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: September 2016

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1. HIV Vaccine Design to Target Germline Precursors of Glycan-Dependent Broadly Neutralizing Antibodies. Steichen JM, Kulp DW, Tokatlian T, Escolano A, Dosenovic P, Stanfield RL, McCoy LE, Ozorowski G, Hu X, Kalyuzhniy O, Briney B, Schiffner T, Garces F, Freund NT, Gitlin AD, Menis S, Georgeson E, Kubitz M, Adachi Y, Jones M, Mutafyan AA, Yun DS, Mayer CT, Ward AB, Burton DR, Wilson IA, Irvine DJ, Nussenzweig MC, Schief WR. Immunitypubmed:27617678;  doi:10.1016/j.immuni.2016.08.016

2. Comparative analysis of bispecific antibody and streptavidin-targeted radioimmunotherapy for B cell cancers. Green DJ, Frayo SL, Lin Y, Hamlin DK, Fisher DR, Frost SH, Kenoyer AL, Hylarides MD, Gopal AK, Gooley TA, Orozco JJ, Till BG, O'Steen S, Orcutt KD, Wilbur DS, Wittrup KD, Press OW. Cancer Respubmed:27590740;  doi:10.1158/0008-5472.CAN-16-0571

3. Modeling therapeutic antibody-small molecule drug-drug interactions using a 3D perfusable human liver co-culture platform. Long TJ, Cosgrove PA, Dunn RT, Stolz DB, Hamadeh HK, Afshari C, McBride H, Griffith LG. Drug Metab Dispospubmed:27621203;  doi:10.1124/dmd.116.071456

4. Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract. Zevin AS, Xie IY, Birse K, Arnold K, Romas L, Westmacott G, Novak RM, McCorrister S, McKinnon LR, Cohen CR, Mackelprang R, Lingappa J, Lauffenburger DA, Klatt NR, Burgener AD. PLoS Pathog.pubmed:27656899;  doi:10.1371/journal.ppat.1005889

5. GPS for QSP: A Summary of the ACoP6 Symposium on Quantitative Systems Pharmacology and a Stage for Near-Term Efforts in the Field. Musante CJ, Abernethy DR, Allerheiligen SR, Lauffenburger DA, Zager MG. CPT Pharmacometrics Syst Pharmacolpubmed:27639191;  doi:10.1002/psp4.12109

6. Revealing disease-associated pathways by network integration of untargeted metabolomics. Pirhaji L, Milani P, Leidl M, Curran T, Avila-Pacheco J, Clish CB, White FM, Saghatelian A, Fraenkel E. Nat Methodspubmed:27479327;  doi:10.1038/nmeth.3940

7. 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

8. Proliferation and Recruitment Contribute to Myocardial Macrophage Expansion in Chronic Heart Failure. Sager HB, Hulsmans M, Lavine KJ, Beltrami Moreira MB, Heidt T, Courties G, Sun Y, Iwamoto Y, Tricot B, Khan OF, Dahlman JE, Borodovsky A, Fitzgerald K, Anderson DG, Weissleder R, Libby P, Swirski FK, Nahrendorf M. Circ Res.pubmed:27444755;  doi:10.1161/CIRCRESAHA.116.309001

9. Diversity-oriented synthesis yields novel multistage antimalarial inhibitors. Kato N, Comer E, Sakata-Kato T, Sharma A, Sharma M, Maetani M, Bastien J, Brancucci NM, Bittker JA, Corey V, Clarke D, Derbyshire ER, Dornan G, Duffy S, Eckley S, Itoe MA, Koolen KM, Lewis TA, Lui PS, Lukens AK, Lund E, March S, Meibalan E, Meier BC, McPhail J, Mitasev B, Moss EL, Sayes M, VanGessel Y, Wawer MJ, Yoshinaga T, Zeeman AM, Avery VM, Bhatia SN, Burke JE, Catteruccia F, Clardy JC, Clemons PA, Dechering KJ, Duvall JR, Foley MA, Gusovsky F, Kocken CH, Marti M, Morningstar ML, Munoz B, Neafsey DE, Sharma A, Winzeler EA, Wirth DF, Scherer CA, Schreiber SL. Nature.pubmed:27602946;  doi:10.1038/nature19804

10. Host AMPK Is a Modulator of Plasmodium Liver Infection. Ruivo MT, Vera IM, Sales-Dias J, Meireles P, Gural N, Bhatia SN, Mota MM, Mancio-Silva L. Cell Rep.pubmed:27568570;  doi:10.1016/j.celrep.2016.08.001

11. Development of Light-Activated CRISPR Using Guide RNAs with Photocleavable Protectors. Jain PK, Ramanan V, Schepers AG, Dalvie NS, Panda A, Fleming HE, Bhatia SN. Angew Chem Int Ed Englpubmed:27554600;  doi:10.1002/anie.201606123

12. Self-Sealing Porous Silicon-Calcium Silicate Core-Shell Nanoparticles for Targeted siRNA Delivery to the Injured Brain. Kang J, Joo J, Kwon EJ, Skalak M, Hussain S, She ZG, Ruoslahti E, Bhatia SN, Sailor MJ. Adv Materpubmed:27383373;  doi:10.1002/adma.201600634

13. Elimination of Transcoarctation Pressure Gradients Has No Impact on Left Ventricular Function or Aortic Shear Stress After Intervention in Patients With Mild Coarctation. Keshavarz-Motamed Z, Rikhtegar Nezami F, Partida RA, Nakamura K, Staziaki PV, Ben-Assa E, Ghoshhajra B, Bhatt AB, Edelman ER. JACC Cardiovasc Interv.pubmed:27659574;  doi:10.1016/j.jcin.2016.06.054

14. Effects of Low Endothelial Shear Stress After Stent Implantation on Subsequent Neointimal Hyperplasia and Clinical Outcomes in Humans. Shishido K, Antoniadis AP, Takahashi S, Tsuda M, Mizuno S, Andreou I, Papafaklis MI, Coskun AU, O'Brien C, Feldman CL, Saito S, Edelman ER, Stone PH. J Am Heart Assoc.pubmed:27628570;  doi:10.1161/JAHA.115.002949

15. Atherosclerotic plaque behind the stent changes after bare-metal and drug-eluting stent implantation in humans: Implications for late stent failure. Andreou I, Takahashi S, Tsuda M, Shishido K, Antoniadis AP, Papafaklis MI, Mizuno S, Coskun AU, Saito S, Feldman CL, Edelman ER, Stone PH. Atherosclerosis.pubmed:27494445;  doi:10.1016/j.atherosclerosis.2016.07.914

16. Drug deposition in coronary arteries with overlapping drug-eluting stents. Rikhtegar F, Edelman ER, Olgac U, Poulikakos D, Kurtcuoglu V. J Control Release.pubmed:27432751;  doi:10.1016/j.jconrel.2016.07.023

17. Layer-by-Layer Encapsulation of Probiotics for Delivery to the Microbiome. Anselmo AC, McHugh KJ, Webster J, Langer R, Jaklenec A. Adv Mater.pubmed:27616140;  doi:10.1002/adma.201603270

18. Application of Targeted Molecular and Material Property Optimization to Bacterial Attachment-Resistant (Meth)acrylate Polymers. Adlington K, Nguyen NT, Eaves E, Yang J, Chang CY, Li J, Gower AL, Stimpson A, Anderson DG, Langer R, Davies MC, Hook AL, Williams P, Alexander MR, Irvine DJ. Biomacromolecules.pubmed:27461341;  doi:10.1021/acs.biomac.6b00615

19. Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy. Detappe A, Kunjachan S, Sancey L, Motto-Ros V, Biancur D, Drane P, Guieze R, Makrigiorgos GM, Tillement O, Langer R, Berbeco R. J Control Releasepubmed:27423325;  doi:10.1016/j.jconrel.2016.07.021

20. A Size-Selective Intracellular Delivery Platform. Saung MT, Sharei A, Adalsteinsson VA, Cho N, Kamath T, Ruiz C, Kirkpatrick J, Patel N, Mino-Kenudson M, Thayer SP, Langer R, Jensen KF, Liss AS, Love JC. Smallpubmed:27594517;  doi:10.1002/smll.201601155

21. Synthetic Morphogenesis. Teague BP, Guye P, Weiss R. Cold Spring Harb Perspect Biolpubmed:27270296;  doi:10.1101/cshperspect.a023929

22. Porous microwells for geometry-selective, large-scale microparticle arrays. Kim JJ, Bong KW, Reategui E, Irimia D, Doyle PS. Nat Mater.pubmed:27595351;  doi:10.1038/nmat4747

23. Continuous genetic recording with self-targeting CRISPR-Cas in human cells. Perli SD, Cui CH, Lu TK. Sciencepubmed:27540006;  doi:10.1126/science.aag0511

24. Genetically Engineered Phages: a Review of Advances over the Last Decade. Pires DP, Cleto S, Sillankorva S, Azeredo J, Lu TK. Microbiol Mol Biol Rev.pubmed:27250768;  doi:10.1128/MMBR.00069-15

25. 52 Genetic Loci Influencing Myocardial Mass. van der Harst P, van Setten J, Verweij N, Vogler G, Franke L, Maurano MT, Wang X, Mateo Leach I, Eijgelsheim M, Sotoodehnia N, Hayward C, Sorice R, Meirelles O, Lyytikainen LP, Polasek O, Tanaka T, Arking DE, Ulivi S, Trompet S, Muller-Nurasyid M, Smith AV, Dorr M, Kerr KF, Magnani JW, Del Greco MF, Zhang W, Nolte IM, Silva CT, Padmanabhan S, Tragante V, Esko T, Abecasis GR, Adriaens ME, Andersen K, Barnett P, Bis JC, Bodmer R, Buckley BM, Campbell H, Cannon MV, Chakravarti A, Chen LY, Delitala A, Devereux RB, Doevendans PA, Dominiczak AF, Ferrucci L, Ford I, Gieger C, Harris TB, Haugen E, Heinig M, Hernandez DG, Hillege HL, Hirschhorn JN, Hofman A, Hubner N, Hwang SJ, Iorio A, Kahonen M, Kellis M, Kolcic I, Kooner IK, Kooner JS, Kors JA, Lakatta EG, Lage K, Launer LJ, Levy D, Lundby A, Macfarlane PW, May D, Meitinger T, Metspalu A, Nappo S, Naitza S, Neph S, Nord AS, Nutile T, Okin PM, Olsen JV, Oostra BA, Penninger JM, Pennacchio LA, Pers TH, Perz S, Peters A, Pinto YM, Pfeufer A, Pilia MG, Pramstaller PP, Prins BP, Raitakari OT, Raychaudhuri S, Rice KM, Rossin EJ, Rotter JI, Schafer S, Schlessinger D, Schmidt CO, Sehmi J, Sillje HH, Sinagra G, Sinner MF, Slowikowski K, Soliman EZ, Spector TD, Spiering W, Stamatoyannopoulos JA, Stolk RP, Strauch K, Tan ST, Tarasov KV, Trinh B, Uitterlinden AG, van den Boogaard M, van Duijn CM, van Gilst WH, Viikari JS, Visscher PM, Vitart V, Volker U, Waldenberger M, Weichenberger CX, Westra HJ, Wijmenga C, Wolffenbuttel BH, Yang J, Bezzina CR, Munroe PB, Snieder H, Wright AF, Rudan I, Boyer LA, Asselbergs FW, van Veldhuisen DJ, Stricker BH, Psaty BM, Ciullo M, Sanna S, Lehtimaki T, Wilson JF, Bandinelli S, Alonso A, Gasparini P, Jukema JW, Kaab S, Gudnason V, Felix SB, Heckbert SR, de Boer RA, Newton-Cheh C, Hicks AA, Chambers JC, Jamshidi Y, Visel A, Christoffels VM, Isaacs A, Samani NJ, de Bakker PI. J Am Coll Cardiolpubmed:27659466;  doi:10.1016/j.jacc.2016.07.729

26. 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

27. Widespread Shortening of 3' Untranslated Regions and Increased Exon Inclusion Are Evolutionarily Conserved Features of Innate Immune Responses to Infection. Pai AA, Baharian G, Page Sabourin A, Brinkworth JF, Nedelec Y, Foley JW, Grenier JC, Siddle KJ, Dumaine A, Yotova V, Johnson ZP, Lanford RE, Burge CB, Barreiro LB. PLoS Genet.pubmed:27690314;  doi:10.1371/journal.pgen.1006338

28. Targeting Epstein-Barr virus transformed B lymphoblastoid cells using antibodies with T cell receptor-like specificities. Lai J, Tan WJ, Too CT, Choo JA, Wong LH, Bte Mustafa F, Srinivasan N, Lim AP, Zhong Y, Gascoigne NR, Hanson BJ, Chan SH, Chen J, MacAry PA. Bloodpubmed:27338099;  doi:10.1182/blood-2016-03-707836

29. Efficient derivation of microglia-like cells from human pluripotent stem cells. Muffat J, Li Y, Yuan B, Mitalipova M, Omer A, Corcoran S, Bakiasi G, Tsai LH, Aubourg P, Ransohoff RM, Jaenisch R. Nat Medpubmed:27668937;  doi:10.1038/nm.4189

30. Parent-of-Origin DNA Methylation Dynamics during Mouse Development. Stelzer Y, Wu H, Song Y, Shivalila CS, Markoulaki S, Jaenisch R. Cell Rep.pubmed:27653683;  doi:10.1016/j.celrep.2016.08.066

31. Systematic mapping of functional enhancer-promoter connections with CRISPR interference. Fulco CP, Munschauer M, Anyoha R, Munson G, Grossman SR, Perez EM, Kane M, Cleary B, Lander ES, Engreitz JM. Sciencepubmed:27708057;  doi:10.1126/science.aag2445

32. Posttranscriptional Regulation of Glycoprotein Quality Control in the Endoplasmic Reticulum Is Controlled by the E2 Ub-Conjugating Enzyme UBC6e. Hagiwara M, Ling J, Koenig PA, Ploegh HL. Mol Cellpubmed:27570074;  doi:10.1016/j.molcel.2016.07.014

33. Editing DNA Methylation in the Mammalian Genome. Liu XS, Wu H, Ji X, Stelzer Y, Wu X, Czauderna S, Shu J, Dadon D, Young RA, Jaenisch R. Cell.pubmed:27662091;  doi:10.1016/j.cell.2016.08.056

34. Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features. Ouyang Q, Nakayama T, Baytas O, Davidson SM, Yang C, Schmidt M, Lizarraga SB, Mishra S, Ei-Quessny M, Niaz S, Gul Butt M, Imran Murtaza S, Javed A, Chaudhry HR, Vaughan DJ, Hill RS, Partlow JN, Yoo SY, Lam AN, Nasir R, Al-Saffar M, Barkovich AJ, Schwede M, Nagpal S, Rajab A, DeBerardinis RJ, Housman DE, Mochida GH, Morrow EM. Proc Natl Acad Sci U S A.pubmed:27601654;  doi:10.1073/pnas.1609221113

35. High-resolution interrogation of functional elements in the noncoding genome. Sanjana NE, Wright J, Zheng K, Shalem O, Fontanillas P, Joung J, Cheng C, Regev A, Zhang F.Sciencepubmed:27708104;  doi:10.1126/science.aaf7613

36. Protein C receptor (PROCR) is a negative regulator of Th17 pathogenicity. Kishi Y, Kondo T, Xiao S, Yosef N, Gaublomme J, Wu C, Wang C, Chihara N, Regev A, Joller N, Kuchroo VK. J Exp Medpubmed:27670590;  doi:10.1084/jem.20151118

37. Regulation of X-linked gene expression during early mouse development by Rlim. Wang F, Shin J, Shea JM, Yu J, Boskovic A, Byron M, Zhu X, Shalek AK, Regev A, Lawrence JB, Torres EM, Zhu LJ, Rando OJ, Bach I. Elifepubmed:27642011;  doi:10.7554/eLife.19127

38. Multiplexed, targeted profiling of single-cell proteomes and transcriptomes in a single reaction. Genshaft AS, Li S, Gallant CJ, Darmanis S, Prakadan SM, Ziegler CG, Lundberg M, Fredriksson S, Hong J, Regev A, Livak KJ, Landegren U, Shalek AK. Genome Biolpubmed:27640647;  doi:10.1186/s13059-016-1045-6

39. A Distinct Gene Module for Dysfunction Uncoupled from Activation in Tumor-Infiltrating T Cells. Singer M, Wang C, Cong L, Marjanovic ND, Kowalczyk MS, Zhang H, Nyman J, Sakuishi K, Kurtulus S, Gennert D, Xia J, Kwon JY, Nevin J, Herbst RH, Yanai I, Rozenblatt-Rosen O, Kuchroo VK, Regev A, Anderson AC. Cell.pubmed:27610572;  doi:10.1016/j.cell.2016.08.052

40. Clonal dynamics following p53 loss of heterozygosity in Kras-driven cancers. Muzumdar MD, Dorans KJ, Chung KM, Robbins R, Tammela T, Gocheva V, Li CM, Jacks T. Nat Communpubmed:27585860;  doi:10.1038/ncomms12685

41. A US "Cancer Moonshot" to accelerate cancer research. Singer DS, Jacks T, Jaffee E. Sciencepubmed:27605537;  doi:10.1126/science.aai7862

42. The apo-structure of the leucine sensor Sestrin2 is still elusive. Saxton RA, Knockenhauer KE, Schwartz TU, Sabatini DM. Sci Signal.pubmed:27649739;  doi:10.1126/scisignal.aah4497

43. Altered metabolite levels in cancer: implications for tumour biology and cancer therapy. Sullivan LB, Gui DY, Vander Heiden MG. Nat Rev Cancer.pubmed:27658530;  doi:10.1038/nrc.2016.85

44. Tissue of origin dictates branched-chain amino acid metabolism in mutant Kras-driven cancers. Mayers JR, Torrence ME, Danai LV, Papagiannakopoulos T, Davidson SM, Bauer MR, Lau AN, Ji BW, Dixit PD, Hosios AM, Muir A, Chin CR, Freinkman E, Jacks T, Wolpin BM, Vitkup D, Vander Heiden MG. Science.pubmed:27609895;  doi:10.1126/science.aaf5171

45. Glucose-dependent anaplerosis in cancer cells is required for cellular redox balance in the absence of glutamine. Cetinbas NM, Sudderth J, Harris RC, Cebeci A, Negri GL, Yilmaz OH, DeBerardinis RJ, Sorensen PH. Sci Reppubmed:27605385;  doi:10.1038/srep32606

46. Using an RNAi Signature Assay To Guide the Design of Three-Drug-Conjugated Nanoparticles with Validated Mechanisms, In Vivo Efficacy, and Low Toxicity. Barnes JC, Bruno PM, Nguyen HV, Liao L, Liu J, Hemann MT, Johnson JA. J Am Chem Socpubmed:27626288;  doi:10.1021/jacs.6b06321

47. Rewiring the solid tumor epigenome for cancer therapy. Braun CJ, Hemann MT. Expert Rev Anticancer Therpubmed:27410491;  doi:10.1080/14737140.2016.1212663

48. The Potent Inhibitory Effect of a Naproxen-Appended Cobalt(III)-Cyclam Complex on Cancer Stem Cells. Cressey P, Eskandari A, Bruno P, Lu C, Hemann M, Suntharalingam K. Chembiochempubmed:27377813;  doi:10.1002/cbic.201600368

49. 5'-Inositol phosphatase SHIP2 recruits Mena to stabilize invadopodia for cancer cell invasion. Rajadurai CV, Havrylov S, Coelho PP, Ratcliffe CD, Zaoui K, Huang BH, Monast A, Chughtai N, Sangwan V, Gertler FB, Siegel PM, Park M. J Cell Biolpubmed:27597754;  doi:10.1083/jcb.201501003

50. Chemical approach to positional isomers of glucose-platinum conjugates reveals specific cancer targeting through glucose-transporter mediated uptake in vitro and in vivo. Patra M, Awuah SG, Lippard SJ. J Am Chem Socpubmed:27570149;  doi:10.1021/jacs.6b06937

51. Disulfide cross-linking influences symbiotic activities of nodule peptide NCR247. Shabab M, Arnold MF, Penterman J, Wommack AJ, Bocker HT, Price PA, Griffitts JS, Nolan EM, Walker GC. Proc Natl Acad Sci U S Apubmed:27551097;  doi:10.1073/pnas.1610724113