The David H. Koch Institute for Integrative Cancer Research at MITThe David H. Koch Institute for Integrative Cancer Research at MIT

Massachusetts Institute of Technology

National Cancer Institute Cancer Center

Science + Engineering... Conquering Cancer Together

Progress: October 2016

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1. In vitro and ex vivo strategies for intracellular delivery. Stewart MP, Sharei A, Ding X, Sahay G, Langer R, Jensen KF. Naturepubmed:27734871;  doi:10.1038/nature19764

2. A DOCK8-WIP-WASp complex links T cell receptors to the actin cytoskeleton. Janssen E, Tohme M, Hedayat M, Leick M, Kumari S, Ramesh N, Massaad MJ, Ullas S, Azcutia V, Goodnow CC, Randall KL, Qiao Q, Wu H, Al-Herz W, Cox D, Hartwig J, Irvine DJ, Luscinskas FW, Geha RS. J Clin Investpubmed:27599296;  doi:10.1172/JCI85774

3. Systematic Analysis of Quantitative Logic Model Ensembles Predicts Drug Combination Effects on Cell Signaling Networks. Morris MK, Clarke DC, Osimiri LC, Lauffenburger DA. CPT Pharmacometrics Syst Pharmacolpubmed:27567007;  doi:10.1002/psp4.12104

4. Synergistic Communication between CD4+ T Cells and Monocytes Impacts the Cytokine Environment. Schrier SB, Hill AS, Plana D, Lauffenburger DA. Sci Rep.pubmed:27721433;  doi:10.1038/srep34942

5. Magnetically Actuated Protease Sensors for in Vivo Tumor Profiling. Schuerle S, Dudani JS, Christiansen MG, Anikeeva P, Bhatia SN. Nano Lett.pubmed:27622711;  doi:10.1021/acs.nanolett.6b02670

6. Quantitative assessment of population variability in hepatic drug metabolism using a perfused 3D human liver microphysiological system. Tsamandouras N, Kostrzewski T, Stokes CL, Griffith LG, Hughes DJ, Cirit M. J Pharmacol Exp Therpubmed:27760784;  doi:10.1124/jpet.116.237495

7. Nano Day: Celebrating the Next Decade of Nanoscience and Nanotechnology. Kagan CR, Fernandez LE, Gogotsi Y, Hammond PT, Hersam MC, Nel AE, Penner RM, Willson CG, Weiss PS.ACS Nanopubmed:27712059;  doi:10.1021/acsnano.6b06655

8. Synthetic Biogenesis of Bacterial Amyloid Nanomaterials with Tunable Inorganic-Organic Interfaces and Electrical Conductivity. Seker UO, Chen AY, Citorik RJ, Lu TK. ACS Synth Biol.pubmed:27794590;  doi:10.1021/acssynbio.6b00166

9. Kinetics of Change in Droplet Size during Nanoemulsion Formation. Gupta A, Narsimhan V, Hatton TA, Doyle PS. Langmuirpubmed:27728762;  doi:10.1021/acs.langmuir.6b01862

10. Target-independent variable region mediated effects on antibody clearance can be FcRn independent. Kelly RL, Yu Y, Sun T, Caffry I, Lynaugh H, Brown M, Jain T, Xu Y, Wittrup KD.MAbspubmed:27610650;  doi:10.1080/19420862.2016.1208330

11. Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses. Moynihan KD, Opel CF, Szeto GL, Tzeng A, Zhu EF, Engreitz JM, Williams RT, Rakhra K, Zhang MH, Rothschilds AM, Kumari S, Kelly RL, Kwan BH, Abraham W, Hu K, Mehta NK, Kauke MJ, Suh H, Cochran JR, Lauffenburger DA, Wittrup KD, Irvine DJ. Nat Medpubmed:27775706;  doi:10.1038/nm.4200

12. Genital - Systemic chemokine gradients and the risk of HIV acquisition in women. Liebenberg LJ, Masson L, Arnold KB, Mckinnon LR, Werner L, Proctor E, Archary D, Mansoor LE, Lauffenburger DA, Abdool Karim Q, Abdool Karim SS, Passmore JS. J Acquir Immune Defic Syndrpubmed:27787345;  doi:10.1097/QAI.0000000000001218

13. The alternatively-included 11a sequence modifies the effects of Mena on actin cytoskeletal organization and cell behavior. Balsamo M, Mondal C, Carmona G, McClain LM, Riquelme DN, Tadros J, Ma D, Vasile E, Condeelis JS, Lauffenburger DA, Gertler FB. Sci Reppubmed:27748415;  doi:10.1038/srep35298

14. A Functional Role for Antibodies in Tuberculosis. Lu LL, Chung AW, Rosebrock TR, Ghebremichael M, Yu WH, Grace PS, Schoen MK, Tafesse F, Martin C, Leung V, Mahan AE, Sips M, Kumar MP, Tedesco J, Robinson H, Tkachenko E, Draghi M, Freedberg KJ, Streeck H, Suscovich TJ, Lauffenburger DA, Restrepo BI, Day C, Fortune SM, Alter G. Cell.pubmed:27667685;  doi:10.1016/j.cell.2016.08.072

15. MenaINV mediates synergistic crosstalk between signaling pathways driving chemotaxis and haptotaxis. Oudin MJ, Miller MA, Klazen JA, Kosciuk T, Lussiez A, Hughes SK, Tadros J, Bear JE, Lauffenburger DA, Gertler FB. Mol Biol Cellpubmed:27559126;  doi:10.1091/mbc.E16-04-0212

16. Polymer-Lipid Nanoparticles for Systemic Delivery of mRNA to the Lungs. Kaczmarek JC, Patel AK, Kauffman KJ, Fenton OS, Webber MJ, Heartlein MW, DeRosa F, Anderson DG. Angew Chem Int Ed Englpubmed:27690187;  doi:10.1002/anie.201608450

17. Engineering nanolayered particles for modular drug delivery. Correa S, Dreaden EC, Gu L, Hammond PT. J Control Releasepubmed:26809005;  doi:10.1016/j.jconrel.2016.01.040

18. Materials for Non-viral intracellular delivery of messenger RNA therapeutics. Kauffman KJ, Webber MJ, Anderson DG. J Control Release.pubmed:26718856;  doi:10.1016/j.jconrel.2015.12.032

19. Comparison of Modular PEG Incorporation Strategies for Stabilization of Peptide-siRNA Nanocomplexes. Lo JH, Kwon EJ, Zhang AQ, Singhal P, Bhatia SN. Bioconjug Chem.pubmed:27583545;  doi:10.1021/acs.bioconjchem.6b00304

20. High-Throughput Platform for Identifying Molecular Factors Involved in Phenotypic Stabilization of Primary Human Hepatocytes In Vitro. Shan J, Logan DJ, Root DE, Carpenter AE, Bhatia SN. J Biomol Screenpubmed:27650791;  doi:10.1177/1087057116660277

21. Infection of laboratory colonies of Anopheles mosquitoes with Plasmodium vivax from cryopreserved clinical isolates. Shaw-Saliba K, Clarke D, Santos JM, Menezes MJ, Lim C, Mascarenhas A, Chery L, Gomes E, March S, Bhatia SN, Rathod PK, Ferreira MU, Catteruccia F, Duraisingh MT. Int J Parasitolpubmed:27456552;  doi:10.1016/j.ijpara.2016.06.003

22. Pulsatility and high shear stress deteriorate barrier phenotype in brain microvascular endothelium. Garcia-Polite F, Martorell J, Del Rey-Puech P, Melgar-Lesmes P, O'Brien CC, Roquer J, Ois A, Principe A, Edelman ER, Balcells M. J Cereb Blood Flow Metabpubmed:27702879;  doi:10.1177/0271678X16672482

23. Design principles for reagentless biosensors: Specific fluorophore/analyte binding and minimization of fluorophore/scaffold interactions. de Picciotto S, Dickson PM, Traxlmayr MW, Marques BS, Socher E, Zhao S, Cheung S, Kiefer J, Wand AJ, Griffith LG, Imperiali B, Wittrup KD. J Mol Biolpubmed:27448945;  doi:10.1016/j.jmb.2016.07.004

24. Evaluation and Stability of PEDOT Polymer Electrodes for Li-O2 Batteries. Amanchukwu CV, Gauthier M, Batcho TP, Symister C, Shao-Horn Y, D'Arcy JM, Hammond PT. J Phys Chem Lett.pubmed:27610456;  doi:10.1021/acs.jpclett.6b01986

25. Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination. Tam HH, Melo MB, Kang M, Pelet JM, Ruda VM, Foley MH, Hu JK, Kumari S, Crampton J, Baldeon AD, Sanders RW, Moore JP, Crotty S, Langer R, Anderson DG, Chakraborty AK, Irvine DJ. Proc Natl Acad Sci U S Apubmed:27702895;  doi:10.1073/pnas.1606050113

26. Progress in Formulation-Based Approaches for Antiretrovirals. Kirtane AR, Langer R, Traverso G. J Pharm Scipubmed:27771050;  doi:10.1016/j.xphs.2016.09.015

27. Nanoparticle-based drug delivery systems: a commercial and regulatory outlook as the field matures. Ragelle H, Danhier F, Preat V, Langer R, Anderson DG. Expert Opin Drug Deliv.pubmed:27730820;  doi:10.1080/17425247.2016.1244187

28. Interaction between integrin alpha5 and PDE4D regulates endothelial inflammatory signalling. Yun S, Budatha M, Dahlman JE, Coon BG, Cameron RT, Langer R, Anderson DG, Baillie G, Schwartz MA. Nat Cell Biolpubmed:27595237;  doi:10.1038/ncb3405

29. A decade of progress in tissue engineering. Khademhosseini A, Langer R. Nat Protocpubmed:27583639;  doi:10.1038/nprot.2016.123

30. High-throughput measurement of single-cell growth rates using serial microfluidic mass sensor arrays. Cermak N, Olcum S, Delgado FF, Wasserman SC, Payer KR, A Murakami M, Knudsen SM, Kimmerling RJ, Stevens MM, Kikuchi Y, Sandikci A, Ogawa M, Agache V, Baleras F, Weinstock DM, Manalis SR. Nat Biotechnolpubmed:27598230;  doi:10.1038/nbt.3666

31. Generation of long-lived bone marrow plasma cells secreting antibodies specific for HIV-1 gp41 MPER in the absence of polyreactivity. Donius LR, Cheng Y, Choi J, Sun ZJ, Hanson M, Zhang M, Gierahn TM, Marquez S, Uduman M, Kleinstein SH, Irvine D, Love JC, Reinherz EL, Kim M. J Virolpubmed:27466419;  doi:10.1128/JVI.01089-16

32. Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate. Stevens MM, Maire CL, Chou N, Murakami MA, Knoff DS, Kikuchi Y, Kimmerling RJ, Liu H, Haidar S, Calistri NL, Cermak N, Olcum S, Cordero NA, Idbaih A, Wen PY, Weinstock DM, Ligon KL, Manalis SR. Nat Biotechnolpubmed:27723727;  doi:10.1038/nbt.3697

33. Glycan-protein interactions in viral pathogenesis. Raman R, Tharakaraman K, Sasisekharan V, Sasisekharan R. Curr Opin Struct Biolpubmed:27792989;  doi:10.1016/j.sbi.2016.10.003

34. A Structural and Mathematical Modeling Analysis of the Likelihood of Antibody-Dependent Enhancement in Influenza. Ramakrishnan B, Viswanathan K, Tharakaraman K, Dancik V, Raman R, Babcock GJ, Shriver Z, Sasisekharan R. Trends Microbiolpubmed:27751627;  doi:10.1016/j.tim.2016.09.003

35. Activity of caffeic acid phenethyl ester in Caenorhabditis elegans. Coleman JJ, Komura T, Munro J, Wu MP, Busanelli RR, Koehler AN, Thomas M, Wagner FF, Holson EB, Mylonakis E.Future Med Chempubmed:27739327;  doi:10.4155/fmc-2016-0085

36. A Novel Small Molecule Activator of Nuclear Receptor SHP Inhibits HCC Cell Migration via Suppressing Ccl2. Yang Z, Koehler AN, Wang L. Mol Cancer Ther.pubmed:27486225;  doi:10.1158/1535-7163.MCT-16-0153

37. Deciphering Combinatorial Genetics. Wong AS, Choi GC, Lu TK. Annu Rev Genetpubmed:27732793;  doi:10.1146/annurev-genet-120215-034902

38. Microbiome therapeutics - Advances and challenges. Mimee M, Citorik RJ, Lu TK. Adv Drug Deliv Revpubmed:27158095;  doi:10.1016/j.addr.2016.04.032

39. DNA repair capacity in multiple pathways predicts chemoresistance in glioblastoma multiforme. Nagel ZD, Kitange GJ, Gupta SK, Joughin BA, Chaim IA, Mazzucato P, Lauffenburger DA, Sarkaria JN, Samson LD. Cancer Respubmed:27793847;  doi:10.1158/0008-5472.CAN-16-1151

40. Identification of new branch points and unconventional introns in Saccharomyces cerevisiae. Gould GM, Paggi JM, Guo Y, Phizicky DV, Zinshteyn B, Wang ET, Gilbert WV, Gifford DK, Burge CB. RNApubmed:27473169;  doi:10.1261/rna.057216.116

41. Local regulation of gene expression by lncRNA promoters, transcription and splicing. Engreitz JM, Haines JE, Perez EM, Munson G, Chen J, Kane M, McDonel PE, Guttman M, Lander ES.Naturepubmed:27783602;  doi:10.1038/nature20149

42. A G-Rich Motif in the lncRNA Braveheart Interacts with a Zinc-Finger Transcription Factor to Specify the Cardiovascular Lineage. Xue Z, Hennelly S, Doyle B, Gulati AA, Novikova IV, Sanbonmatsu KY, Boyer LA. Mol Cellpubmed:27618485;  doi:10.1016/j.molcel.2016.08.010

43. Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System. Martinez FJ, Pratt GA, Van Nostrand EL, Batra R, Huelga SC, Kapeli K, Freese P, Chun SJ, Ling K, Gelboin-Burkhart C, Fijany L, Wang HC, Nussbacher JK, Broski SM, Kim HJ, Lardelli R, Sundararaman B, Donohue JP, Javaherian A, Lykke-Andersen J, Finkbeiner S, Bennett F, Ares MJr, Burge CB, Taylor JP, Rigo F, Yeo GW. Neuronpubmed:27773581;  doi:10.1016/j.neuron.2016.09.050

44. RNA Sequence Context Effects Measured In Vitro Predict In Vivo Protein Binding and Regulation. Taliaferro JM, Lambert NJ, Sudmant PH, Dominguez D, Merkin JJ, Alexis MS, Bazile CA, Burge CB. Mol Cellpubmed:27720642;  doi:10.1016/j.molcel.2016.08.035

45. CNS disease models with human pluripotent stem cells in the CRISPR age. Muffat J, Li Y, Jaenisch R. Curr Opin Cell Biolpubmed:27768957;  doi:10.1016/j.ceb.2016.10.001

46. Molecular Criteria for Defining the Naive Human Pluripotent State. Theunissen TW, Friedli M, He Y, Planet E, O'Neil RC, Markoulaki S, Pontis J, Wang H, Iouranova A, Imbeault M, Duc J, Cohen MA, Wert KJ, Castanon R, Zhang Z, Huang Y, Nery JR, Drotar J, Lungjangwa T, Trono D, Ecker JR, Jaenisch R. Cell Stem Cellpubmed:27424783;  doi:10.1016/j.stem.2016.06.011

47. A widely employed germ cell marker is an ancient disordered protein with reproductive functions in diverse eukaryotes. Carmell MA, Dokshin GA, Skaletsky H, Hu YC, von Wolfswinkel JC, Igarashi KJ, Bellott DW, Nefedov M, Reddien PW, Enders GC, Uversky VN, Mello CC, Page DC. Elifepubmed:27718356;  doi:10.7554/eLife.19993

48. Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors. Zhang T, Kwiatkowski N, Olson CM, Dixon-Clarke SE, Abraham BJ, Greifenberg AK, Ficarro SB, Elkins JM, Liang Y, Hannett NM, Manz T, Hao M, Bartkowiak B, Greenleaf AL, Marto JA, Geyer M, Bullock AN, Young RA, Gray NS. Nat Chem Biol.pubmed:27571479;  doi:10.1038/nchembio.2166

49. Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas. Clark VE, Harmanci AS, Bai H, Youngblood MW, Lee TI, Baranoski JF, Ercan-Sencicek AG, Abraham BJ, Weintraub AS, Hnisz D, Simon M, Krischek B, Erson-Omay EZ, Henegariu O, Carrion-Grant G, Mishra-Gorur K, Duran D, Goldmann JE, Schramm J, Goldbrunner R, Piepmeier JM, Vortmeyer AO, Gunel JM, Bilguvar K, Yasuno K, Young RA, Gunel M. Nat Genetpubmed:27548314;  doi:10.1038/ng.3651

50. Striosome-dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons. Crittenden JR, Tillberg PW, Riad MH, Shima Y, Gerfen CR, Curry J, Housman DE, Nelson SB, Boyden ES, Graybiel AM. Proc Natl Acad Sci U S Apubmed:27647894;  doi:10.1073/pnas.1613337113

51. TGF-beta inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors. Gao X, Lee HY, da Rocha EL, Zhang C, Lu YF, Li D, Feng Y, Ezike J, Elmes RR, Barrasa MI, Cahan P, Li H, Daley GQ, Lodish HF. Bloodpubmed:27777239;  doi:10.1182/blood-2016-05-718320

52. Molecular Pathways: Dietary regulation of stemness and tumor initiation by the PPAR-delta pathway. Yilmaz OH, Beyaz S. Clin Cancer Respubmed:27702819;  doi:10.1158/1078-0432.CCR-16-0775

53. Sirtuin 1 Promotes Deacetylation of Oct4 and Maintenance of Naive Pluripotency. Williams EO, Taylor AK, Bell EL, Lim R, Kim DM, Guarente L. Cell Rep.pubmed:27732856;  doi:10.1016/j.celrep.2016.09.046

54. Overcoming ATM Deficiency by Activating the NAD+/SIRT1 Axis. Guarente L. Cell Metabpubmed:27732834;  doi:10.1016/j.cmet.2016.09.019

55. LTE1 promotes Exit from Mitosis by multiple mechanisms. Falk JE, Campbell IW, Joyce K, Whalen J, Seshan A, Amon A. Mol Biol Cellpubmed:27798238;  doi:10.1091/mbc.E16-08-0563

56. Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma. McFadden DG, Politi K, Bhutkar A, Chen FK, Song X, Pirun M, Santiago PM, Kim-Kiselak C, Platt JT, Lee E, Hodges E, Rosebrock AP, Bronson RT, Socci ND, Hannon GJ, Jacks T, Varmus H. Proc Natl Acad Sci U S A.pubmed:27702896;  doi:10.1073/pnas.1613601113

57. Intrinsically Disordered Proteins Drive Emergence and Inheritance of Biological Traits. Chakrabortee S, Byers JS, Jones S, Garcia DM, Bhullar B, Chang A, She R, Lee L, Fremin B, Lindquist S, Jarosz DF. Cellpubmed:27693355;  doi:10.1016/j.cell.2016.09.017

58. Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an alpha-glucosidase inhibitor or a Nrf2-inducer. Strong R, Miller RA, Antebi A, Astle CM, Bogue M, Denzel MS, Fernandez E, Flurkey K, Hamilton KL, Lamming DW, Javors MA, de Magalhaes JP, Marinez PA, McCord JM, Miller BF, Muller M, Nelson JF, Ndukum J, Rainger GE, Richardson A, Sabatini DM, Salmon AB, Simpkins JW, Steegenga WT, Nadon NL, Harrison DE. Aging Cellpubmed:27312235;  doi:10.1111/acel.12496

59. Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. Gui DY, Sullivan LB, Luengo A, Hosios AM, Bush LN, Gitego N, Davidson SM, Freinkman E, Thomas CJ, Vander Heiden MG. Cell Metabpubmed:27746050;  doi:10.1016/j.cmet.2016.09.006

60. Critical Functions of the Lysosome in Cancer Biology. Davidson SM, Vander Heiden MG. Annu Rev Pharmacol Toxicolpubmed:27732799;  doi:10.1146/annurev-pharmtox-010715-103101

61. The breast cancer stem cell potency of copper(ii) complexes bearing nonsteroidal anti-inflammatory drugs and their encapsulation using polymeric nanoparticles. Eskandari A, Boodram JN, Cressey PB, Lu C, Bruno PM, Hemann MT, Suntharalingam K. Dalton Transpubmed:27774561;  doi:10.1039/c6dt03811e

62. Phenanthriplatin Acts as a Covalent Poison of Topoisomerase II Cleavage Complexes. Riddell IA, Agama K, Park GY, Pommier Y, Lippard SJ. ACS Chem Biol.pubmed:27648475;  doi:10.1021/acschembio.6b00565