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 2017

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1. Advancing therapeutic applications of synthetic gene circuits. Higashikuni Y, Chen WC, Lu TK. Curr Opin Biotechnolpubmed:28750201;  doi:10.1016/j.copbio.2017.06.011

2. Menopausal hormone therapy for primary prevention: why the USPSTF is wrong. Langer RD, Simon JA, Pines A, Lobo RA, Hodis HN, Pickar JH, Archer DF, Sarrel PM, Utian WH. Menopausepubmed:28872490;  doi:10.1097/GME.0000000000000983

3. DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Tregs. Janssen E, Kumari S, Tohme M, Ullas S, Barrera V, Tas JM, Castillo-Rama M, Bronson RT, Usmani SM, Irvine DJ, Mempel TR, Geha RS. JCI Insightpubmed:28978806;  doi:10.1172/jci.insight.94298

4. Nonspecificity in a nonimmune human scFv repertoire. Kelly RL, Zhao J, Le D, Wittrup KD. MAbspubmed:28910564;  doi:10.1080/19420862.2017.1356528

5. Chaperone proteins as single component reagents to assess antibody nonspecificity. Kelly RL, Geoghegan JC, Feldman J, Jain T, Kauke M, Le D, Zhao J, Wittrup KD. MAbspubmed:28745541;  doi:10.1080/19420862.2017.1356529

6. Tumor-Penetrating Delivery of siRNA against TNFalpha to Human Vestibular Schwannomas. Ren Y, Sagers JE, Landegger LD, Bhatia SN, Stankovic KM. Sci Reppubmed:29018206;  doi:10.1038/s41598-017-13032-9

7. Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis. Tzafriri AR, Garcia-Polite F, Zani B, Stanley J, Muraj B, Knutson J, Kohler R, Markham P, Nikanorov A, Edelman ER. J Control Releasepubmed:28867375;  doi:10.1016/j.jconrel.2017.08.037

8. Polyamine-Mediated Stoichiometric Assembly of Ribonucleoproteins for Enhanced mRNA Delivery. Li J, He Y, Wang W, Wu C, Hong C, Hammond PT. Angew Chem Int Ed Englpubmed:28925033;  doi:10.1002/anie.201707466

9. Erratum: Characterization of Mechanically Matched Hydrogel Coatings to Improve the Biocompatibility of Neural Implants. Spencer KC, Sy JC, Ramadi KB, Graybiel AM, Langer R, Cima MJ. Sci Reppubmed:28993678;  doi:10.1038/s41598-017-12312-8

10. Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics. Bertrand N, Grenier P, Mahmoudi M, Lima EM, Appel EA, Dormont F, Lim JM, Karnik R, Langer R, Farokhzad OC. Nat Communpubmed:28974673;  doi:10.1038/s41467-017-00600-w

11. Oral delivery of biologics using drug-device combinations. Caffarel-Salvador E, Abramson A, Langer R, Traverso G. Curr Opin Pharmacolpubmed:28779684;  doi:10.1016/j.coph.2017.07.003

12. Antimicrobial Peptides: Role in Human Disease and Potential as Immunotherapies. de la Fuente-Nunez C, Silva ON, Lu TK, Franco OL. Pharmacol Therpubmed:28435091;  doi:10.1016/j.pharmthera.2017.04.002

13. An Engineered Synthetic Pathway for Discovering Nonnatural Nonribosomal Peptides in Escherichia coli. Cleto S, Lu TK. MBiopubmed:29018120;  doi:10.1128/mBio.01474-17

14. Biocompatibility, bone healing, and safety evaluation in rabbits with an IlluminOss bone stabilization system. McSweeney AL, Zani BG, Baird R, Stanley JR, Hayward A, Markham PM, Kopia GA, Edelman ER, Rabiner R. J Orthop Respubmed:28135014;  doi:10.1002/jor.23532

15. Randomized Comparison of Ridaforolimus-Eluting and Zotarolimus-Eluting Coronary Stents in Patients with Coronary Artery Disease: Primary Results from the BIONICS Trial. Kandzari DE, Smits PC, Love MP, Ben-Yehuda O, Banai S, Robinson SD, Jonas M, Kornowski R, Bagur R, Iniguez A, Danenberg HD, Feldman RL, Jauhar R, Chandna H, Parikh MA, Perlman GY, Balcells M, Markham PM, Ozan MO, Genereux P, Edelman E, Leon MB, Stone GW. Circulationpubmed:28794001;  doi:10.1161/CIRCULATIONAHA.117.028885

16. Roles for Innate Immunity in Combination Immunotherapies. Moynihan KD, Irvine DJ. Cancer Respubmed:28928130;  doi:10.1158/0008-5472.CAN-17-1340

17. Randomized CRISPR-Cas Transcriptional Perturbation Screening Reveals Protective Genes against Alpha-Synuclein Toxicity. Chen YC, Farzadfard F, Gharaei N, Chen WCW, Cao J, Lu TK. Mol Cellpubmed:28985507;  doi:10.1016/j.molcel.2017.09.014

18. The Human Cell Atlas: from vision to reality. Rozenblatt-Rosen O, Stubbington MJT, Regev A, Teichmann SA. Naturepubmed:29072289;  doi:10.1038/550451a

19. Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells. Semrau S, Goldmann JE, Soumillon M, Mikkelsen TS, Jaenisch R, van Oudenaarden A. Nat Communpubmed:29061959;  doi:10.1038/s41467-017-01076-4

20. Human Embryo Editing: Opportunities and Importance of Transnational Cooperation. Pei D, Beier DW, Levy-Lahad E, Marchant G, Rossant J, Izpisua Belmonte JC, Lovell-Badge R, Jaenisch R, Charo A, Baltimore D. Cell Stem Cellpubmed:28985523;  doi:10.1016/j.stem.2017.09.010

21. An Endogenously Tagged Fluorescent Fusion Protein Library in Mouse Embryonic Stem Cells. Harikumar A, Edupuganti RR, Sorek M, Azad GK, Markoulaki S, Sehnalova P, Legartova S, Bartova E, Farkash-Amar S, Jaenisch R, Alon U, Meshorer E. Stem Cell Reportspubmed:28966122;  doi:10.1016/j.stemcr.2017.08.022

22. Alternative SET/TAFI Promoters Regulate Embryonic Stem Cell Differentiation. Edupuganti RR, Harikumar A, Aaronson Y, Biran A, Sailaja BS, Nissim-Rafinia M, Azad GK, Cohen MA, Park JE, Shivalila CS, Markoulaki S, Sze SK, Jaenisch R, Meshorer E. Stem Cell Reportspubmed:28966118;  doi:10.1016/j.stemcr.2017.08.021

23. Activation of the p53 Transcriptional Program Sensitizes Cancer Cells to Cdk7 Inhibitors. Kalan S, Amat R, Schachter MM, Kwiatkowski N, Abraham BJ, Liang Y, Zhang T, Olson CM, Larochelle S, Young RA, Gray NS, Fisher RP. Cell Reppubmed:29020632;  doi:10.1016/j.celrep.2017.09.056

24. HSF1-dependent and -independent regulation of the mammalian in vivo heat shock response and its impairment in Huntington's disease mouse models. Neueder A, Gipson TA, Batterton S, Lazell HJ, Farshim PP, Paganetti P, Housman DE, Bates GP. Sci Reppubmed:28970536;  doi:10.1038/s41598-017-12897-0

25. Landscape of X chromosome inactivation across human tissues. Tukiainen T, Villani AC, Yen A, Rivas MA, Marshall JL, Satija R, Aguirre M, Gauthier L, Fleharty M, Kirby A, Cummings BB, Castel SE, Karczewski KJ, Aguet F, Byrnes A, Lappalainen T, Regev A, Ardlie KG, Hacohen N, MacArthur DG. Naturepubmed:29022598;  doi:10.1038/nature24265

26. Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution. Mathys H, Adaikkan C, Gao F, Young JZ, Manet E, Hemberg M, De Jager PL, Ransohoff RM, Regev A, Tsai LH. Cell Reppubmed:29020624;  doi:10.1016/j.celrep.2017.09.039

27. Single-cell transcriptomics to explore the immune system in health and disease. Stubbington MJT, Rozenblatt-Rosen O, Regev A, Teichmann SA. Sciencepubmed:28983043;  doi:10.1126/science.aan6828

28. RNA targeting with CRISPR-Cas13. Abudayyeh OO, Gootenberg JS, Essletzbichler P, Han S, Joung J, Belanto JJ, Verdine V, Cox DBT, Kellner MJ, Regev A, Lander ES, Voytas DF, Ting AY, Zhang F. Naturepubmed:28976959;  doi:10.1038/nature24049

29. AAV-mediated direct in vivo CRISPR screen identifies functional suppressors in glioblastoma. Chow RD, Guzman CD, Wang G, Schmidt F, Youngblood MW, Ye L, Errami Y, Dong MB, Martinez MA, Zhang S, Renauer P, Bilguvar K, Gunel M, Sharp PA, Zhang F, Platt RJ, Chen S. Nat Neuroscipubmed:28805815;  doi:10.1038/nn.4620

30. A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer. Polak P, Kim J, Braunstein LZ, Karlic R, Haradhavala NJ, Tiao G, Rosebrock D, Livitz D, Kubler K, Mouw KW, Kamburov A, Maruvka YE, Leshchiner I, Lander ES, Golub TR, Zick A, Orthwein A, Lawrence MS, Batra RN, Caldas C, Haber DA, Laird PW, Shen H, Ellisen LW, D'Andrea AD, Chanock SJ, Foulkes WD, Getz G. Nat Genetpubmed:28825726;  doi:10.1038/ng.3934

31. Massively parallel single-nucleus RNA-seq with DroNc-seq. Habib N, Avraham-Davidi I, Basu A, Burks T, Shekhar K, Hofree M, Choudhury SR, Aguet F, Gelfand E, Ardlie K, Weitz DA, Rozenblatt-Rosen O, Zhang F, Regev A. Nat Methodspubmed:28846088;  doi:10.1038/nmeth.4407

32. Coordinated Splicing of Regulatory Detained Introns within Oncogenic Transcripts Creates an Exploitable Vulnerability in Malignant Glioma. Braun CJ, Stanciu M, Boutz PL, Patterson JC, Calligaris D, Higuchi F, Neupane R, Fenoglio S, Cahill DP, Wakimoto H, Agar NYR, Yaffe MB, Sharp PA, Hemann MT, Lees JA. Cancer Cellpubmed:28966034;  doi:10.1016/j.ccell.2017.08.018

33. Cohesin Loss Eliminates All Loop Domains. Rao SSP, Huang SC, Glenn St Hilaire B, Engreitz JM, Perez EM, Kieffer-Kwon KR, Sanborn AL, Johnstone SE, Bascom GD, Bochkov ID, Huang X, Shamim MS, Shin J, Turner D, Ye Z, Omer AD, Robinson JT, Schlick T, Bernstein BE, Casellas R, Lander ES, Aiden EL. Cellpubmed:28985562;  doi:10.1016/j.cell.2017.09.026

34. Survival of pancreatic cancer cells lacking KRAS function. Muzumdar MD, Chen PY, Dorans KJ, Chung KM, Bhutkar A, Hong E, Noll EM, Sprick MR, Trumpp A, Jacks T. Nat Communpubmed:29061961;  doi:10.1038/s41467-017-00942-5

35. Activation of the NRF2 antioxidant program generates an imbalance in central carbon metabolism in cancer. Sayin VI, LeBoeuf SE, Singh SX, Davidson SM, Biancur D, Guzelhan BS, Alvarez SW, Wu WL, Karakousi TR, Zavitsanou AM, Ubriaco J, Muir A, Karagiannis D, Morris PJ, Thomas CJ, Possemato R, Vander Heiden MG, Papagiannakopoulos T. Elifepubmed:28967864;  doi:10.7554/eLife.28083

36. Aneuploid cell survival relies upon sphingolipid homeostasis. Tang YC, Yuwen H, Wang K, Bruno PM, Bullock K, Deik AA, Santaguida S, Trakala M, Pfau SJ, Zhong N, Huang T, Wang L, Clish CB, Hemann MT, Amon A. Cancer Respubmed:28775166;  doi:10.1158/0008-5472.CAN-17-0049

37. mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient. Wyant GA, Abu-Remaileh M, Wolfson RL, Chen WW, Freinkman E, Danai LV, Vander Heiden MG, Sabatini DM. Cellpubmed:29053970;  doi:10.1016/j.cell.2017.09.046

38. EMT, CSCs, and drug resistance: the mechanistic link and clinical implications. Shibue T, Weinberg RA. Nat Rev Clin Oncolpubmed:28397828;  doi:10.1038/nrclinonc.2017.44

39. Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1. Feng YX, Jin DX, Sokol ES, Reinhardt F, Miller DH, Gupta PB. Nat Communpubmed:29057869;  doi:10.1038/s41467-017-01052-y

40. Heterochiral Knottin Protein: Folding and Solution Structure. Mong S, Cochran F, Yu H, Graziano ZA, Lin YS, Cochran JR, Pentelute BL. Biochemistrypubmed:28952732;  doi:10.1021/acs.biochem.7b00722