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: August 2016

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1. 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 Engl. pubmed:27554600;  doi:10.1002/anie.201606123

2. Injectable and glucose-responsive hydrogels based on boronic acid-glucose complexation. Dong Y, Wang W, Veiseh O, Appel EA, Xue K, Webber MJ, Tang B, Yang XW, Weir G, Langer R, Anderson DG. Langmuir. pubmed:27455412;  doi:10.1021/acs.langmuir.5b04755

3. Anatomical and procedural determinants of catheter-based renal denervation. Ewen S, Ukena C, Luscher TF, Bergmann M, Blankestijn PJ, Blessing E, Cremers B, Dorr O, Hering D, Kaiser L, Nef H, Noory E, Schlaich M, Sharif F, Sudano I, Vogel B, Voskuil M, Zeller T, Tzafriri AR, Edelman ER, Lauder L, Scheller B, Bohm M, Mahfoud F. Cardiovasc Revasc Med. pubmed:27617388;  doi:10.1016/j.carrev.2016.08.004

4. 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 Cell. pubmed:27559126;  doi:10.1091/mbc.E16-04-0212

5. Identification of polymer surface adsorbed proteins implicated in pluripotent human embryonic stem cell expansion. Hammad M, Rao W, Smith JG, Anderson DG, Langer R, Young LE, Barrett DA, Davies MC, Denning C, Alexander MR. Biomater Sci. pubmed:27466628;  doi:10.1039/c6bm00214e

6. Splenic progenitors aid in maintaining high neutrophil numbers at sites of sterile chronic inflammation. Jhunjhunwala S, Alvarez D, Aresta-DaSilva S, Tang K, Tang BC, Greiner DL, Newburger PE, von Andrian UH, Langer R, Anderson DG. J Leukoc Biol. pubmed:26965635;  doi:10.1189/jlb.1HI0615-248RR

7. Synchronized cycles of bacterial lysis for in vivo delivery. Din MO, Danino T, Prindle A, Skalak M, Selimkhanov J, Allen K, Julio E, Atolia E, Tsimring LS, Bhatia SN, Hasty J. Nature. pubmed:27437587;  doi:10.1038/nature18930

8. Sequence-Defined Oligomers from Hydroxyproline Building Blocks for Parallel Synthesis Applications. Kanasty RL, Vegas AJ, Ceo LM, Maier M, Charisse K, Nair JK, Langer R, Anderson DG. Angew Chem Int Ed Engl. pubmed:27365192;  doi:10.1002/anie.201602748

9. Spatial Control of Gene Expression by Nanocarriers Using Heparin Masking and Ultrasound-Targeted Microbubble Destruction. Chertok B, Langer R, Anderson DG. ACS Nano. pubmed:27472268;  doi:10.1021/acsnano.6b01199

10. Neuron-Targeted Nanoparticle for siRNA Delivery to Traumatic Brain Injuries. Kwon EJ, Skalak M, Lo Bu R, Bhatia SN. ACS Nano. pubmed:27429164;  doi:10.1021/acsnano.6b03858

11. Base Excision Repair of N6-Deoxyadenosine Adducts of 1,3-Butadiene. Wickramaratne SS, Banda D, Ji S, Manlove AH, Malayappan B, Nunez NN, Samson LD, Campbell C, David SS, Tretyakova NY. Biochemistry. pubmed:27552084;  doi:10.1021/acs.biochem.6b00553

12. 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 Pharmacol. pubmed:27567007;  doi:10.1002/psp4.12104

13. Core-Shell Composite Hydrogels for Controlled Nanocrystal Formation and Release of Hydrophobic Active Pharmaceutical Ingredients. Badruddoza AZ, Godfrin PD, Myerson AS, Trout BL, Doyle PS. Adv Healthc Mater. pubmed:27249402;  doi:10.1002/adhm.201600266

14. An elastic second skin. Yu B, Kang SY, Akthakul A, Ramadurai N, Pilkenton M, Patel A, Nashat A, Anderson DG, Sakamoto FH, Gilchrest BA, Anderson RR, Langer R. Nat Mater. pubmed:27159017;  doi:10.1038/nmat4635

15. Magnetic Multivalent Trehalose Glycopolymer Nanoparticles for the Detection of Mycobacteria. Chen X, Wu B, Jayawardana KW, Hao N, Jayawardena HS, Langer R, Jaklenec A, Yan M. Adv Healthc Mater. pubmed:27283385;  doi:10.1002/adhm.201600071

16. Strong Enrichment of Aromatic Residues in Binding Sites from a Charge-Neutralized Hyperthermostable Sso7d Scaffold Library. Traxlmayr MW, Kiefer JD, Srinivas RR, Lobner E, Tisdale AW, Mehta NK, Yang NJ, Tidor B, Wittrup KD. J Biol Chem. pubmed:27582495;  doi:10.1074/jbc.M116.741314

17. Circumferential optical coherence tomography angiography imaging of the swine esophagus using a micromotor balloon catheter. Lee HC, Ahsen OO, Liang K, Wang Z, Cleveland C, Booth L, Potsaid B, Jayaraman V, Cable AE, Mashimo H, Langer R, Traverso G, Fujimoto JG. Biomed Opt Express. pubmed:27570688;  doi:10.1364/BOE.7.002927

18. 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 Cell. pubmed:27618485;  doi:10.1016/j.molcel.2016.08.010

19. Deletion of DXZ4 on the human inactive X chromosome alters higher-order genome architecture. Darrow EM, Huntley MH, Dudchenko O, Stamenova EK, Durand NC, Sun Z, Huang SC, Sanborn AL, Machol I, Shamim M, Seberg AP, Lander ES, Chadwick BP, Aiden EL. Proc Natl Acad Sci U S A. pubmed:27432957;  doi:10.1073/pnas.1609643113

20. Microfluidic device for the formation of optically excitable, three-dimensional, compartmentalized motor units. Uzel SG, Platt RJ, Subramanian V, Pearl TM, Rowlands CJ, Chan V, Boyer LA, So PT, Kamm RD. Sci Adv. pubmed:27493991;  doi:10.1126/sciadv.1501429

21. The genetic architecture of type 2 diabetes. Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, Ma C, Fontanillas P, Moutsianas L, McCarthy DJ, Rivas MA, Perry JR, Sim X, Blackwell TW, Robertson NR, Rayner NW, Cingolani P, Locke AE, Tajes JF, Highland HM, Dupuis J, Chines PS, Lindgren CM, Hartl C, Jackson AU, Chen H, Huyghe JR, van de Bunt M, Pearson RD, Kumar A, Muller-Nurasyid M, Grarup N, Stringham HM, Gamazon ER, Lee J, Chen Y, Scott RA, Below JE, Chen P, Huang J, Go MJ, Stitzel ML, Pasko D, Parker SC, Varga TV, Green T, Beer NL, Day-Williams AG, Ferreira T, Fingerlin T, Horikoshi M, Hu C, Huh I, Ikram MK, Kim BJ, Kim Y, Kim YJ, Kwon MS, Lee J, Lee S, Lin KH, Maxwell TJ, Nagai Y, Wang X, Welch RP, Yoon J, Zhang W, Barzilai N, Voight BF, Han BG, Jenkinson CP, Kuulasmaa T, Kuusisto J, Manning A, Ng MC, Palmer ND, Balkau B, Stancakova A, Abboud HE, Boeing H, Giedraitis V, Prabhakaran D, Gottesman O, Scott J, Carey J, Kwan P, Grant G, Smith JD, Neale BM, Purcell S, Butterworth AS, Howson JM, Lee HM, Lu Y, Kwak SH, Zhao W, Danesh J, Lam VK, Park KS, Saleheen D, So WY, Tam CH, Afzal U, Aguilar D, Arya R, Aung T, Chan E, Navarro C, Cheng CY, Palli D, Correa A, Curran JE, Rybin D, Farook VS, Fowler SP, Freedman BI, Griswold M, Hale DE, Hicks PJ, Khor CC, Kumar S, Lehne B, Thuillier D, Lim WY, Liu J, van der Schouw YT, Loh M, Musani SK, Puppala S, Scott WR, Yengo L, Tan ST, Taylor HAJr, Thameem F, Wilson G, Wong TY, Njolstad PR, Levy JC, Mangino M, Bonnycastle LL, Schwarzmayr T, Fadista J, Surdulescu GL, Herder C, Groves CJ, Wieland T, Bork-Jensen J, Brandslund I, Christensen C, Koistinen HA, Doney AS, Kinnunen L, Esko T, Farmer AJ, Hakaste L, Hodgkiss D, Kravic J, Lyssenko V, Hollensted M, Jorgensen ME, Jorgensen T, Ladenvall C, Justesen JM, Karajamaki A, Kriebel J, Rathmann W, Lannfelt L, Lauritzen T, Narisu N, Linneberg A, Melander O, Milani L, Neville M, Orho-Melander M, Qi L, Qi Q, Roden M, Rolandsson O, Swift A, Rosengren AH, Stirrups K, Wood AR, Mihailov E, Blancher C, Carneiro MO, Maguire J, Poplin R, Shakir K, Fennell T, DePristo M, Hrabe de Angelis M, Deloukas P, Gjesing AP, Jun G, Nilsson P, Murphy J, Onofrio R, Thorand B, Hansen T, Meisinger C, Hu FB, Isomaa B, Karpe F, Liang L, Peters A, Huth C, O'Rahilly SP, Palmer CN, Pedersen O, Rauramaa R, Tuomilehto J, Salomaa V, Watanabe RM, Syvanen AC, Bergman RN, Bharadwaj D, Bottinger EP, Cho YS, Chandak GR, Chan JC, Chia KS, Daly MJ, Ebrahim SB, Langenberg C, Elliott P, Jablonski KA, Lehman DM, Jia W, Ma RC, Pollin TI, Sandhu M, Tandon N, Froguel P, Barroso I, Teo YY, Zeggini E, Loos RJ, Small KS, Ried JS, DeFronzo RA, Grallert H, Glaser B, Metspalu A, Wareham NJ, Walker M, Banks E, Gieger C, Ingelsson E, Im HK, Illig T, Franks PW, Buck G, Trakalo J, Buck D, Prokopenko I, Magi R, Lind L, Farjoun Y, Owen KR, Gloyn AL, Strauch K, Tuomi T, Kooner JS, Lee JY, Park T, Donnelly P, Morris AD, Hattersley AT, Bowden DW, Collins FS, Atzmon G, Chambers JC, Spector TD, Laakso M, Strom TM, Bell GI, Blangero J, Duggirala R, Tai ES, McVean G, Hanis CL, Wilson JG, Seielstad M, Frayling TM, Meigs JB, Cox NJ, Sladek R, Lander ES, Gabriel S, Burtt NP, Mohlke KL, Meitinger T, Groop L, Abecasis G, Florez JC, Scott LJ, Morris AP, Kang HM, Boehnke M, Altshuler D, McCarthy MI. Nature. pubmed:27398621;  doi:10.1038/nature18642

22. The rate of protein synthesis in hematopoietic stem cells is limited partly by 4E-BPs. Signer RA, Qi L, Zhao Z, Thompson D, Sigova AA, Fan ZP, DeMartino GN, Young RA, Sonenberg N, Morrison SJ. Genes Dev. pubmed:27492367;  doi:10.1101/gad.282756.116

23. Parallel evolution of male germline epigenetic poising and somatic development in animals. Lesch BJ, Silber SJ, McCarrey JR, Page DC. Nat Genet. pubmed:27294618;  doi:10.1038/ng.3591

24. Div-Seq: Single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons. Habib N, Li Y, Heidenreich M, Swiech L, Avraham-Davidi I, Trombetta JJ, Hession C, Zhang F, Regev A. Science. pubmed:27471252;  doi:10.1126/science.aad7038

25. C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. Abudayyeh OO, Gootenberg JS, Konermann S, Joung J, Slaymaker IM, Cox DB, Shmakov S, Makarova KS, Semenova E, Minakhin L, Severinov K, Regev A, Lander ES, Koonin EV, Zhang F. Science. pubmed:27256883;  doi:10.1126/science.aaf5573

26. Cell-Type-Specific Alternative Splicing Governs Cell Fate in the Developing Cerebral Cortex. Zhang X, Chen MH, Wu X, Kodani A, Fan J, Doan R, Ozawa M, Ma J, Yoshida N, Reiter JF, Black DL, Kharchenko PV, Sharp PA, Walsh CA. Cell. pubmed:27565344;  doi:10.1016/j.cell.2016.07.025

27. Comprehensive Classification of Retinal Bipolar Neurons by Single-Cell Transcriptomics. Shekhar K, Lapan SW, Whitney IE, Tran NM, Macosko EZ, Kowalczyk M, Adiconis X, Levin JZ, Nemesh J, Goldman M, McCarroll SA, Cepko CL, Regev A, Sanes JR. Cell. pubmed:27565351;  doi:10.1016/j.cell.2016.07.054

28. Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83. von Rohrscheidt J, Petrozziello E, Nedjic J, Federle C, Krzyzak L, Ploegh HL, Ishido S, Steinkasserer A, Klein L. J Exp Med. pubmed:27503071;  doi:10.1084/jem.20160316

29. 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

30. 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 Genet. pubmed:27548314;  doi:10.1038/ng.3651

31. The importance of serine metabolism in cancer. Mattaini KR, Sullivan MR, Vander Heiden MG. J Cell Biol. pubmed:27458133;  doi:10.1083/jcb.201604085

32. Association between very small tumor size and increased cancer-specific mortality following radical prostatectomy in node-positive prostate cancer. Muralidhar V, Mahal BA, Nezolosky MD, Beard CJ, Feng FY, Martin NE, Efstathiou JA, Choueiri TK, Pomerantz MM, Sweeney CJ, Trinh QD, Vander Heiden MG, Nguyen PL. BJU Int. pubmed:26235660;  doi:10.1111/bju.13248

33. A Fungal-Selective Cytochrome bc1 Inhibitor Impairs Virulence and Prevents the Evolution of Drug Resistance. Vincent BM, Langlois JB, Srinivas R, Lancaster AK, Scherz-Shouval R, Whitesell L, Tidor B, Buchwald SL, Lindquist S. Cell Chem Biol. pubmed:27524297;  doi:10.1016/j.chembiol.2016.06.016

34. Aging and Rejuvenation: Insights from Rusty Gage, Leonard Guarente, and Amy Wagers. Gage FH, Guarente LP, Wagers AJ. Trends Mol Med. pubmed:27396512;  doi:10.1016/j.molmed.2016.06.011

35. Mule Regulates the Intestinal Stem Cell Niche via the Wnt Pathway and Targets EphB3 for Proteasomal and Lysosomal Degradation. Dominguez-Brauer C, Hao Z, Elia AJ, Fortin JM, Nechanitzky R, Brauer PM, Sheng Y, Mana MD, Chio II, Haight J, Pollett A, Cairns R, Tworzyanski L, Inoue S, Reardon C, Marques A, Silvester J, Cox MA, Wakeham A, Yilmaz OH, Sabatini DM, van Es JH, Clevers H, Sato T, Mak TW. Cell Stem Cell. pubmed:27184401;  doi:10.1016/j.stem.2016.04.002

36. Mechanism of arginine sensing by CASTOR1 upstream of mTORC1. Saxton RA, Chantranupong L, Knockenhauer KE, Schwartz TU, Sabatini DM. Nature. pubmed:27487210;  doi:10.1038/nature19079

37. Absolute Quantification of Matrix Metabolites Reveals the Dynamics of Mitochondrial Metabolism. Chen WW, Freinkman E, Wang T, Birsoy K, Sabatini DM. Cell. pubmed:27565352;  doi:10.1016/j.cell.2016.07.040

38. The unexpected role of mTORC1 in intestinal stem cells during calorie restriction. Igarashi M, Guarente L. Cell Cycle. pubmed:27592731;  doi:10.1080/15384101.2016.1221210

39. Circadian Rhythm Disruption Promotes Lung Tumorigenesis. Papagiannakopoulos T, Bauer MR, Davidson SM, Heimann M, Subbaraj L, Bhutkar A, Bartlebaugh J, Vander Heiden MG, Jacks T. Cell Metab. pubmed:27476975;  doi:10.1016/j.cmet.2016.07.001

40. Inflammation triggers Zeb1-dependent escape from tumor latency. De Cock JM, Shibue T, Dongre A, Keckesova Z, Reinhardt F, Weinberg RA. Cancer Res. pubmed:27530323;  doi:10.1158/0008-5472.CAN-16-0608

41. A senescence secretory switch mediated by PI3K/AKT/mTOR activation controls chemoprotective endothelial secretory responses. Bent EH, Gilbert LA, Hemann MT. Genes Dev. pubmed:27566778;  doi:10.1101/gad.284851.116

42. 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 Soc. pubmed:27570149;  doi:10.1021/jacs.6b06937

43. Proteomic Analysis of Unbounded Cellular Compartments: Synaptic Clefts. Loh KH, Stawski PS, Draycott AS, Udeshi ND, Lehrman EK, Wilton DK, Svinkina T, Deerinck TJ, Ellisman MH, Stevens B, Carr SA, Ting AY. Cell. pubmed:27565350;  doi:10.1016/j.cell.2016.07.041