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: December 2016

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1. Nanoscience and Nanotechnology Impacting Diverse Fields of Science, Engineering, and Medicine. Chan WW, Chhowalla M, Glotzer S, Gogotsi Y, Hafner JH, Hammond PT, Hersam MC, Javey A, Kagan CR, Khademhosseini A, Kotov NA, Lee ST, Li Y, Mohwald H, Mulvaney PA, Nel AE, Nordlander PJ, Parak WJ, Penner RM, Rogach AL, Schaak RE, Stevens MM, Wee AT, Willson CG, Fernandez LE, Weiss PS. ACS Nano. pubmed:28024354;  doi:10.1021/acsnano.6b08335

2. Special issue: Polylactide (PLA) Based Biopolymers. Langer R, Basu A, Domb AJ. Adv Drug Deliv Rev. pubmed:27938692;  doi:10.1016/j.addr.2016.11.002

3. Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy. Griffiths KL, Ahmed M, Das S, Gopal R, Horne W, Connell TD, Moynihan KD, Kolls JK, Irvine DJ, Artyomov MN, Rangel-Moreno J, Khader SA. Nat Commun. pubmed:28004802;  doi:10.1038/ncomms13894

4. Temporally Programmed CD8alpha+ DC Activation Enhances Combination Cancer Immunotherapy. Tzeng A, Kauke MJ, Zhu EF, Moynihan KD, Opel CF, Yang NJ, Mehta N, Kelly RL, Szeto GL, Overwijk WW, Irvine DJ, Wittrup KD. Cell Rep. pubmed:27926855;  doi:10.1016/j.celrep.2016.11.020

5. A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties. Clark AM, Wheeler SE, Young CL, Stockdale L, Shepard Neiman J, Zhao W, Stolz DB, Venkataramanan R, Lauffenburger D, Griffith L, Wells A. Lab Chip. pubmed:27910972;  doi:10.1039/c6lc01171c

6. Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses. Moynihan KD, Opel CF, Szeto GL, Tzeng A, Zhu EF, Engreitz JM, Williams RT, Rakhra K, Zhang MH, Rothschilds AM, Kumari S, Kelly RL, Kwan BH, Abraham W, Hu K, Mehta NK, Kauke MJ, Suh H, Cochran JR, Lauffenburger DA, Wittrup KD, Irvine DJ. Nat Med. pubmed:27775706;  doi:10.1038/nm.4200

7. Genome-wide CRISPR Screen Identifies Regulators of MAPK as Suppressors of Liver Tumors in Mice. Song CQ, Li Y, Mou H, Moore J, Park A, Pomyen Y, Hough S, Kennedy Z, Fischer A, Yin H, Anderson DG, Conte DJr, Zender L, Wang XW, Thorgeirsson S, Weng Z, Xue W. Gastroenterology. pubmed:27956228;  doi:10.1053/j.gastro.2016.12.002

8. Efficacy and immunogenicity of unmodified and pseudouridine-modified mRNA delivered systemically with lipid nanoparticles in vivo. Kauffman KJ, Mir FF, Jhunjhunwala S, Kaczmarek JC, Hurtado JE, Yang JH, Webber MJ, Kowalski PS, Heartlein MW, DeRosa F, Anderson DG. Biomaterials. pubmed:27680591;  doi:10.1016/j.biomaterials.2016.09.006

9. Ultra-Hydrophilic Stent Platforms Promote Early Vascular Healing and Minimize Late Tissue Response - A Potential Alternative to Second-Generation Drug Eluting Stents. Kolandaivelu K, Bailey L, Buzzi S, Zucker A, Milleret V, Ziogas A, Ehrbar M, Khattab AA, Stanley JR, Wong GK, Zani B, Markham PM, Tzafriri AR, Bhatt DL, Edelman ER. EuroIntervention. pubmed:27993749;  doi:10.4244/EIJ-D-15-00497

10. Modeling therapeutic antibody-small molecule drug-drug interactions using a 3D perfusable human liver co-culture platform. Long TJ, Cosgrove PA, Dunn RT, Stolz DB, Hamadeh HK, Afshari C, McBride H, Griffith LG. Drug Metab Dispos. pubmed:27621203;  doi:10.1124/dmd.116.071456

11. Direct evidence for cancer-cell-autonomous extracellular protein catabolism in pancreatic tumors. Davidson SM, Jonas O, Keibler MA, Hou HW, Luengo A, Mayers JR, Wyckoff J, Del Rosario AM, Whitman M, Chin CR, Condon KJ, Lammers A, Kellersberger KA, Stall BK, Stephanopoulos G, Bar-Sagi D, Han J, Rabinowitz JD, Cima MJ, Langer R, Vander Heiden MG. Nat Med. pubmed:28024083;  doi:10.1038/nm.4256

12. A Facile and Versatile Method to Endow Biomaterial Devices with Zwitterionic Surface Coatings. Yesilyurt V, Veiseh O, Doloff JC, Li J, Bose S, Xie X, Bader AR, Chen M, Webber MJ, Vegas AJ, Langer R, Anderson DG. Adv Healthc Mater. pubmed:27976536;  doi:10.1002/adhm.201601091

13. Scalable manufacturing of biomimetic moldable hydrogels for industrial applications. Yu AC, Chen H, Chan D, Agmon G, Stapleton LM, Sevit AM, Tibbitt MW, Acosta JD, Zhang T, Franzia PW, Langer R, Appel EA. Proc Natl Acad Sci U S A. pubmed:27911849;  doi:10.1073/pnas.1618156113

14. Supramolecular PEGylation of biopharmaceuticals. Webber MJ, Appel EA, Vinciguerra B, Cortinas AB, Thapa LS, Jhunjhunwala S, Isaacs L, Langer R, Anderson DG. Proc Natl Acad Sci U S A. pubmed:27911829;  doi:10.1073/pnas.1616639113

15. Progress in Formulation-Based Approaches for Antiretrovirals. Kirtane AR, Langer R, Traverso G. J Pharm Sci. pubmed:27771050;  doi:10.1016/j.xphs.2016.09.015

16. Physical and mechanical properties of PLA, and their functions in widespread applications - A comprehensive review. Farah S, Anderson DG, Langer R. Adv Drug Deliv Rev. pubmed:27356150;  doi:10.1016/j.addr.2016.06.012

17. Parallel in-vivo assessment of drug phenotypes at various time points during systemic BRAF inhibition reveals tumor adaptation and altered treatment vulnerabilities. Jonas O, Oudin MJ, Kosciuk T, Whitman M, Gertler FB, Cima MJ, Flaherty KT, Langer R. Clin Cancer Res. pubmed:27091406;  doi:10.1158/1078-0432.CCR-15-2722

18. Diversity of Antiviral IgG Effector Activities Observed in HIV-Infected and Vaccinated Subjects. Huang Y, Ferrari G, Alter G, Forthal DN, Kappes JC, Lewis GK, Love JC, Borate B, Harris L, Greene K, Gao H, Phan TB, Landucci G, Goods BA, Dowell KG, Cheng HD, Bailey-Kellogg C, Montefiori DC, Ackerman ME. J Immunol. pubmed:27913647;  doi:10.4049/jimmunol.1601197

19. Direct single-cell biomass estimates for marine bacteria via Archimedes' principle. Cermak N, Becker JW, Knudsen SM, Chisholm SW, Manalis SR, Polz MF. ISME J. pubmed:27922599;  doi:10.1038/ismej.2016.161

20. Nuclear Magnetic Resonance and Molecular Dynamics Simulation of the Interaction between Recognition Protein H7 of the Novel Influenza Virus H7N9 and Glycan Cell Surface Receptors. Macchi E, Rudd TR, Raman R, Sasisekharan R, Yates EA, Naggi A, Guerrini M, Elli S. Biochemistry. pubmed:27933797;  doi:10.1021/acs.biochem.6b00693

21. A Structural and Mathematical Modeling Analysis of the Likelihood of Antibody-Dependent Enhancement in Influenza. Ramakrishnan B, Viswanathan K, Tharakaraman K, Dancik V, Raman R, Babcock GJ, Shriver Z, Sasisekharan R. Trends Microbiol. pubmed:27751627;  doi:10.1016/j.tim.2016.09.003

22. Human Naive Pluripotent Stem Cells Model X Chromosome Dampening and X Inactivation. Sahakyan A, Kim R, Chronis C, Sabri S, Bonora G, Theunissen TW, Kuoy E, Langerman J, Clark AT, Jaenisch R, Plath K. Cell Stem Cell. pubmed:27989770;  doi:10.1016/j.stem.2016.10.006

23. Stem cells and interspecies chimaeras. Wu J, Greely HT, Jaenisch R, Nakauchi H, Rossant J, Belmonte JC. Nature. pubmed:27905428;  doi:10.1038/nature20573

24. CNS disease models with human pluripotent stem cells in the CRISPR age. Muffat J, Li Y, Jaenisch R. Curr Opin Cell Biol. pubmed:27768957;  doi:10.1016/j.ceb.2016.10.001

25. Comprehensive population-based genome sequencing provides insight into hematopoietic regulatory mechanisms. Guo MH, Nandakumar SK, Ulirsch JC, Zekavat SM, Buenrostro JD, Natarajan P, Salem RM, Chiarle R, Mitt M, Kals M, Parn K, Fischer K, Milani L, Magi R, Palta P, Gabriel SB, Metspalu A, Lander ES, Kathiresan S, Hirschhorn JN, Esko T, Sankaran VG. Proc Natl Acad Sci U S A. pubmed:28031487;  doi:10.1073/pnas.1619052114

26. Phenotypic Characterization of Genetically Lowered Human Lipoprotein(a) Levels. Emdin CA, Khera AV, Natarajan P, Klarin D, Won HH, Peloso GM, Stitziel NO, Nomura A, Zekavat SM, Bick AG, Gupta N, Asselta R, Duga S, Merlini PA, Correa A, Kessler T, Wilson JG, Bown MJ, Hall AS, Braund PS, Samani NJ, Schunkert H, Marrugat J, Elosua R, McPherson R, Farrall M, Watkins H, Willer C, Abecasis GR, Felix JF, Vasan RS, Lander E, Rader DJ, Danesh J, Ardissino D, Gabriel S, Saleheen D, Kathiresan S. J Am Coll Cardiol. pubmed:28007139;  doi:10.1016/j.jacc.2016.10.033

27. Generation of Immunity against Pathogens via Single-Domain Antibody-Antigen Constructs. Duarte JN, Cragnolini JJ, Swee LK, Bilate AM, Bader J, Ingram JR, Rashidfarrokhi A, Fang T, Schiepers A, Hanke L, Ploegh HL. J Immunol. pubmed:27821668;  doi:10.4049/jimmunol.1600692

28. Unrestrained AMPylation targets cytosolic chaperones and activates the heat shock response. Truttmann MC, Zheng X, Hanke L, Damon JR, Grootveld M, Krakowiak J, Pincus D, Ploegh HL. Proc Natl Acad Sci U S A. pubmed:28031489;  doi:10.1073/pnas.1619234114

29. The Antiviral Mechanism of an Influenza A Virus Nucleoprotein-Specific Single-Domain Antibody Fragment. Hanke L, Knockenhauer KE, Brewer RC, van Diest E, Schmidt FI, Schwartz TU, Ploegh HL. MBio. pubmed:27965447;  doi:10.1128/mBio.01569-16

30. Crystal Structure and Conformational Change Mechanism of a Bacterial Nramp-Family Divalent Metal Transporter. Bozzi AT, Bane LB, Weihofen WA, Singharoy A, Guillen ER, Ploegh HL, Schulten K, Gaudet R. Structure. pubmed:27839948;  doi:10.1016/j.str.2016.09.017

31. TGF-beta inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors. Gao X, Lee HY, da Rocha EL, Zhang C, Lu YF, Li D, Feng Y, Ezike J, Elmes RR, Barrasa MI, Cahan P, Li H, Daley GQ, Lodish HF. Blood. pubmed:27777239;  doi:10.1182/blood-2016-05-718320

32. A genome-wide CRISPR screen identifies a restricted set of HIV host dependency factors. Park RJ, Wang T, Koundakjian D, Hultquist JF, Lamothe-Molina P, Monel B, Schumann K, Yu H, Krupzcak KM, Garcia-Beltran W, Piechocka-Trocha A, Krogan NJ, Marson A, Sabatini DM, Lander ES, Hacohen N, Walker BD. Nat Genet. pubmed:27992415;  doi:10.1038/ng.3741

33. A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response. Adamson B, Norman TM, Jost M, Cho MY, Nunez JK, Chen Y, Villalta JE, Gilbert LA, Horlbeck MA, Hein MY, Pak RA, Gray AN, Gross CA, Dixit A, Parnas O, Regev A, Weissman JS. Cell. pubmed:27984733;  doi:10.1016/j.cell.2016.11.048

34. Perturb-Seq: Dissecting Molecular Circuits with Scalable Single-Cell RNA Profiling of Pooled Genetic Screens. Dixit A, Parnas O, Li B, Chen J, Fulco CP, Jerby-Arnon L, Marjanovic ND, Dionne D, Burks T, Raychowdhury R, Adamson B, Norman TM, Lander ES, Weissman JS, Friedman N, Regev A. Cell. pubmed:27984732;  doi:10.1016/j.cell.2016.11.038

35. LTE1 promotes Exit from Mitosis by multiple mechanisms. Falk JE, Campbell IW, Joyce K, Whalen J, Seshan A, Amon A. Mol Biol Cell. pubmed:27798238;  doi:10.1091/mbc.E16-08-0563

36. Suppression of 19S proteasome subunits marks emergence of an altered cell state in diverse cancers. Tsvetkov P, Sokol E, Jin D, Brune Z, Thiru P, Ghandi M, Garraway LA, Gupta PB, Santagata S, Whitesell L, Lindquist S. Proc Natl Acad Sci U S A. pubmed:28028240;  doi:10.1073/pnas.1619067114

37. ERK and p38 MAPK Activities Determine Sensitivity to PI3K/mTOR Inhibition via Regulation of MYC and YAP. Muranen T, Selfors LM, Hwang J, Gallegos LL, Coloff JL, Thoreen CC, Kang SA, Sabatini DM, Mills GB, Brugge JS. Cancer Res. pubmed:27913436;  doi:10.1158/0008-5472.CAN-16-0155

38. PKM2, cancer metabolism, and the road ahead. Dayton TL, Jacks T, Vander Heiden MG. EMBO Rep. pubmed:27856534;  doi:10.15252/embr.201643300

39. The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells. Beyaz S, Kim JH, Pinello L, Xifaras ME, Hu Y, Huang J, Kerenyi MA, Das PP, Barnitz RA, Herault A, Dogum R, Haining WN, Yilmaz OH, Passegue E, Yuan GC, Orkin SH, Winau F. Nat Immunol. pubmed:27992400;  doi:10.1038/ni.3644

40. Molecular Pathways: Dietary regulation of stemness and tumor initiation by the PPAR-delta pathway. Yilmaz OH, Beyaz S. Clin Cancer Res. pubmed:27702819;  doi:10.1158/1078-0432.CCR-16-0775

41. 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