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: June 2017

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1. Advances in the delivery of RNA therapeutics: from concept to clinical reality. Kaczmarek JC, Kowalski PS, Anderson DG. Genome Medpubmed:28655327;  doi:10.1186/s13073-017-0450-0

2. A Modular Toolkit for Generating Pichia pastoris Secretion Libraries. Obst U, Lu TK, Sieber V. ACS Synth Biolpubmed:28252957;  doi:10.1021/acssynbio.6b00337

3. Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches. Pauthner M, Havenar-Daughton C, Sok D, Nkolola JP, Bastidas R, Boopathy AV, Carnathan DG, Chandrashekar A, Cirelli KM, Cottrell CA, Eroshkin AM, Guenaga J, Kaushik K, Kulp DW, Liu J, McCoy LE, Oom AL, Ozorowski G, Post KW, Sharma SK, Steichen JM, de Taeye SW, Tokatlian T, Torrents de la Pena A, Butera ST, LaBranche CC, Montefiori DC, Silvestri G, Wilson IA, Irvine DJ, Sanders RW, Schief WR, Ward AB, Wyatt RT, Barouch DH, Crotty S, Burton DR. Immunitypubmed:28636956;  doi:10.1016/j.immuni.2017.05.007

4. Biopolymers codelivering engineered T cells and STING agonists can eliminate heterogeneous tumors. Smith TT, Moffett HF, Stephan SB, Opel CF, Dumigan AG, Jiang X, Pillarisetty VG, Pillai SPS, Wittrup KD, Stephan MT. J Clin Investpubmed:28436934;  doi:10.1172/JCI87624

5. Integrin-targeted cancer immunotherapy elicits protective adaptive immune responses. Kwan BH, Zhu EF, Tzeng A, Sugito HR, Eltahir AA, Ma B, Delaney MK, Murphy PA, Kauke MJ, Angelini A, Momin N, Mehta NK, Maragh AM, Hynes RO, Dranoff G, Cochran JR, Wittrup KD. J Exp Medpubmed:28473400;  doi:10.1084/jem.20160831

6. On-demand dissolution of modular, synthetic extracellular matrix reveals local epithelial-stromal communication networks. Valdez J, Cook CD, Ahrens CC, Wang AJ, Brown A, Kumar M, Stockdale L, Rothenberg D, Renggli K, Gordon E, Lauffenburger D, White F, Griffith L. Biomaterialspubmed:28371736;  doi:10.1016/j.biomaterials.2017.03.030

7. Identification of Novel Fibrosis Modifiers by In Vivo siRNA Silencing. Vollmann EH, Cao L, Amatucci A, Reynolds T, Hamann S, Dalkilic-Liddle I, Cameron TO, Hossbach M, Kauffman KJ, Mir FF, Anderson DG, Novobrantseva T, Koteliansky V, Kisseleva T, Brenner D, Duffield J, Burkly LC. Mol Ther Nucleic Acidspubmed:28624207;  doi:10.1016/j.omtn.2017.04.014

8. CRISPR/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion. Mou H, Smith JL, Peng L, Yin H, Moore J, Zhang XO, Song CQ, Sheel A, Wu Q, Ozata DM, Li Y, Anderson DG, Emerson CP, Sontheimer EJ, Moore MJ, Weng Z, Xue W. Genome Biolpubmed:28615073;  doi:10.1186/s13059-017-1237-8

9. First-Generation Bioresorbable Vascular Scaffolds: Disappearing Stents or Disappearing Evidence?. Bangalore S, Edelman ER, Bhatt DL. J Am Coll Cardiolpubmed:28412390;  doi:10.1016/j.jacc.2017.04.012

10. A versatile microfluidic device for high throughput production of microparticles and cell microencapsulation. Akbari S, Pirbodaghi T, Kamm RD, Hammond PT. Lab Chippubmed:28492663;  doi:10.1039/c6lc01568a

11. Immunogenicity of pulsatile-release PLGA microspheres for single-injection vaccination. Guarecuco R, Lu J, McHugh KJ, Norman JJ, Thapa LS, Lydon E, Langer R, Jaklenec A. Vaccinepubmed:28625520;  doi:10.1016/j.vaccine.2017.05.094

12. Cytosolic delivery of siRNA by ultra-high affinity dsRNA binding proteins. Yang NJ, Kauke MJ, Sun F, Yang LF, Maass KF, Traxlmayr MW, Yu Y, Xu Y, Langer RS, Anderson DG, Wittrup KD. Nucleic Acids Respubmed:28641400;  doi:10.1093/nar/gkx546

13. The promise of organ and tissue preservation to transform medicine. Giwa S, Lewis JK, Alvarez L, Langer R, Roth AE, Church GM, Markmann JF, Sachs DH, Chandraker A, Wertheim JA, Rothblatt M, Boyden ES, Eidbo E, Lee WPA, Pomahac B, Brandacher G, Weinstock DM, Elliott G, Nelson D, Acker JP, Uygun K, Schmalz B, Weegman BP, Tocchio A, Fahy GM, Storey KB, Rubinsky B, Bischof J, Elliott JAW, Woodruff TK, Morris GJ, Demirci U, Brockbank KGM, Woods EJ, Ben RN, Baust JG, Gao D, Fuller B, Rabin Y, Kravitz DC, Taylor MJ, Toner M. Nat Biotechnolpubmed:28591112;  doi:10.1038/nbt.3889

14. Comprehensive proteomic characterization of stem cell-derived extracellular matrices. Ragelle H, Naba A, Larson BL, Zhou F, Prijic M, Whittaker CA, Del Rosario A, Langer R, Hynes RO, Anderson DG. Biomaterialspubmed:28327460;  doi:10.1016/j.biomaterials.2017.03.008

15. Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates. Doloff JC, Veiseh O, Vegas AJ, Tam HH, Farah S, Ma M, Li J, Bader A, Chiu A, Sadraei A, Aresta-Dasilva S, Griffin M, Jhunjhunwala S, Webber M, Siebert S, Tang K, Chen M, Langan E, Dholokia N, Thakrar R, Qi M, Oberholzer J, Greiner DL, Langer R, Anderson DG. Nat Materpubmed:28319612;  doi:10.1038/nmat4866

16. AChiralPentagonalPolyhedralFramework forCharacterizingVirusCapsidStructures. Raguram A, Sasisekharan V, Sasisekharan R. Trends Microbiolpubmed:28094093;  doi:10.1016/j.tim.2016.12.007

17. Open-source, community-driven microfluidics with Metafluidics. Kong DS, Thorsen TA, Babb J, Wick ST, Gam JJ, Weiss R, Carr PA. Nat Biotechnolpubmed:28591125;  doi:10.1038/nbt.3873

18. In vivo genome editing and organoid transplantation models of colorectal cancer and metastasis. Roper J, Tammela T, Cetinbas NM, Akkad A, Roghanian A, Rickelt S, Almeqdadi M, Wu K, Oberli MA, Sanchez-Rivera F, Park YK, Liang X, Eng G, Taylor MS, Azimi R, Kedrin D, Neupane R, Beyaz S, Sicinska ET, Suarez Y, Yoo J, Chen L, Zukerberg L, Katajisto P, Deshpande V, Bass AJ, Tsichlis PN, Lees J, Langer R, Hynes RO, Chen J, Bhutkar A, Jacks T, Yilmaz OH. Nat Biotechnolpubmed:28459449;  doi:10.1038/nbt.3836

19. Ciprofloxacin-nitroxide hybrids with potential for biofilm control. Verderosa AD, de la Fuente-Nunez C, Mansour SC, Cao J, Lu TK, Hancock REW, Fairfull-Smith KE. Eur J Med Chempubmed:28709125;  doi:10.1016/j.ejmech.2017.06.058

20. Next-generation precision antimicrobials: towards personalized treatment of infectious diseases. de la Fuente-Nunez C, Torres MD, Mojica FJ, Lu TK. Curr Opin Microbiolpubmed:28623720;  doi:10.1016/j.mib.2017.05.014

21. Delivery technologies for genome editing. Yin H, Kauffman KJ, Anderson DG. Nat Rev Drug Discovpubmed:28337020;  doi:10.1038/nrd.2016.280

22. Protein Truncating Variants at the Cholesteryl Ester Transfer Protein Gene and Risk for Coronary Heart Disease. Nomura A, Won HH, Khera AV, Takeuchi F, Ito K, McCarthy S, Emdin CA, Klarin D, Natarajan P, Zekavat SM, Gupta N, Peloso GM, Borecki IB, Teslovich TM, Asselta R, Duga S, Merlini PA, Correa A, Kessler T, Wilson JG, Bown MJ, Hall AS, Braund PS, Carey DJ, Murray MF, Kirchner HL, Leader JB, Lavage DR, Manus JN, Hartzel DN, Samani NJ, Schunkert H, Marrugat J, Elosua R, McPherson R, Farrall M, Watkins H, Juang JJ, Hsiung CA, Lin SY, Wang JS, Tada H, Kawashiri MA, Inazu A, Yamagishi M, Katsuya T, Nakashima E, Nakatochi M, Yamamoto K, Yokota M, Momozawa Y, Rotter JI, Lander ES, Rader DJ, Danesh JN, Ardissino D, Gabriel SB, Willer CJ, Abecasis G, Saleheen D, Kubo M, Kato N, Chen YI, Dewey F, Kathiresan S. Circ Respubmed:28506971;  doi:10.1161/CIRCRESAHA.117.311145

23. Improved imputation accuracy of rare and low-frequency variants using population-specific high-coverage WGS-based imputation reference panel. Mitt M, Kals M, Parn K, Gabriel SB, Lander ES, Palotie A, Ripatti S, Morris AP, Metspalu A, Esko T, Magi R, Palta P. Eur J Hum Genetpubmed:28401899;  doi:10.1038/ejhg.2017.51

24. Vesicular stomatitis virus N protein-specific single-domain antibody fragments inhibit replication. Hanke L, Schmidt FI, Knockenhauer KE, Morin B, Whelan SP, Schwartz TU, Ploegh HL. EMBO Reppubmed:28396572;  doi:10.15252/embr.201643764

25. Noninvasive imaging of human immune responses in a human xenograft model of graft-versus-host disease. Van Elssen CH, Rashidian M, Vrbanac V, Wucherpfennig KW, El Habre Z, Sticht J, Freund C, Jacobsen J, Cragnolini J, Ingram J, Plaisier L, Spierings E, Tager AM, Ploegh H. J Nucl Medpubmed:28209904;  doi:10.2967/jnumed.116.186007

26. The long noncoding RNA Wisper controls cardiac fibrosis and remodeling. Micheletti R, Plaisance I, Abraham BJ, Sarre A, Ting CC, Alexanian M, Maric D, Maison D, Nemir M, Young RA, Schroen B, Gonzalez A, Ounzain S, Pedrazzini T. Sci Transl Medpubmed:28637928;  doi:10.1126/scitranslmed.aai9118

27. Activation of the LMO2 oncogene through a somatically acquired neomorphic promoter in T-cell acute lymphoblastic leukemia. Rahman S, Magnussen M, Leon TE, Farah N, Li Z, Abraham BJ, Alapi KZ, Mitchell RJ, Naughton T, Fielding AK, Pizzey A, Bustraan S, Allen C, Popa T, Pike-Overzet K, Garcia-Perez L, Gale RE, Linch DC, Staal FJ, Young RA, Look AT, Mansour MR. Bloodpubmed:28270453;  doi:10.1182/blood-2016-09-742148

28. The Super-Enhancer-Derived alncRNA-EC7/Bloodlinc Potentiates Red Blood Cell Development in trans. Alvarez-Dominguez JR, Knoll M, Gromatzky AA, Lodish HF. Cell Reppubmed:28636939;  doi:10.1016/j.celrep.2017.05.082

29. An Integrative Framework Reveals Signaling-to-Transcription Events in Toll-like Receptor Signaling. Mertins P, Przybylski D, Yosef N, Qiao J, Clauser K, Raychowdhury R, Eisenhaure TM, Maritzen T, Haucke V, Satoh T, Akira S, Carr SA, Regev A, Hacohen N, Chevrier N. Cell Reppubmed:28658630;  doi:10.1016/j.celrep.2017.06.016

30. Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms. Rusu V, Hoch E, Mercader JM, Tenen DE, Gymrek M, Hartigan CR, DeRan M, von Grotthuss M, Fontanillas P, Spooner A, Guzman G, Deik AA, Pierce KA, Dennis C, Clish CB, Carr SA, Wagner BK, Schenone M, Ng MCY, Chen BH, Centeno-Cruz F, Zerrweck C, Orozco L, Altshuler DM, Schreiber SL, Florez JC, Jacobs SBR, Lander ES. Cellpubmed:28666119;  doi:10.1016/j.cell.2017.06.011

31. IFNgamma-Dependent Tissue-Immune Homeostasis Is Co-opted in the Tumor Microenvironment. Nirschl CJ, Suarez-Farinas M, Izar B, Prakadan S, Dannenfelser R, Tirosh I, Liu Y, Zhu Q, Devi KSP, Carroll SL, Chau D, Rezaee M, Kim TG, Huang R, Fuentes-Duculan J, Song-Zhao GX, Gulati N, Lowes MA, King SL, Quintana FJ, Lee YS, Krueger JG, Sarin KY, Yoon CH, Garraway L, Regev A, Shalek AK, Troyanskaya O, Anandasabapathy N. Cellpubmed:28666115;  doi:10.1016/j.cell.2017.06.016

32. Chromosome Mis-segregation Generates Cell-Cycle-Arrested Cells with Complex Karyotypes that Are Eliminated by the Immune System. Santaguida S, Richardson A, Iyer DR, M'Saad O, Zasadil L, Knouse KA, Wong YL, Rhind N, Desai A, Amon A. Dev Cellpubmed:28633018;  doi:10.1016/j.devcel.2017.05.022

33. Germinal Center Selection and Affinity Maturation Require Dynamic Regulation of mTORC1 Kinase. Ersching J, Efeyan A, Mesin L, Jacobsen JT, Pasqual G, Grabiner BC, Dominguez-Sola D, Sabatini DM, Victora GD. Immunitypubmed:28636954;  doi:10.1016/j.immuni.2017.06.005

34. Nature and Nurture: What Determines Tumor Metabolic Phenotypes?. Mayers JR, Vander Heiden MG. Cancer Respubmed:28584183;  doi:10.1158/0008-5472.CAN-17-0165

35. Pyruvate kinase inhibits proliferation during postnatal cerebellar neurogenesis and suppresses medulloblastoma formation. Tech K, Tikunov AP, Farooq H, Morrissy AS, Meidinger J, Fish T, Green SC, Liu H, Li Y, Mungall AJ, Moore RA, Ma Y, Jones SJ, Marra MA, Vander Heiden MG, Taylor MD, MacDonald J, Gershon TR. Cancer Respubmed:28515149;  doi:10.1158/0008-5472.CAN-16-3304

36. Pyruvate kinase M2 activation may protect against the progression of diabetic glomerular pathology and mitochondrial dysfunction. Qi W, Keenan HA, Li Q, Ishikado A, Kannt A, Sadowski T, Yorek MA, Wu IH, Lockhart S, Coppey LJ, Pfenninger A, Liew CW, Qiang G, Burkart AM, Hastings S, Pober D, Cahill C, Niewczas MA, Israelsen WJ, Tinsley L, Stillman IE, Amenta PS, Feener EP, Vander Heiden MG, Stanton RC, King GL. Nat Medpubmed:28436957;  doi:10.1038/nm.4328

37. Mex3a Marks a Slowly Dividing Subpopulation of Lgr5+ Intestinal Stem Cells. Barriga FM, Montagni E, Mana M, Mendez-Lago M, Hernando-Momblona X, Sevillano M, Guillaumet-Adkins A, Rodriguez-Esteban G, Buczacki SJ, Gut M, Heyn H, Winton DJ, Yilmaz OH, Attolini CS, Gut I, Batlle E. Cell Stem Cellpubmed:28285904;  doi:10.1016/j.stem.2017.02.007

38. Endothelium-derived fibronectin regulates neonatal vascular morphogenesis in an autocrine fashion. Turner CJ, Badu-Nkansah K, Hynes RO. Angiogenesispubmed:28667352;  doi:10.1007/s10456-017-9563-8

39. Mechanisms of DNA damage, repair, and mutagenesis. Chatterjee N, Walker GC. Environ Mol Mutagenpubmed:28485537;  doi:10.1002/em.22087