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: November 2017

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1. Integrated Gut/Liver Microphysiological Systems Elucidates Inflammatory Inter-Tissue Crosstalk. Chen WLK, Edington C, Suter E, Yu J, Velazquez JJ, Velazquez JG, Shockley M, Large EM, Venkataramanan R, Hughes DJ, Stokes CL, Trumper DL, Carrier RL, Cirit M, Griffith LG, Lauffenburger DA. Biotechnol Bioengpubmed:28667746;  doi:10.1002/bit.26370

2. Reexamining opportunities for therapeutic protein production in eukaryotic microorganisms. Bartlett MC, Wright C, Kuo A, Colant N, Westoby M, Love JC. Biotechnol Bioengpubmed:28688187;  doi:10.1002/bit.26378

3. Opportunities and challenges of real-time release testing in biopharmaceutical manufacturing. Jiang M, Severson KA, Love JC, Madden H, Swann P, Zang L, Braatz RD. Biotechnol Bioengpubmed:28710854;  doi:10.1002/bit.26383

4. Catalytic, Conductive Bipolar Membrane Interfaces via Layer-by-Layer Deposition for the Design of Membrane-Integrated Artificial Photosynthesis Systems. McDonald MB, Freund M, Hammond PT. ChemSusChempubmed:29024529;  doi:10.1002/cssc.201701397

5. Engineering and physical sciences in oncology: challenges and opportunities. Mitchell MJ, Jain RK, Langer R. Nat Rev Cancerpubmed:29026204;  doi:10.1038/nrc.2017.83

6. Synthetic RNA-Based Immunomodulatory Gene Circuits for Cancer Immunotherapy. Nissim L, Wu MR, Pery E, Binder-Nissim A, Suzuki HI, Stupp D, Wehrspaun C, Tabach Y, Sharp PA, Lu TK. Cellpubmed:29056342;  doi:10.1016/j.cell.2017.09.049

7. Curative Multicycle Radioimmunotherapy Monitored by Quantitative SPECT/CT-Based Theranostics, Using Bispecific Antibody Pretargeting Strategy in Colorectal Cancer. Cheal SM, Fung EK, Patel M, Xu H, Guo HF, Zanzonico PB, Monette S, Wittrup KD, Cheung NV, Larson SM. J Nucl Medpubmed:28705917;  doi:10.2967/jnumed.117.193250

8. Future cancer research priorities in the USA: a Lancet Oncology Commission. Jaffee EM, Dang CV, Agus DB, Alexander BM, Anderson KC, Ashworth A, Barker AD, Bastani R, Bhatia S, Bluestone JA, Brawley O, Butte AJ, Coit DG, Davidson NE, Davis M, DePinho RA, Diasio RB, Draetta G, Frazier AL, Futreal A, Gambhir SS, Ganz PA, Garraway L, Gerson S, Gupta S, Heath J, Hoffman RI, Hudis C, Hughes-Halbert C, Ibrahim R, Jadvar H, Kavanagh B, Kittles R, Le QT, Lippman SM, Mankoff D, Mardis ER, Mayer DK, McMasters K, Meropol NJ, Mitchell B, Naredi P, Ornish D, Pawlik TM, Peppercorn J, Pomper MG, Raghavan D, Ritchie C, Schwarz SW, Sullivan R, Wahl R, Wolchok JD, Wong SL, Yung A. Lancet Oncolpubmed:29208398;  doi:10.1016/S1470-2045(17)30698-8

9. Near-Infrared Fluorescent Proteins Engineered from Bacterial Phytochromes in Neuroimaging. Piatkevich KD, Suk HJ, Kodandaramaiah SB, Yoshida F, DeGennaro EM, Drobizhev M, Hughes TE, Desimone R, Boyden ES, Verkhusha VV. Biophys Jpubmed:29017728;  doi:10.1016/j.bpj.2017.09.007

10. Submillisecond Optogenetic Control of Neuronal Firing with Two-Photon Holographic Photoactivation of Chronos. Ronzitti E, Conti R, Zampini V, Tanese D, Foust AJ, Klapoetke N, Boyden ES, Papagiakoumou E, Emiliani V. J Neuroscipubmed:28972125;  doi:10.1523/JNEUROSCI.1246-17.2017

11. Cover Image, Volume 114, Number 11, November 2017. Matthews CB, Wright C, Kuo A, Colant N, Westoby M, Love JC. Biotechnol Bioengpubmed:28950044;  doi:10.1002/bit.26169

12. Src Homology 2 domains enhance tyrosine phosphorylation in vivo by protecting binding sites in their target proteins from dephosphorylation. Jadwin JA, Curran TG, Lafontaine AT, White FM, Mayer BJ. J Biol Chempubmed:29162725;  doi:10.1074/jbc.M117.794412

13. T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity. Schmid D, Park CG, Hartl CA, Subedi N, Cartwright AN, Puerto RB, Zheng Y, Maiarana J, Freeman GJ, Wucherpfennig KW, Irvine DJ, Goldberg MS. Nat Communpubmed:29170511;  doi:10.1038/s41467-017-01830-8

14. Radiation-enhanced delivery of systemically administered amphiphilic-CpG oligodeoxynucleotide. Appelbe OK, Moynihan KD, Flor A, Rymut N, Irvine DJ, Kron SJ. J Control Releasepubmed:28987882;  doi:10.1016/j.jconrel.2017.09.043

15. CD38 bispecific antibody pretargeted radioimmunotherapy for multiple myeloma and other B cell malignancies. Green DJ, O'Steen S, Lin Y, Comstock ML, Kenoyer AL, Hamlin DK, Wilbur DS, Fisher DR, Nartea M, Hylarides MD, Gopal AK, Gooley TA, Orozco JJ, Till BG, Orcutt KD, Wittrup KD, Press OW. Bloodpubmed:29158362;  doi:10.1182/blood-2017-09-807610

16. Characterization of in vivo resistance to osimertinib and JNJ-61186372, an EGFR/Met bi-specific antibody, reveals unique and consensus mechanisms of resistance. Emdal KB, Dittmann A, Reddy RJ, Lescarbeau RS, Moores SL, Laquerre S, White FM. Mol Cancer Therpubmed:28830985;  doi:10.1158/1535-7163.MCT-17-0413

17. A robust cell culture system supporting the complete life cycle of hepatitis B virus. Michailidis E, Pabon J, Xiang K, Park P, Ramanan V, Hoffmann HH, Schneider WM, Bhatia SN, de Jong YP, Shlomai A, Rice CM. Sci Reppubmed:29192196;  doi:10.1038/s41598-017-16882-5

18. Targeting STUB1-tissue factor axis normalizes hyperthrombotic uremic phenotype without increasing bleeding risk. Shashar M, Belghasem ME, Matsuura S, Walker J, Richards S, Alousi F, Rijal K, Kolachalama VB, Balcells M, Odagi M, Nagasawa K, Henderson JM, Gautam A, Rushmore R, Francis J, Kirchhofer D, Kolandaivelu K, Sherr DH, Edelman ER, Ravid K, Chitalia VC. Sci Transl Medpubmed:29167396;  doi:10.1126/scitranslmed.aam8475

19. Needles in Our Technology Haystacks: Defining Efficacy Is Easy, Characterizing Complications Is the Challenge. Edelman ER, Wang PJ. Circ Cardiovasc Intervpubmed:29146674;  doi:10.1161/CIRCINTERVENTIONS.117.006059

20. Vessel centerline reconstruction from non-isocentric and non-orthogonal paired monoplane angiographic images. Kunio M, O'Brien CC, Lopes ACJr, Bailey L, Lemos PA, Tearney GJ, Edelman ER. Int J Cardiovasc Imagingpubmed:29139034;  doi:10.1007/s10554-017-1275-z

21. 3D matrix embedding inhibits cycloheximide-mediated sensitization to TNF-alpha-induced apoptosis of human endothelial cells. Saemisch M, Nickmann M, Riesinger L, Edelman ER, Methe H. J Tissue Eng Regen Medpubmed:29131527;  doi:10.1002/term.2609

22. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Adalsteinsson VA, Ha G, Freeman SS, Choudhury AD, Stover DG, Parsons HA, Gydush G, Reed SC, Rotem D, Rhoades J, Loginov D, Livitz D, Rosebrock D, Leshchiner I, Kim J, Stewart C, Rosenberg M, Francis JM, Zhang CZ, Cohen O, Oh C, Ding H, Polak P, Lloyd M, Mahmud S, Helvie K, Merrill MS, Santiago RA, O'Connor EP, Jeong SH, Leeson R, Barry RM, Kramkowski JF, Zhang Z, Polacek L, Lohr JG, Schleicher M, Lipscomb E, Saltzman A, Oliver NM, Marini L, Waks AG, Harshman LC, Tolaney SM, Van Allen EM, Winer EP, Lin NU, Nakabayashi M, Taplin ME, Johannessen CM, Garraway LA, Golub TR, Boehm JS, Wagle N, Getz G, Love JC, Meyerson M. Nat Communpubmed:29109393;  doi:10.1038/s41467-017-00965-y

23. Microfluidic platform for characterizing TCR-pMHC interactions. Stockslager MA, Bagnall JS, Hecht VC, Hu K, Aranda-Michel E, Payer K, Kimmerling RJ, Manalis SR. Biomicrofluidicspubmed:29204244;  doi:10.1063/1.5002116

24. Determining therapeutic susceptibility in multiple myeloma by single-cell mass accumulation. Cetin AE, Stevens MM, Calistri NL, Fulciniti M, Olcum S, Kimmerling RJ, Munshi NC, Manalis SR. Nat Communpubmed:29151572;  doi:10.1038/s41467-017-01593-2

25. Emerging mechanisms of long noncoding RNA function during normal and malignant hematopoiesis. Alvarez-Dominguez JR, Lodish HF. Bloodpubmed:28928124;  doi:10.1182/blood-2017-06-788695

26. The BRAIN Initiative Cell Census Consortium: Lessons Learned toward Generating a Comprehensive Brain Cell Atlas. Ecker JR, Geschwind DH, Kriegstein AR, Ngai J, Osten P, Polioudakis D, Regev A, Sestan N, Wickersham IR, Zeng H. Neuronpubmed:29096072;  doi:10.1016/j.neuron.2017.10.007

27. Efficient Generation of Transcriptomic Profiles by Random Composite Measurements. Cleary B, Cong L, Cheung A, Lander ES, Regev A. Cellpubmed:29153835;  doi:10.1016/j.cell.2017.10.023

28. S-Nitrosylation of PINK1 Attenuates PINK1/Parkin-Dependent Mitophagy in hiPSC-Based Parkinson's Disease Models. Oh CK, Sultan A, Platzer J, Dolatabadi N, Soldner F, McClatchy DB, Diedrich JK, Yates JR3rd, Ambasudhan R, Nakamura T, Jaenisch R, Lipton SA. Cell Reppubmed:29166608;  doi:10.1016/j.celrep.2017.10.068

29. A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Hall AB, Yassour M, Sauk J, Garner A, Jiang X, Arthur T, Lagoudas GK, Vatanen T, Fornelos N, Wilson R, Bertha M, Cohen M, Garber J, Khalili H, Gevers D, Ananthakrishnan AN, Kugathasan S, Lander ES, Blainey P, Vlamakis H, Xavier RJ, Huttenhower C. Genome Medpubmed:29183332;  doi:10.1186/s13073-017-0490-5

30. Periodic production of retinoic acid by meiotic and somatic cells coordinates four transitions in mouse spermatogenesis. Endo T, Freinkman E, de Rooij DG, Page DC. Proc Natl Acad Sci U S Apubmed:29109271;  doi:10.1073/pnas.1710837114

31. TOX Regulates Growth, DNA Repair, and Genomic Instability in T-cell Acute Lymphoblastic Leukemia. Lobbardi R, Pinder J, Martinez-Pastor B, Theodorou M, Blackburn JS, Abraham BJ, Namiki Y, Mansour M, Abdelfattah NS, Molodtsov A, Alexe G, Toiber D, de Waard M, Jain E, Boukhali M, Lion M, Bhere D, Shah K, Gutierrez A, Stegmaier K, Silverman LB, Sadreyev RI, Asara JM, Oettinger MA, Haas W, Look AT, Young RA, Mostoslavsky R, Dellaire G, Langenau DM. Cancer Discovpubmed:28974511;  doi:10.1158/2159-8290.CD-17-0267

32. Fifty years of mentoring and advising. Lodish HF. Mol Biol Cellpubmed:29084906;  doi:10.1091/mbc.E17-07-0481

33. Detection of long repeat expansions from PCR-free whole-genome sequence data. Dolzhenko E, van Vugt JJFA, Shaw RJ, Bekritsky MA, van Blitterswijk M, Narzisi G, Ajay SS, Rajan V, Lajoie B, Johnson NH, Kingsbury Z, Humphray SJ, Schellevis RD, Brands WJ, Baker M, Rademakers R, Kooyman M, Tazelaar GHP, van Es MA, McLaughlin R, Sproviero W, Shatunov A, Jones A, Al Khleifat A, Pittman A, Morgan S, Hardiman O, Al-Chalabi A, Shaw C, Smith B, Neo EJ, Morrison K, Shaw P, Reeves C, Winterkorn L, Wexler NS, Housman DE, Ng CW, Li AL, Taft RJ, van den Berg LH, Bentley DR, Veldink JH, Eberle MA. Genome Respubmed:28887402;  doi:10.1101/gr.225672.117

34. A single-cell survey of the small intestinal epithelium. Haber AL, Biton M, Rogel N, Herbst RH, Shekhar K, Smillie C, Burgin G, Delorey TM, Howitt MR, Katz Y, Tirosh I, Beyaz S, Dionne D, Zhang M, Raychowdhury R, Garrett WS, Rozenblatt-Rosen O, Shi HN, Yilmaz O, Xavier RJ, Regev A. Naturepubmed:29144463;  doi:10.1038/nature24489

35. Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer. Ebot EM, Gerke T, Labbe DP, Sinnott JA, Zadra G, Rider JR, Tyekucheva S, Wilson KM, Kelly RS, Shui IM, Loda M, Kantoff PW, Finn S, Vander Heiden MG, Brown M, Giovannucci EL, Mucci LA. Cancerpubmed:28700821;  doi:10.1002/cncr.30831

36. Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis. Romero R, Sayin VI, Davidson SM, Bauer MR, Singh SX, LeBoeuf SE, Karakousi TR, Ellis DC, Bhutkar A, Sanchez-Rivera FJ, Subbaraj L, Martinez B, Bronson RT, Prigge JR, Schmidt EE, Thomas CJ, Goparaju C, Davies A, Dolgalev I, Heguy A, Allaj V, Poirier JT, Moreira AL, Rudin CM, Pass HI, Vander Heiden MG, Jacks T, Papagiannakopoulos T. Nat Medpubmed:28967920;  doi:10.1038/nm.4407

37. A Genetic Tool to Track Protein Aggregates and Control Prion Inheritance. Newby GA, Kiriakov S, Hallacli E, Kayatekin C, Tsvetkov P, Mancuso CP, Bonner JM, Hesse WR, Chakrabortee S, Manogaran AL, Liebman SW, Lindquist S, Khalil AS. Cellpubmed:29056345;  doi:10.1016/j.cell.2017.09.041

38. Intersubunit Crosstalk in the Rag GTPase Heterodimer Enables mTORC1 to Respond Rapidly to Amino Acid Availability. Shen K, Choe A, Sabatini DM. Mol Cellpubmed:29056322;  doi:10.1016/j.molcel.2017.09.026

39. Pioneer cells established by the [SWI+] prion can promote dispersal and out-crossing in yeast. Newby GA, Lindquist S. PLoS Biolpubmed:29135981;  doi:10.1371/journal.pbio.2003476

40. Height, obesity, and the risk of TMPRSS2:ERG-defined prostate cancer. Graff RE, Ahearn TU, Pettersson A, Ebot EM, Gerke T, Penney KL, Wilson KM, Markt SC, Pernar CH, Gonzalez-Feliciano AG, Song M, Lis RT, Schmidt DR, Vander Heiden MG, Fiorentino M, Giovannucci EL, Loda M, Mucci LA. Cancer Epidemiol Biomarkers Prevpubmed:29167279;  doi:10.1158/1055-9965.EPI-17-0547

41. SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway. Gu X, Orozco JM, Saxton RA, Condon KJ, Liu GY, Krawczyk PA, Scaria SM, Harper JW, Gygi SP, Sabatini DM. Sciencepubmed:29123071;  doi:10.1126/science.aao3265

42. NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Alvarez SW, Sviderskiy VO, Terzi EM, Papagiannakopoulos T, Moreira AL, Adams S, Sabatini DM, Birsoy K, Possemato R. Naturepubmed:29168506;  doi:10.1038/nature24637

43. Lysosomal metabolomics reveals V-ATPase and mTOR-dependent regulation of amino acid efflux from lysosomes. Abu-Remaileh M, Wyant GA, Kim C, Laqtom NN, Abbasi M, Chan SH, Freinkman E, Sabatini DM. Sciencepubmed:29074583;  doi:10.1126/science.aan6298

44. Twenty-five years of mTOR: Uncovering the link from nutrients to growth. Sabatini DM. Proc Natl Acad Sci U S Apubmed:29078414;  doi:10.1073/pnas.1716173114

45. 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

46. The SUMO guards for SNAIL. Ye X, Weinberg RA. Oncotargetpubmed:29231927;  doi:10.18632/oncotarget.22432

47. Perfluoroarene-Based Peptide Macrocycles to Enhance Penetration Across the Blood-Brain Barrier. Fadzen C, Wolfe J, Cho CF, Chiocca EA, Lawler S, Pentelute BL. J Am Chem Socpubmed:28992407;  doi:10.1021/jacs.7b09790

48. Library design-facilitated high-throughput sequencing of synthetic peptide libraries. Vinogradov AA, Gates ZP, Zhang C, Quartararo AJ, Halloran KH, Pentelute BL. ACS Comb Scipubmed:28892357;  doi:10.1021/acscombsci.7b00109