Publications
LSP Bibliography
2576724
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1
national-library-of-medicine-grant-proposals
50
date
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year
1
2179
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1.
Mollaoglu G, Tepper A, Falcomatà C, Potak HT, Pia L, Amabile A, Mateus-Tique J, Rabinovich N, Park MD, LaMarche NM, Brody R, Browning L, Lin JR, Zamarin D, Sorger PK, Santagata S, Merad M, Baccarini A, Brown BD. Ovarian cancer-derived IL-4 promotes immunotherapy resistance. Cell. 2024 Oct 25;S0092-8674(24)01154–1. PMID: 39481380
1.
Lu D, Faizi M, Drown B, Simerzin A, François J, Bradshaw G, Kelleher N, Jambhekar A, Gunawardena J, Lahav G. Temporal regulation of gene expression through integration of p53 dynamics and modifications. Sci Adv. 2024 Oct 25;10(43):eadp2229. PMCID: PMC11506164
1.
Stojanovic L, Abbotts R, Tripathi K, Coon CM, Rajendran S, Farid EA, Hostetter G, Guarnieri JW, Wallace DC, Liu S, Wan J, Calendo G, Marker R, Gohari Z, Inayatullah MMA, Tiwari VK, Kader T, Santagata S, Drapkin R, Kommoss S, Pfisterer J, Konecny GE, Coopergard R, Issa JP, Winterhoff BJN, Topper MJ, Sandusky GE, Miller KD, Baylin SB, Nephew KP, Rassool FV. ZNFX1 is a Novel Master Regulator in Epigenetically-induced Pathogen Mimicry and Inflammasome Signaling in Cancer. bioRxiv. 2024 Oct 21;2024.10.18.618659. PMCID: PMC11526927
1.
Schade AE, Perurena N, Yang Y, Rodriguez CL, Krishnan A, Gardner A, Loi P, Xu Y, Nguyen VTM, Mastellone GM, Pilla NF, Watanabe M, Ota K, Davis RA, Mattioli K, Xiang D, Zoeller JJ, Lin JR, Morganti S, Garrido-Castro AC, Tolaney SM, Li Z, Barbie DA, Sorger PK, Helin K, Santagata S, Knott SRV, Cichowski K. AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution. Nature. 2024 Oct 9; PMID: 39385030
1.
Ji W, Du G, Jiang J, Lu W, Mills CE, Yuan L, Jiang F, He Z, Bradshaw GA, Chung M, Jiang Z, Byun WS, Hinshaw SM, Zhang T, Gray NS. Discovery of bivalent small molecule degraders of cyclin-dependent kinase 7 (CDK7). Eur J Med Chem. 2024 Oct 5;276:116613. PMCID: PMC11316633
1.
Kader T, Lin JR, Hug C, Coy S, Chen YA, de Bruijn I, Shih N, Jung E, Pelletier RJ, Leon ML, Mingo G, Omran DK, Lee JS, Yapp C, Satravada BA, Kundra R, Xu Y, Chan S, Tefft JB, Muhlich J, Kim S, Gysler SM, Agudo J, Heath JR, Schultz N, Drescher C, Sorger PK, Drapkin R, Santagata S. Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma. bioRxiv; 2024. PMCID: PMC11463462
1.
Wala J, de Bruijn I, Coy S, Gagné A, Chan S, Chen YA, Hoffer J, Muhlich J, Schultz N, Santagata S, Sorger PK. Integrating spatial profiles and cancer genomics to identify immune-infiltrated mismatch repair proficient colorectal cancers. bioRxiv; 2024. PMCID: PMC11463659
1.
Minichetti DG, Boyd A, Lemire E, Hacker J, Haber AL, Roditi RE, Albers MW, Lee S, Buchheit KM, Laidlaw TM, Bankova LG. Determinants of Persistence and Recovery of Chronic COVID19 Chemosensory Dysfunction. J Allergy Clin Immunol. 2024 Sep 11;S0091-6749(24)00913–8. PMID: 39270802
1.
Ghosh HS, Patel RV, Woodward E, Greenwald NF, Bhave VM, Maury EA, Cello G, Hoffman SE, Li Y, Gupta H, Youssef G, Spurr LF, Vogelzang J, Touat M, Dubois F, Cherniack AD, Guo X, Tavakol S, Cioffi G, Lindeman NI, Ligon AH, Chiocca EA, Reardon DA, Wen PY, Meredith D, Santagata S, Barnholtz-Sloan JS, Ligon KL, Beroukhim R, Bi WL. Contemporary Prognostic Signatures and Refined Risk Stratification of Gliomas: An Analysis of 4,400 Tumors. Neuro Oncol. 2024 Aug 21;noae164. PMID: 39164213
1.
Do BT, Hsu PP, Vermeulen SY, Wang Z, Hirz T, Abbott KL, Aziz N, Replogle JM, Bjelosevic S, Paolino J, Nelson SA, Block S, Darnell AM, Ferreira R, Zhang H, Milosevic J, Schmidt DR, Chidley C, Harris IS, Weissman JS, Pikman Y, Stegmaier K, Cheloufi S, Su XA, Sykes DB, Vander Heiden MG. Nucleotide depletion promotes cell fate transitions by inducing DNA replication stress. Dev Cell. 2024 Aug 19;59(16):2203-2221.e15. PMID: 38823395
1.
Souque C, González Ojeda I, Baym M. From Petri Dishes to Patients to Populations: Scales and Evolutionary Mechanisms Driving Antibiotic Resistance. Annu Rev Microbiol [Internet]. 2024 Aug 14; Available from: https://www.annualreviews.org/content/journals/10.1146/annurev-micro-041522-102707 PMID: 39141706
1.
Loi P, Schade AE, Rodriguez CL, Krishnan A, Perurena N, Nguyen VTM, Xu Y, Watanabe M, Davis RA, Gardner A, Pilla NF, Mattioli K, Popow O, Gunduz N, Lannagan TRM, Fitzgerald S, Sicinska ET, Lin JR, Tan W, Brais LK, Haigis KM, Giannakis M, Ng K, Santagata S, Helin K, Sansom OJ, Cichowski K. Epigenetic and oncogenic inhibitors cooperatively drive differentiation and kill KRAS-mutant colorectal cancers. Cancer Discov. 2024 Aug 12; PMID: 39121480
1.
Sarfraz I, Wang Y, Shastry A, Teh WK, Sokolov A, Herb BR, Creasy HH, Virshup I, Dries R, Degatano K, Mahurkar A, Schnell DJ, Madrigal P, Hilton J, Gehlenborg N, Tickle T, Campbell JD. MAMS: matrix and analysis metadata standards to facilitate harmonization and reproducibility of single-cell data. Genome Biol. 2024 Aug 1;25(1):205. PMCID: PMC11292877
1.
Maliga Z, Kim DY, Bui ATN, Lin JR, Dewan AK, Jadeja S, Murphy GF, Nirmal AJ, Lian CG, Sorger PK, LeBoeuf NR. Immune Profiling of Dermatologic Adverse Events from Checkpoint Blockade Using Tissue Cyclic Immunofluorescence: A Pilot Study. J Invest Dermatol. 2024 Aug;144(8):1887-1890.e5. PMID: 38360200
1.
Ahdritz G, Bouatta N, Floristean C, Kadyan S, Xia Q, Gerecke W, O’Donnell TJ, Berenberg D, Fisk I, Zanichelli N, Zhang B, Nowaczynski A, Wang B, Stepniewska-Dziubinska MM, Zhang S, Ojewole A, Guney ME, Biderman S, Watkins AM, Ra S, Lorenzo PR, Nivon L, Weitzner B, Ban YEA, Chen S, Zhang M, Li C, Song SL, He Y, Sorger PK, Mostaque E, Zhang Z, Bonneau R, AlQuraishi M. OpenFold: retraining AlphaFold2 yields new insights into its learning mechanisms and capacity for generalization. Nat Methods. 2024 Aug;21(8):1514–1524. PMID: 38744917
1.
Conger KO, Chidley C, Ozgurses ME, Zhao H, Kim Y, Semina SE, Burns P, Rawat V, Lietuvninkas L, Sheldon R, Ben-Sahra I, Frasor J, Sorger PK, DeNicola GM, Coloff JL. ASCT2 is a major contributor to serine uptake in cancer cells. Cell Rep. 2024 Jul 26;43(8):114552. PMID: 39068660
1.
Fang R, Vallius T, Zhang A, Van Cura D, Alicandri F, Fischer G, Draper E, Xu S, Pelletier R, Katsyv I, Sorger PK, Murphy GF, Lian CG. PRAME expression in melanoma is negatively regulated by TET2-mediated DNA hydroxymethylation [Internet]. bioRxiv; 2024. Available from: http://biorxiv.org/lookup/doi/10.1101/2024.07.26.605293 PMCID: PMC11291125
1.
De Bruijn I, Nikolov M, Lau C, Clayton A, Gibbs DL, Mitraka E, Pozhidayeva D, Lash A, Sumer SO, Altreuter J, Anton K, DeFelice M, Li X, Lisman A, R Longabaugh WJ, Muhlich J, Santagata S, Nandakumar S, Sorger PK, Suver C, Schultz N, Taylor AJ, Thorsson V, Cerami E, Eddy JA. Sharing Data from the Human Tumor Atlas Network through Standards, Infrastructure, and Community Engagement. bioRxiv; 2024.
1.
Warchol S, Troidl J, Muhlich J, Krueger R, Hoffer J, Lin T, Beyer J, Glassman E, Sorger P, Pfister H. psudo: Exploring Multi‐Channel Biomedical Image Data with Spatially and Perceptually Optimized Pseudocoloring. Computer Graphics Forum. 2024 Jun 10;e15103.
1.
Grinshpun A, Russo D, Ma W, Verma A, Hermida-Prado F, Sherman S, Gaglia G, Kabraji S, Kirkner G, Hughes ME, Lin NU, Sandusky Z, Nardone A, Guarducci C, Nguyen QD, Santagata S, Nagy Z, Jeselsohn R. Pure estrogen receptor antagonists potentiate capecitabine activity in ESR1-mutant breast cancer. NPJ Breast Cancer. 2024 Jun 8;10(1):42. PMCID: PMC11162492
1.
Susa KJ, Bradshaw GA, Eisert RJ, Schilling CM, Kalocsay M, Blacklow SC, Kruse AC. A spatiotemporal map of co-receptor signaling networks underlying B cell activation. Cell Rep. 2024 Jun 7;43(6):114332. PMID: 38850533
1.
König LE, Rodriguez S, Hug C, Daneshvari S, Chung A, Bradshaw GA, Sahin A, Zhou G, Eisert RJ, Piccioni F, Das S, Kalocsay M, Sokolov A, Sorger P, Root DE, Albers MW. TYK2 as a novel therapeutic target in Alzheimer’s Disease with TDP-43 inclusions. bioRxiv; 2024.
1.
Deng X, Seguinot BO, Bradshaw G, Lee JS, Coy S, Kalocsay M, Santagata S, Mitchison T. STMND1 is a phylogenetically ancient stathmin which localizes to motile cilia and exhibits nuclear translocation that is inhibited when soluble tubulin concentration increases. Mol Biol Cell. 2024 Jun 1;35(6):ar82. PMCID: PMC11238091
1.
Nirmal AJ, Sorger PK. SCIMAP: A Python Toolkit for Integrated Spatial Analysis of Multiplexed Imaging Data. J Open Source Softw. 2024 May 29;9(97):6604. PMCID: PMC11173324
1.
Jain A, Gyori BM, Hakim S, Jain A, Sun L, Petrova V, Bhuiyan SA, Zhen S, Wang Q, Kawaguchi R, Bunga S, Taub DG, Ruiz-Cantero MC, Tong-Li C, Andrews N, Kotoda M, Renthal W, Sorger PK, Woolf CJ. Nociceptor-immune interactomes reveal insult-specific immune signatures of pain. Nat Immunol. 2024 May 28; PMID: 38806708
1.
Zhou FY, Yapp C, Shang Z, Daetwyler S, Marin Z, Islam MT, Nanes BA, Jenkins E, Gihana GM, Chang BJ, Weems A, Dustin M, Morrison SJ, Fiolka RP, Dean KM, Jamieson A, Sorger PK, Danuser GK. A general algorithm for consensus 3D cell segmentation from 2D segmented stacks [Internet]. bioRxiv; 2024 [cited 2024 Oct 1]. Available from: http://biorxiv.org/lookup/doi/10.1101/2024.05.03.592249 PMCID: PMC11100681
1.
Gallo PN, Mihelc E, Eisert R, Bradshaw GA, Dimek F, Leffler A, Kalocsay M, Moiseenkova-Bell V. The dynamic TRPV2 ion channel proximity proteome reveals functional links of calcium flux with cellular adhesion factors NCAM and L1CAM in neurite outgrowth. Cell Calcium. 2024 May 4;121:102894. PMID: 38728789
1.
Olesinski EA, Bhatia KS, Wang C, Pioso MS, Lin XX, Mamdouh AM, Ng SX, Sandhu V, Jasdanwala SS, Yilma B, Bohl S, Ryan JA, Malani D, Luskin MR, Kallioniemi O, Porkka K, Adamia S, Chng WJ, Osato M, Weinstock DM, Garcia JS, Letai A, Bhatt S. Acquired Multidrug Resistance in AML Is Caused by Low Apoptotic Priming in Relapsed Myeloblasts. Blood Cancer Discov. 2024 May 1;5(3):180–201. PMCID: PMC11061585
1.
Chidley C, Darnell AM, Gaudio BL, Lien EC, Barbeau AM, Vander Heiden MG, Sorger PK. A CRISPRi/a screening platform to study cellular nutrient transport in diverse microenvironments. Nat Cell Biol. 2024 May;26(5):825–838. PMCID: PMC11098743
1.
Sutcliffe SG, Kraemer SA, Ellmen I, Knapp JJ, Overton AK, Nash D, Nissimov JI, Charles TC, Dreifuss D, Topolsky I, Baykal PI, Fuhrmann L, Jablonski KP, Beerenwinkel N, Levy JI, Olabode AS, Becker DG, Gugan G, Brintnell E, Poon AFY, Valieris R, Drummond RD, Defelicibus A, Dias-Neto E, Rosales RA, Tojal da Silva I, Orfanou A, Psomopoulos F, Pechlivanis N, Pipes L, Chen Z, Baaijens JA, Baym M, Shapiro BJ. Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data. Microb Genom. 2024 May;10(5). PMID: 38785221
1.
Ke S, Dang F, Wang L, Chen JY, Naik MT, Li W, Thavamani A, Kim N, Naik NM, Sui H, Tang W, Qiu C, Koikawa K, Batalini F, Stern Gatof E, Isaza DA, Patel JM, Wang X, Clohessy JG, Heng YJ, Lahav G, Liu Y, Gray NS, Zhou XZ, Wei W, Wulf GM, Lu KP. Reciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry. Nat Commun. 2024 Apr 15;15(1):3220. PMCID: PMC11018817
1.
Quinones-Olvera N, Owen SV, McCully LM, Marin MG, Rand EA, Fan AC, Martins Dosumu OJ, Paul K, Sanchez Castaño CE, Petherbridge R, Paull JS, Baym M. Diverse and abundant phages exploit conjugative plasmids. Nat Commun. 2024 Apr 12;15(1):3197. PMCID: PMC11015023
1.
Tobochnik S, Regan MS, Dorotan MKC, Reich D, Lapinskas E, Hossain MA, Stopka S, Santagata S, Murphy MM, Arnaout O, Bi WL, Chiocca EA, Golby AJ, Mooney MA, Smith TR, Ligon KL, Wen PY, Agar NYR, Lee JW. Pilot trial of perampanel on peritumoral hyperexcitability and clinical outcomes in newly diagnosed high-grade glioma [Internet]. medRxiv; 2024 [cited 2024 Oct 11]. Available from: http://medrxiv.org/lookup/doi/10.1101/2024.04.11.24305666 PMCID: PMC11030478
1.
Callahan TJ, Tripodi IJ, Stefanski AL, Cappelletti L, Taneja SB, Wyrwa JM, Casiraghi E, Matentzoglu NA, Reese J, Silverstein JC, Hoyt CT, Boyce RD, Malec SA, Unni DR, Joachimiak MP, Robinson PN, Mungall CJ, Cavalleri E, Fontana T, Valentini G, Mesiti M, Gillenwater LA, Santangelo B, Vasilevsky NA, Hoehndorf R, Bennett TD, Ryan PB, Hripcsak G, Kahn MG, Bada M, Baumgartner WA, Hunter LE. An open source knowledge graph ecosystem for the life sciences. Sci Data. 2024 Apr 11;11(1):363. PMCID: PMC11009265
1.
Ricciuti B, Lamberti G, Puchala SR, Mahadevan NR, Lin JR, Alessi JV, Chowdhury A, Li YY, Wang X, Spurr L, Pecci F, Di Federico A, Venkatraman D, Barrichello AP, Gandhi M, Vaz VR, Pangilinan AJ, Haradon D, Lee E, Gupta H, Pfaff KL, Welsh EL, Nishino M, Cherniack AD, Johnson BE, Weirather JL, Dryg ID, Rodig SJ, Sholl LM, Sorger P, Santagata S, Umeton R, Awad MM. Genomic and Immunophenotypic Landscape of Acquired Resistance to PD-(L)1 Blockade in Non-Small-Cell Lung Cancer. J Clin Oncol. 2024 Apr 10;42(11):1311–1321. PMID: 38207230
1.
Pan RA, Wang Y, Qiu S, Villalobos-Ortiz M, Ryan J, Morris E, Halilovic E, Letai A. BH3 profiling as pharmacodynamic biomarker for the activity of BH3 mimetics. Haematologica. 2024 Apr 1;109(4):1253–1258. PMCID: PMC10985422
1.
Wan G, Maliga Z, Yan B, Vallius T, Shi Y, Khattab S, Chang C, Nirmal AJ, Yu KH, Liu D, Lian CG, DeSimone MS, Sorger PK, Semenov YR. SpatialCells: automated profiling of tumor microenvironments with spatially resolved multiplexed single-cell data. Brief Bioinform. 2024 Mar 27;25(3):bbae189. PMCID: PMC11066940
1.
Eschbacher KL, Tran QT, Moskalev EA, Jenkins S, Fritchie K, Stoehr R, Caron A, Link MJ, Brown PD, Guajardo A, Brat DJ, Wu A, Santagata S, Louis DN, Brastianos PK, Kaplan AB, Alexander B, Rossi S, Ferrarese F, Raleigh DR, Nguyen MP, Gross J, Velazquez Vega J, Rodriguez F, Perry A, Martinez-Lage M, Orr BA, Haller F, Giannini C. NAB2::STAT6 fusions and genome-wide DNA methylation profiling: Predictors of patient outcomes in meningeal solitary fibrous tumors. Brain Pathol. 2024 Mar 24;e13256. PMID: 38523251
1.
Launonen IM, Erkan EP, Niemiec I, Junquera A, Hincapié-Otero M, Afenteva D, Liang Z, Salko M, Szabo A, Perez-Villatoro F, Falco MM, Li Y, Micoli G, Nagaraj A, Haltia UM, Kahelin E, Oikkonen J, Hynninen J, Virtanen A, Nirmal AJ, Vallius T, Hautaniemi S, Sorger P, Vähärautio A, Färkkilä A. Chemotherapy induces myeloid-driven spatial T-cell exhaustion in ovarian cancer [Internet]. 2024 [cited 2024 Oct 11]. Available from: http://biorxiv.org/lookup/doi/10.1101/2024.03.19.585657 PMCID: PMC10983974
1.
Marques C, Held A, Dorfman K, Sung J, Song C, Kavuturu AS, Aguilar C, Russo T, Oakley DH, Albers MW, Hyman BT, Petrucelli L, Lagier-Tourenne C, Wainger BJ. Neuronal STING activation in amyotrophic lateral sclerosis and frontotemporal dementia. Acta Neuropathol. 2024 Mar 13;147(1):56. PMCID: PMC10937762
1.
De Los Angeles A, Hug CB, Gladyshev VN, Church GM, Velychko S. Sendai virus persistence questions the transient naive reprogramming method for iPSC generation [Internet]. bioRxiv; 2024. Available from: http://biorxiv.org/lookup/doi/10.1101/2024.03.07.583804 PMCID: PMC10979911
1.
Coy S, Lee JS, Chan SJ, Woo T, Jones J, Alexandrescu S, Wen PY, Sorger PK, Ligon KL, Santagata S. Systematic characterization of antibody-drug conjugate targets in central nervous system tumors. Neuro Oncol. 2024 Mar 4;26(3):458–472. PMCID: PMC10912007
1.
Gomez SM, Axtman AD, Willson TM, Major MB, Townsend RR, Sorger PK, Johnson GL. Illuminating function of the understudied druggable kinome. Drug Discov Today. 2024 Mar;29(3):103881. PMCID: PMC11262466
1.
Zhou I, Plana D, Palmer AC. Tumor-Specific Activity of Precision Medicines in the NCI-MATCH Trial. Clin Cancer Res. 2024 Feb 16;30(4):786–792. PMID: 38109210
1.
Bhola PD, Letai A. The Siren Song of Synergy. Blood Cancer Discov. 2024 Feb 8;OF1–OF2. PMID: 38331415
1.
Gritsch D, Santagata S, Brastianos PK. Integrating Systemic Therapies into the Multimodality Therapy of Patients with Craniopharyngioma. Curr Treat Options Oncol. 2024 Feb;25(2):261–273. PMID: 38300480
1.
Rogava M, Aprati TJ, Chi WY, Melms JC, Hug C, Davis SH, Earlie EM, Chung C, Deshmukh SK, Wu S, Sledge G, Tang S, Ho P, Amin AD, Caprio L, Gurjao C, Tagore S, Ngo B, Lee MJ, Zanetti G, Wang Y, Chen S, Ge W, Melo LMN, Allies G, Rösler J, Gibney GT, Schmitz OJ, Sykes M, Creusot RJ, Tüting T, Schadendorf D, Röcken M, Eigentler TK, Molotkov A, Mintz A, Bakhoum SF, Beyaz S, Cantley LC, Sorger PK, Meckelmann SW, Tasdogan A, Liu D, Laughney AM, Izar B. Loss of Pip4k2c confers liver-metastatic organotropism through insulin-dependent PI3K-AKT pathway activation. Nat Cancer. 2024 Jan 29; PMID: 38286827
1.
Couce A, Limdi A, Magnan M, Owen SV, Herren CM, Lenski RE, Tenaillon O, Baym M. Changing fitness effects of mutations through long-term bacterial evolution. Science. 2024 Jan 26;383(6681):eadd1417. PMID: 38271521
1.
Zhang X, Pant SM, Ritch CC, Tang HY, Shao H, Dweep H, Gong YY, Brooks R, Brafford P, Wolpaw AJ, Lee Y, Weeraratna A, Sehgal A, Herlyn M, Kossenkov A, Speicher D, Sorger PK, Santagata S, Dang CV. Cell state dependent effects of Bmal1 on melanoma immunity and tumorigenicity. Nat Commun. 2024 Jan 20;15(1):633. PMCID: PMC10799901
1.
Guerriero JL, Lin JR, Pastorello RG, Du Z, Chen YA, Townsend MG, Shimada K, Hughes ME, Ren S, Tayob N, Zheng K, Mei S, Patterson A, Taneja KL, Metzger O, Tolaney SM, Lin NU, Dillon DA, Schnitt SJ, Sorger PK, Mittendorf EA, Santagata S. Qualification of a multiplexed tissue imaging assay and detection of novel patterns of HER2 heterogeneity in breast cancer. NPJ Breast Cancer. 2024 Jan 2;10(1):2. PMCID: PMC10761880