventions
#19
Meghan M JaKa, Simone A French, Julian Wolfson, Robert W Jeffery, Fabianna Lorencatto, Susan Michie, Shelby L Langer, Rona L Levy, Nancy E Sherwood
Standardized methods are needed to evaluate what occurs within the 'black box' of behavioral interventions to prevent pediatric obesity. The purpose of this research is to evaluate methods to specify the behavior change techniques used and the amount of time spent discussing target weight-related behaviors in an intervention for parents of children at risk for becoming overweight or obese. Independent coders were trained to identify behavior change techniques and time spent discussing weight-related behaviors in audio recordings and transcripts of intervention sessions from 100 randomly selected participants...
March 28, 2017: Journal of Behavioral Medicine
https://www.readbyqxmd.com/read/28333908/tuberculosis-united-states-2016
#20
Kristine M Schmit, Zimy Wansaula, Robert Pratt, Sandy F Price, Adam J Langer
In 2016, a total of 9,287 new tuberculosis (TB) cases were reported in the United States; this provisional* count represents the lowest number of U.S. TB cases on record and a 2.7% decrease from 2015 (1). The 2016 TB incidence of 2.9 cases per 100,000 persons represents a slight decrease compared with 2015 (-3.4%) (Figure). However, epidemiologic modeling demonstrates that if similar slow rates of decline continue, the goal of U.S. TB elimination will not be reached during this century (2). Although current programs to identify and treat active TB disease must be maintained and strengthened, increased measures to identify and treat latent TB infection (LTBI) among populations at high risk are also needed to accelerate progress toward TB elimination...
March 24, 2017: MMWR. Morbidity and Mortality Weekly Report
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