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: July 2017

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1. An engineering design approach to systems biology. Janes KA, Chandran PL, Ford RM, Lazzara MJ, Papin JA, Peirce SM, Saucerman JJ, Lauffenburger DA. Integr Biol (Camb)pubmed:28590470;  doi:10.1039/c7ib00014f

2. 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

3. An engineered protein antagonist of K-Ras/B-Raf interaction. Kauke MJ, Traxlmayr MW, Parker JA, Kiefer JD, Knihtila R, McGee J, Verdine G, Mattos C, Wittrup KD. Sci Reppubmed:28724936;  doi:10.1038/s41598-017-05889-7

4. The proline rich domain of p53 is dispensable for MGMT-dependent DNA repair and cell survival following alkylation damage. Baran K, Yang M, Dillon CP, Samson LL, Green DR. Cell Death Differpubmed:28753207;  doi:10.1038/cdd.2017.116

5. ALKBH7 drives a tissue and sex-specific necrotic cell death response following alkylation-induced damage. Jordan JJ, Chhim S, Margulies CM, Allocca M, Bronson RT, Klungland A, Samson LD, Fu D. Cell Death Dispubmed:28726787;  doi:10.1038/cddis.2017.343

6. Camptothecin resistance is determined by the regulation of topoisomerase I degradation mediated by ubiquitin proteasome pathway. Ando K, Shah AK, Sachdev V, Kleinstiver BP, Taylor-Parker J, Welch MM, Hu Y, Salgia R, White FM, Parvin JD, Ozonoff A, Rameh LE, Joung JK, Bharti AK. Oncotargetpubmed:28415827;  doi:10.18632/oncotarget.16376

7. In situ expansion of engineered human liver tissue in a mouse model of chronic liver disease. Stevens KR, Scull MA, Ramanan V, Fortin CL, Chaturvedi RR, Knouse KA, Xiao JW, Fung C, Mirabella T, Chen AX, McCue MG, Yang MT, Fleming HE, Chung K, de Jong YP, Chen CS, Rice CM, Bhatia SN. Sci Transl Medpubmed:28724577;  doi:10.1126/scitranslmed.aah5505

8. Porous Silicon Nanoparticle Delivery of Tandem Peptide Anti-Infectives for the Treatment of Pseudomonas aeruginosa Lung Infections. Kwon EJ, Skalak M, Bertucci A, Braun G, Ricci F, Ruoslahti E, Sailor MJ, Bhatia SN. Adv Materpubmed:28699173;  doi:10.1002/adma.201701527

9. Integrated Gut and Liver Microphysiological Systems for Quantitative In Vitro Pharmacokinetic Studies. Tsamandouras N, Chen WLK, Edington CD, Stokes CL, Griffith LG, Cirit M. AAPS Jpubmed:28752430;  doi:10.1208/s12248-017-0122-4

10. 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

11. Integrated assessment of diclofenac biotransformation, pharmacokinetics, and omics-based toxicity in a 3D human liver-immunocompetent co-culture system. Sarkar U, Ravindra KC, Large E, Young CL, Rivera-Burgos D, Yu J, Cirit M, Hughes DJ, Wishnok JS, Lauffenburger DA, Griffith LG, Tannenbaum SR. Drug Metab Dispospubmed:28450578;  doi:10.1124/dmd.116.074005

12. Polymer conjugated retinoids for controlled transdermal delivery. Castleberry SA, Quadir MA, Sharkh MA, Shopsowitz KE, Hammond PT. J Control Releasepubmed:28690160;  doi:10.1016/j.jconrel.2017.07.003

13. Ligand-decorated click polypeptide derived nanoparticles for targeted drug delivery applications. Quadir MA, Morton SW, Mensah LB, Shopsowitz K, Dobbelaar J, Effenberger N, Hammond PT. Nanomedicinepubmed:28263813;  doi:10.1016/j.nano.2017.02.010

14. Triggerable tough hydrogels for gastric resident dosage forms. Liu J, Pang Y, Zhang S, Cleveland C, Yin X, Booth L, Lin J, Lucy Lee YA, Mazdiyasni H, Saxton S, Kirtane AR, Erlach TV, Rogner J, Langer R, Traverso G. Nat Communpubmed:28743858;  doi:10.1038/s41467-017-00144-z

15. Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression. Yu D, Khan OF, Suva ML, Dong B, Panek WK, Xiao T, Wu M, Han Y, Ahmed AU, Balyasnikova IV, Zhang HF, Sun C, Langer R, Anderson DG, Lesniak MS. Proc Natl Acad Sci U S Apubmed:28696296;  doi:10.1073/pnas.1701911114

16. Synthesis and Biological Evaluation of Ionizable Lipid Materials for the In Vivo Delivery of Messenger RNA to B Lymphocytes. Fenton OS, Kauffman KJ, Kaczmarek JC, McClellan RL, Jhunjhunwala S, Tibbitt MW, Zeng MD, Appel EA, Dorkin JR, Mir FF, Yang JH, Oberli MA, Heartlein MW, DeRosa F, Langer R, Anderson DG. Adv Materpubmed:28681930;  doi:10.1002/adma.201606944

17. Nanoparticle-based drug delivery systems: a commercial and regulatory outlook as the field matures. Ragelle H, Danhier F, Preat V, Langer R, Anderson DG. Expert Opin Drug Delivpubmed:27730820;  doi:10.1080/17425247.2016.1244187

18. 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

19. Mechanistic action of weak acid drugs on biofilms. Kundukad B, Schussman M, Yang K, Seviour T, Yang L, Rice SA, Kjelleberg S, Doyle PS. Sci Reppubmed:28684849;  doi:10.1038/s41598-017-05178-3

20. Diverse Supramolecular Nanofiber Networks Assembled by Functional Low-Complexity Domains. An B, Wang X, Cui M, Gui X, Mao X, Liu Y, Li K, Chu C, Pu J, Ren S, Wang Y, Zhong G, Lu TK, Liu C, Zhong C. ACS Nanopubmed:28609612;  doi:10.1021/acsnano.7b02298

21. Early tumor detection afforded by in vivo imaging of near-infrared II fluorescence. Tao Z, Dang X, Huang X, Muzumdar MD, Xu ES, Bardhan NM, Song H, Qi R, Yu Y, Li T, Wei W, Wyckoff J, Birrer MJ, Belcher AM, Ghoroghchian PP. Biomaterialspubmed:28482280;  doi:10.1016/j.biomaterials.2017.04.046

22. A General Route for Nanoemulsion Synthesis Using Low-Energy Methods at Constant Temperature. Gupta A, Badruddoza AZM, Doyle PS. Langmuirpubmed:28654749;  doi:10.1021/acs.langmuir.7b01104

23. Pulsatility and high shear stress deteriorate barrier phenotype in brain microvascular endothelium. Garcia-Polite F, Martorell J, Del Rey-Puech P, Melgar-Lesmes P, O'Brien CC, Roquer J, Ois A, Principe A, Edelman ER, Balcells M. J Cereb Blood Flow Metabpubmed:27702879;  doi:10.1177/0271678X16672482

24. Ovarian cancer spheroid shrinkage following continuous exposure to cisplatin is a function of spheroid diameter. Tanenbaum LM, Mantzavinou A, Subramanyam KS, Del Carmen MG, Cima MJ. Gynecol Oncolpubmed:28499648;  doi:10.1016/j.ygyno.2017.04.014

25. Tet1 in Nucleus Accumbens Opposes Depression- and Anxiety-Like Behaviors. Feng J, Pena CJ, Purushothaman I, Engmann O, Walker D, Brown AN, Issler O, Doyle M, Harrigan E, Mouzon E, Vialou V, Shen L, Dawlaty MM, Jaenisch R, Nestler EJ. Neuropsychopharmacologypubmed:28074830;  doi:10.1038/npp.2017.6

26. An immunogenic personal neoantigen vaccine for patients with melanoma. Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, Zhang W, Luoma A, Giobbie-Hurder A, Peter L, Chen C, Olive O, Carter TA, Li S, Lieb DJ, Eisenhaure T, Gjini E, Stevens J, Lane WJ, Javeri I, Nellaiappan K, Salazar AM, Daley H, Seaman M, Buchbinder EI, Yoon CH, Harden M, Lennon N, Gabriel S, Rodig SJ, Barouch DH, Aster JC, Getz G, Wucherpfennig K, Neuberg D, Ritz J, Lander ES, Fritsch EF, Hacohen N, Wu CJ. Naturepubmed:28678778;  doi:10.1038/nature22991

27. Recurrent and functional regulatory mutations in breast cancer. Rheinbay E, Parasuraman P, Grimsby J, Tiao G, Engreitz JM, Kim J, Lawrence MS, Taylor-Weiner A, Rodriguez-Cuevas S, Rosenberg M, Hess J, Stewart C, Maruvka YE, Stojanov P, Cortes ML, Seepo S, Cibulskis C, Tracy A, Pugh TJ, Lee J, Zheng Z, Ellisen LW, Iafrate AJ, Boehm JS, Gabriel SB, Meyerson M, Golub TR, Baselga J, Hidalgo-Miranda A, Shioda T, Bernards A, Lander ES, Getz G. Naturepubmed:28658208;  doi:10.1038/nature22992

28. Monoclonal Invariant NKT (iNKT) Cell Mice Reveal a Role for Both Tissue of Origin and the TCR in Development of iNKT Functional Subsets. Clancy-Thompson E, Chen GZ, Tyler PM, Servos MM, Barisa M, Brennan PJ, Ploegh HL, Dougan SK. J Immunolpubmed:28576977;  doi:10.4049/jimmunol.1700214

29. AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia. Zhou F, Liu Y, Rohde C, Pauli C, Gerloff D, Kohn M, Misiak D, Baumer N, Cui C, Gollner S, Oellerich T, Serve H, Garcia-Cuellar MP, Slany R, Maciejewski JP, Przychodzen B, Seliger B, Klein HU, Bartenhagen C, Berdel WE, Dugas M, Taketo MM, Farouq D, Schwartz S, Regev A, Hebert J, Sauvageau G, Pabst C, Huttelmaier S, Muller-Tidow C. Nat Cell Biolpubmed:28650479;  doi:10.1038/ncb3563

30. Serum Metabolomics Investigation of Humanized Mouse Model with Dengue Infection. Cui L, Hou J, Fang J, Lee YH, Costa VV, Wong LH, Chen Q, Ooi EE, Tannenbaum SR, Chen J, Ong CN. J Virolpubmed:28468882;  doi:10.1128/JVI.00386-17

31. The awakening of the CDK10/Cyclin M protein kinase. Guen VJ, Gamble C, Lees JA, Colas P. Oncotargetpubmed:28178678;  doi:10.18632/oncotarget.15024

32. Presumptive TRP channel CED-11 promotes cell volume decrease and facilitates degradation of apoptotic cells in Caenorhabditis elegans. Driscoll K, Stanfield GM, Droste R, Horvitz HR. Proc Natl Acad Sci U S Apubmed:28760991;  doi:10.1073/pnas.1705084114

33. Cytoplasmic E2f4 forms organizing centres for initiation of centriole amplification during multiciliogenesis. Mori M, Hazan R, Danielian PS, Mahoney JE, Li H, Lu J, Miller ES, Zhu X, Lees JA, Cardoso WV. Nat Communpubmed:28675157;  doi:10.1038/ncomms15857

34. Dihydropyrimidine-thiones and clioquinol synergize to target beta-amyloid cellular pathologies through a metal-dependent mechanism. Tardiff DF, Brown LE, Yan X, Trilles R, Jui NT, Barrasa MI, Caldwell KA, Caldwell GA, Schaus SE, Lindquist S. ACS Chem Neuroscipubmed:28628299;  doi:10.1021/acschemneuro.7b00187

35. Quantitative proteomics identify Tenascin-C as a promoter of lung cancer progression and contributor to a signature prognostic of patient survival. Gocheva V, Naba A, Bhutkar A, Guardia T, Miller KM, Li CM, Dayton TL, Sanchez-Rivera FJ, Kim-Kiselak C, Jailkhani N, Winslow MM, Del Rosario A, Hynes RO, Jacks T. Proc Natl Acad Sci U S Apubmed:28652369;  doi:10.1073/pnas.1707054114

36. 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

37. Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. Olivares O, Mayers JR, Gouirand V, Torrence ME, Gicquel T, Borge L, Lac S, Roques J, Lavaut MN, Berthezene P, Rubis M, Secq V, Garcia S, Moutardier V, Lombardo D, Iovanna JL, Tomasini R, Guillaumond F, Vander Heiden MG, Vasseur S. Nat Communpubmed:28685754;  doi:10.1038/ncomms16031

38. Drugs, Bugs, and Cancer: Fusobacterium nucleatum Promotes Chemoresistance in Colorectal Cancer. Ramos A, Hemann MT. Cellpubmed:28753421;  doi:10.1016/j.cell.2017.07.018

39. Transcription elongation factors represent in vivo cancer dependencies in glioblastoma. Miller TE, Liau BB, Wallace LC, Morton AR, Xie Q, Dixit D, Factor DC, Kim LJY, Morrow JJ, Wu Q, Mack SC, Hubert CG, Gillespie SM, Flavahan WA, Hoffmann T, Thummalapalli R, Hemann MT, Paddison PJ, Horbinski CM, Zuber J, Scacheri PC, Bernstein BE, Tesar PJ, Rich JN. Naturepubmed:28678782;  doi:10.1038/nature23000

40. Induction of necroptosis in cancer stem cells by a nickel(II)-dithiocarbamate phenanthroline complex. Flamme M, Cressey P, Lu C, Bruno P, Eskandari A, Hemann M, Hogarth G, Suntharalingam K. Chemistrypubmed:28556445;  doi:10.1002/chem.201701837

41. CF2H, a Hydrogen Bond Donor. Sessler CD, Rahm M, Becker S, Goldberg JM, Wang F, Lippard SJ. J Am Chem Socpubmed:28576078;  doi:10.1021/jacs.7b04457

42. Identification of Small Molecule Translesion Synthesis Inhibitors That Target the Rev1-CT/RIR Protein-Protein Interaction. Sail V, Rizzo AA, Chatterjee N, Dash RC, Ozen Z, Walker GC, Korzhnev DM, Hadden MK. ACS Chem Biolpubmed:28541665;  doi:10.1021/acschembio.6b01144

43. Upholding a role for EMT in pancreatic cancer metastasis. Aiello NM, Brabletz T, Kang Y, Nieto MA, Weinberg RA, Stanger BZ. Naturepubmed:28682339;  doi:10.1038/nature22963

44. Upholding a role for EMT in breast cancer metastasis. Ye X, Brabletz T, Kang Y, Longmore GD, Nieto MA, Stanger BZ, Yang J, Weinberg RA. Naturepubmed:28682326;  doi:10.1038/nature22816