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: March 2018

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1. Genetic mechanisms of immune evasion in colorectal cancer. Grasso CS, Giannakis M, Wells DK, Hamada T, Mu XJ, Quist M, Nowak JA, Nishihara R, Qian ZR, Inamura K, Morikawa T, Nosho K, Abril-Rodriguez G, Connolly C, Escuin-Ordinas H, Geybels MS, Grady WM, Hsu L, Hu-Lieskovan S, Huyghe JR, Kim YJ, Krystofinski PE, Leiserson MD, Montoya DJ, Nadel BB, Pellegrini M, Pritchard CC, Puig-Saus C, Quist EH, Raphael BJ, Salipante SJ, Shin DS, Shinbrot E, Shirts B, Shukla S, Stanford JL, Sun W, Tsoi J, Upfill-Brown A, Wheeler DA, Wu CJ, Yu M, Zaidi SH, Zaretsky JM, Gabriel SB, Lander ES, Garraway LA, Hudson TJ, Fuchs CS, Ribas A, Ogino S, Peters U. Cancer Discovpubmed:29510987;  doi:10.1158/2159-8290.CD-17-1327

2. Impairment of an Endothelial NAD(+)-H2S Signaling Network Is a Reversible Cause of Vascular Aging. Das A, Huang GX, Bonkowski MS, Longchamp A, Li C, Schultz MB, Kim LJ, Osborne B, Joshi S, Lu Y, Trevino-Villarreal JH, Kang MJ, Hung TT, Lee B, Williams EO, Igarashi M, Mitchell JR, Wu LE, Turner N, Arany Z, Guarente L, Sinclair DA. Cellpubmed:29570999;  doi:10.1016/j.cell.2018.02.008

3. BCL11B Drives Human Mammary Stem Cell Self-Renewal In Vitro by Inhibiting Basal Differentiation. Miller DH, Jin DX, Sokol ES, Cabrera JR, Superville DA, Gorelov RA, Kuperwasser C, Gupta PB. Stem Cell Reportspubmed:29503088;  doi:10.1016/j.stemcr.2018.01.036

4. Matched Developmental Timing of Donor Cells with the Host Is Crucial for Chimera Formation. Cohen MA, Markoulaki S, Jaenisch R. Stem Cell Reportspubmed:29606614;  doi:10.1016/j.stemcr.2018.03.004

5. c-MYC drives a subset of high-risk pediatric neuroblastomas and is activated through mechanisms including enhancer hijacking and focal enhancer amplification. Zimmerman MW, Liu Y, He S, Durbin AD, Abraham BJ, Easton J, Shao Y, Xu B, Zhu S, Zhang X, Li Z, Weichert-Leahey N, Young RA, Zhang J, Look AT. Cancer Discovpubmed:29284669;  doi:10.1158/2159-8290.CD-17-0993

6. Exploiting an Asp-Glu "switch" in glycogen synthase kinase 3 to design paralog-selective inhibitors for use in acute myeloid leukemia. Wagner FF, Benajiba L, Campbell AJ, Weiwer M, Sacher JR, Gale JP, Ross L, Puissant A, Alexe G, Conway A, Back M, Pikman Y, Galinsky I, DeAngelo DJ, Stone RM, Kaya T, Shi X, Robers MB, Machleidt T, Wilkinson J, Hermine O, Kung A, Stein AJ, Lakshminarasimhan D, Hemann MT, Scolnick E, Zhang YL, Pan JQ, Stegmaier K, Holson EB. Sci Transl Medpubmed:29515000;  doi:10.1126/scitranslmed.aam8460

7. Uveal melanoma driver mutations in GNAQ/11 yield numerous changes in melanocyte biology. Perez DE, Henle AM, Amsterdam A, Hagen HR, Lees JA. Pigment Cell Melanoma Respubmed:29570931;  doi:10.1111/pcmr.12700

8. The Role of HSP90 in the Regulation of de novo Purine Biosynthesis. Pedley AM, Karras GI, Zhang X, Lindquist SL, Benkovic SJ. Biochemistrypubmed:29553718;  doi:10.1021/acs.biochem.8b00140

9. Yeast can accommodate phosphotyrosine: v-Src toxicity in yeast arises from a single disrupted pathway. Kritzer JA, Freyzon Y, Lindquist S. FEMS Yeast Respubmed:29546391;  doi:10.1093/femsyr/foy027

10. Translocon Declogger Ste24 Protects against IAPP Oligomer-Induced Proteotoxicity. Kayatekin C, Amasino A, Gaglia G, Flannick J, Bonner JM, Fanning S, Narayan P, Barrasa MI, Pincus D, Landgraf D, Nelson J, Hesse WR, Costanzo M, Myers CL, Boone C, Florez JC, Lindquist S. Cellpubmed:29526462;  doi:10.1016/j.cell.2018.02.026

11. A mouse model of DEPDC5-related epilepsy: Neuronal loss of Depdc5 causes dysplastic and ectopic neurons, increased mTOR signaling, and seizure susceptibility. Yuskaitis CJ, Jones BM, Wolfson RL, Super CE, Dhamne SC, Rotenberg A, Sabatini DM, Sahin M, Poduri A. Neurobiol Dispubmed:29274432;  doi:10.1016/j.nbd.2017.12.010

12. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, Annicchiarico-Petruzzelli M, Antonov AV, Arama E, Baehrecke EH, Barlev NA, Bazan NG, Bernassola F, Bertrand MJM, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Boya P, Brenner C, Campanella M, Candi E, Carmona-Gutierrez D, Cecconi F, Chan FK, Chandel NS, Cheng EH, Chipuk JE, Cidlowski JA, Ciechanover A, Cohen GM, Conrad M, Cubillos-Ruiz JR, Czabotar PE, D'Angiolella V, Dawson TM, Dawson VL, De Laurenzi V, De Maria R, Debatin KM, DeBerardinis RJ, Deshmukh M, Di Daniele N, Di Virgilio F, Dixit VM, Dixon SJ, Duckett CS, Dynlacht BD, El-Deiry WS, Elrod JW, Fimia GM, Fulda S, Garcia-Saez AJ, Garg AD, Garrido C, Gavathiotis E, Golstein P, Gottlieb E, Green DR, Greene LA, Gronemeyer H, Gross A, Hajnoczky G, Hardwick JM, Harris IS, Hengartner MO, Hetz C, Ichijo H, Jaattela M, Joseph B, Jost PJ, Juin PP, Kaiser WJ, Karin M, Kaufmann T, Kepp O, Kimchi A, Kitsis RN, Klionsky DJ, Knight RA, Kumar S, Lee SW, Lemasters JJ, Levine B, Linkermann A, Lipton SA, Lockshin RA, Lopez-Otin C, Lowe SW, Luedde T, Lugli E, MacFarlane M, Madeo F, Malewicz M, Malorni W, Manic G, Marine JC, Martin SJ, Martinou JC, Medema JP, Mehlen P, Meier P, Melino S, Miao EA, Molkentin JD, Moll UM, Munoz-Pinedo C, Nagata S, Nunez G, Oberst A, Oren M, Overholtzer M, Pagano M, Panaretakis T, Pasparakis M, Penninger JM, Pereira DM, Pervaiz S, Peter ME, Piacentini M, Pinton P, Prehn JHM, Puthalakath H, Rabinovich GA, Rehm M, Rizzuto R, Rodrigues CMP, Rubinsztein DC, Rudel T, Ryan KM, Sayan E, Scorrano L, Shao F, Shi Y, Silke J, Simon HU, Sistigu A, Stockwell BR, Strasser A, Szabadkai G, Tait SWG, Tang D, Tavernarakis N, Thorburn A, Tsujimoto Y, Turk B, Vanden Berghe T, Vandenabeele P, Vander Heiden MG, Villunger A, Virgin HW, Vousden KH, Vucic D, Wagner EF, Walczak H, Wallach D, Wang Y, Wells JA, Wood W, Yuan J, Zakeri Z, Zhivotovsky B, Zitvogel L, Melino G, Kroemer G. Cell Death Differpubmed:29362479;  doi:10.1038/s41418-017-0012-4

13. TAZ/WWTR1 mediates the pulmonary effects of NKX2-1 mutations in Brain-Lung-Thyroid syndrome. Moya CM, Zaballos MA, Garzon L, Luna C, Simon R, Yaffe MB, Gallego E, Santisteban P, Moreno JC. J Clin Endocrinol Metabpubmed:29294041;  doi:10.1210/jc.2017-01241

14. Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies. Edington CD, Chen WLK, Geishecker E, Kassis T, Soenksen LR, Bhushan BM, Freake D, Kirschner J, Maass C, Tsamandouras N, Valdez J, Cook CD, Parent T, Snyder S, Yu J, Suter E, Shockley M, Velazquez J, Velazquez JJ, Stockdale L, Papps JP, Lee I, Vann N, Gamboa M, LaBarge ME, Zhong Z, Wang X, Boyer LA, Lauffenburger DA, Carrier RL, Communal C, Tannenbaum SR, Stokes CL, Hughes DJ, Rohatgi G, Trumper DL, Cirit M, Griffith LG. Sci Reppubmed:29540740;  doi:10.1038/s41598-018-22749-0

15. From 3D Organoids back to 2D Enteroids. Braverman J, Yilmaz OH. Dev Cellpubmed:29533766;  doi:10.1016/j.devcel.2018.02.016

16. Fas Promotes T Helper 17 Cell Differentiation and Inhibits T Helper 1 Cell Development by Binding and Sequestering Transcription Factor STAT1. Meyer Zu Horste G, Przybylski D, Schramm MA, Wang C, Schnell A, Lee Y, Sobel R, Regev A, Kuchroo VK. Immunitypubmed:29562202;  doi:10.1016/j.immuni.2018.03.008

17. Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis. Khajuria RK, Munschauer M, Ulirsch JC, Fiorini C, Ludwig LS, McFarland SK, Abdulhay NJ, Specht H, Keshishian H, Mani DR, Jovanovic M, Ellis SR, Fulco CP, Engreitz JM, Schutz S, Lian J, Gripp KW, Weinberg OK, Pinkus GS, Gehrke L, Regev A, Lander ES, Gazda HT, Lee WY, Panse VG, Carr SA, Sankaran VG. Cellpubmed:29551269;  doi:10.1016/j.cell.2018.02.036

18. Impact of oncogenic pathways on evasion of antitumour immune responses. Spranger S, Gajewski TF. Nat Rev Cancerpubmed:29326431;  doi:10.1038/nrc.2017.117

19. The effect of geometric isomerism on the anticancer activity of the monofunctional platinum complex trans-[Pt(NH3)2(phenanthridine)Cl]NO3. Zhou W, Almeqdadi M, Xifaras ME, Riddell IA, Yilmaz OH, Lippard SJ. Chem Commun (Camb)pubmed:29484327;  doi:10.1039/c8cc00393a

20. Site-Selective Cysteine-Cyclooctyne Conjugation. Zhang C, Dai P, Vinogradov AA, Gates ZP, Pentelute BL. Angew Chem Int Ed Englpubmed:29575377;  doi:10.1002/anie.201800860

21. Discovery of a 29-amino-acid reactive abiotic peptide for selective cysteine arylation. Evans ED, Pentelute BL. ACS Chem Biolpubmed:29283243;  doi:10.1021/acschembio.7b00520

22. High-Risk Breast Lesions: A Machine Learning Model to Predict Pathologic Upgrade and Reduce Unnecessary Surgical Excision. Bahl M, Barzilay R, Yedidia AB, Locascio NJ, Yu L, Lehman CD. Radiologypubmed:29039725;  doi:10.1148/radiol.2017170549

23. Inflammatory but not mitogenic contexts prime synovial fibroblasts for compensatory signaling responses to p38 inhibition. Jones DS, Jenney AP, Joughin BA, Sorger PK, Lauffenburger DA. Sci Signalpubmed:29511118;  doi:10.1126/scisignal.aal1601

24. The colonic epithelium plays an active role in promoting colitis by shaping the tissue cytokine profile. Lyons J, Ghazi PC, Starchenko A, Tovaglieri A, Baldwin KR, Poulin EJ, Gierut JJ, Genetti C, Yajnik V, Breault DT, Lauffenburger DA, Haigis KM. PLoS Biolpubmed:29596476;  doi:10.1371/journal.pbio.2002417

25. Identifying and Targeting Sporadic Oncogenic Genetic Aberrations in Mouse Models of Triple Negative Breast Cancer. Liu H, Murphy CJ, Karreth FA, Emdal KB, White FM, Elemento O, Toker A, Wulf GM, Cantley LC. Cancer Discovpubmed:29203461;  doi:10.1158/2159-8290.CD-17-0679

26. Polymeric endovascular strut and lumen detection algorithm for intracoronary optical coherence tomography images. Amrute JM, Athanasiou LS, Rikhtegar F, de la Torre Hernandez JM, Camarero TG, Edelman ER. J Biomed Optpubmed:29560624;  doi:10.1117/1.JBO.23.3.036010

27. Anatomical and procedural determinants of ambulatory blood pressure lowering following catheter-based renal denervation using radiofrequency. Lauder L, Ewen S, Tzafriri AR, Edelman ER, Cremers B, Kulenthiran S, Ukena C, Linz D, Kindermann I, Tsioufis C, Scheller B, Bohm M, Mahfoud F. Cardiovasc Revasc Medpubmed:29555535;  doi:10.1016/j.carrev.2018.02.016

28. Vascular Tissue Engineering: Progress, Challenges, and Clinical Promise. Song HG, Rumma RT, Ozaki CK, Edelman ER, Chen CS. Cell Stem Cellpubmed:29499152;  doi:10.1016/j.stem.2018.02.009

29. Strain-induced accelerated asymmetric spatial degradation of polymeric vascular scaffolds. Wang PJ, Ferralis N, Conway C, Grossman JC, Edelman ER. Proc Natl Acad Sci U S Apubmed:29483243;  doi:10.1073/pnas.1716420115

30. Defining drug and target protein distributions after stent-based drug release: Durable versus deployable coatings. Tzafriri AR, Garcia-Polite F, Li X, Keating J, Balaguer JM, Zani B, Bailey L, Markham P, Kiorpes TC, Carlyle W, Edelman ER. J Control Releasepubmed:29421608;  doi:10.1016/j.jconrel.2018.02.007

31. Structurally modulated codelivery of siRNA and Argonaute 2 for enhanced RNA interference. Li J, Wu C, Wang W, He Y, Elkayam E, Joshua-Tor L, Hammond PT. Proc Natl Acad Sci U S Apubmed:29432194;  doi:10.1073/pnas.1719565115

32. Surface tension-assisted additive manufacturing. Ragelle H, Tibbitt MW, Wu SY, Castillo MA, Cheng GZ, Gangadharan SP, Anderson DG, Cima MJ, Langer R. Nat Communpubmed:29567939;  doi:10.1038/s41467-018-03391-w

33. Rapid, Single-Cell Analysis and Discovery of Vectored mRNA Transfection In Vivo with a loxP-Flanked tdTomato Reporter Mouse. Kauffman KJ, Oberli MA, Dorkin JR, Hurtado JE, Kaczmarek JC, Bhadani S, Wyckoff J, Langer R, Jaklenec A, Anderson DG. Mol Ther Nucleic Acidspubmed:29499956;  doi:10.1016/j.omtn.2017.11.005

34. Partial DNA-guided Cas9 enables genome editing with reduced off-target activity. Yin H, Song CQ, Suresh S, Kwan SY, Wu Q, Walsh S, Ding J, Bogorad RL, Zhu LJ, Wolfe SA, Koteliansky V, Xue W, Langer R, Anderson DG. Nat Chem Biolpubmed:29377001;  doi:10.1038/nchembio.2559

35. Yeast-Based Synthetic Biology Platform for Antimicrobial Peptide Production. Cao J, de la Fuente-Nunez C, Ou RW, Torres MT, Pande SG, Sinskey AJ, Lu TK. ACS Synth Biolpubmed:29366323;  doi:10.1021/acssynbio.7b00396

36. Microfluidic platform for selective microparticle parking and paired particle isolation in droplet arrays. Chen L, Kim JJ, Doyle PS. Biomicrofluidicspubmed:29576834;  doi:10.1063/1.5011342

37. Publisher Correction: Temporally precise single-cell-resolution optogenetics. Shemesh OA, Tanese D, Zampini V, Linghu C, Piatkevich K, Ronzitti E, Papagiakoumou E, Boyden ES, Emiliani V. Nat Neuroscipubmed:29549318;  doi:10.1038/s41593-018-0097-1

38. Publisher Correction: A robotic multidimensional directed evolution approach applied to fluorescent voltage reporters. Piatkevich KD, Jung EE, Straub C, Linghu C, Park D, Suk HJ, Hochbaum DR, Goodwin D, Pnevmatikakis E, Pak N, Kawashima T, Yang CT, Rhoades JL, Shemesh O, Asano S, Yoon YG, Freifeld L, Saulnier JL, Riegler C, Engert F, Hughes T, Drobizhev M, Szabo B, Ahrens MB, Flavell SW, Sabatini BL, Boyden ES. Nat Chem Biolpubmed:29520042;  doi:10.1038/s41589-018-0023-6