Photo of Peter Sorger,  PhD

Peter Sorger, PhD

Harvard Medical School

Harvard Medical School

Peter Sorger, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Otto Krayer Professor of Systems Pharmacology, Systems Biology, Harvard Medical School
  • Head of Program, Harvard Program in Therapeutic Science, Harvard Medical School
  • Founding Director, Laboratory of Systems Pharmacology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

As head of the Harvard Program in Therapeutic Sciences, Sorger leads a university-wide effort to advance the basic and translational science used to develop new medicines, identify responsive patients and evaluate new drugs via precision clinical trials. The Laboratory of Systems Pharmacology he directs brings together 18 faculty members from six institutions in a multi-disciplinary effort to develop and apply new concepts in drug discovery. Sorger was cofounder of Merrimack Pharmaceuticals and Glencoe Software and is an advisor to multiple public and private companies and research institutes in the US, Europe and Japan. He is also active as a teacher, focusing on graduate-level courses in structural biology, physical chemistry and systems biology

Research in the Sorger Lab focuses on the systems biology of signal transduction and cell fate determination with an emphasis on inter- and intra-cellular signaling networks and their roles in controlling proliferation and cell death in cancer and inflammatory diseases. Our group uses mathematical and experimental approaches to model mechanisms of signal transduction and oncogenesis and then uses the models to understand and predict the responses of cells and tumors to therapeutic drugs applied individually and in combination. Our models aim to capture precise biochemical and oncogenic mechanism and also the complexities of interaction among competing and overlapping signaling cascades. We study oncogenic and pharmacological mechanism in cell lines, transgenic mice and primary human tumor cells using imaging proteomic and genomic approaches. We also develop open-source software for analyzing biological networks and participate in multiple collaborative programs working to improve computational biology methods. We are now attempting to build collaborative programs with physician-scientists engaged in early stage clinical trials as a means to apply systems pharmacology approaches to patient stratification and combination therapy.

Publications from Harvard Catalyst Profiles

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  • Rashid R, Chen YA, Hoffer J, Muhlich JL, Lin JR, Krueger R, Pfister H, Mitchell R, Santagata S, Sorger PK. Narrative online guides for the interpretation of digital-pathology images and tissue-atlas data. Nat Biomed Eng 2021. PubMed
  • Duraiswamy J, Turrini R, Minasyan A, Barras D, Crespo I, Grimm AJ, Casado J, Genolet R, Benedetti F, Wicky A, Ioannidou K, Castro W, Neal C, Moriot A, Renaud-Tissot S, Anstett V, Fahr N, Tanyi JL, Eiva MA, Jacobson CA, Montone KT, Westergaard MCW, Svane IM, Kandalaft LE, Delorenzi M, Sorger PK, Färkkilä A, Michielin O, Zoete V, Carmona SJ, Foukas PG, Powell DJ, Rusakiewicz S, Doucey MA, Dangaj Laniti D, Coukos G. Myeloid antigen-presenting cell niches sustain antitumor T cells and license PD-1 blockade via CD28 costimulation. Cancer Cell 2021. PubMed
  • Jessup J, Krueger R, Warchol S, Hoffer J, Muhlich J, Ritch CC, Gaglia G, Coy S, Chen YA, Lin JR, Santagata S, Sorger PK, Pfister H. Scope2Screen: Focus+Context Techniques for Pathology Tumor Assessment in Multivariate Image Data. IEEE Trans Vis Comput Graph 2021. PubMed
  • Liu D, Lin JR, Robitschek EJ, Kasumova GG, Heyde A, Shi A, Kraya A, Zhang G, Moll T, Frederick DT, Chen YA, Wang S, Schapiro D, Ho LL, Bi K, Sahu A, Mei S, Miao B, Sharova T, Alvarez-Breckenridge C, Stocking JH, Kim T, Fadden R, Lawrence D, Hoang MP, Cahill DP, Malehmir M, Nowak MA, Brastianos PK, Lian CG, Ruppin E, Izar B, Herlyn M, Van Allen EM, Nathanson K, Flaherty KT, Sullivan RJ, Kellis M, Sorger PK, Boland GM. Evolution of delayed resistance to immunotherapy in a melanoma responder. Nat Med 2021. PubMed
  • Jiang B, Gao Y, Che J, Lu W, Kaltheuner IH, Dries R, Kalocsay M, Berberich MJ, Jiang J, You I, Kwiatkowski N, Riching KM, Daniels DL, Sorger PK, Geyer M, Zhang T, Gray NS. Discovery and resistance mechanism of a selective CDK12 degrader. Nat Chem Biol 2021. PubMed
  • Keenan TE, Li T, Vallius T, Guerriero JL, Tayob N, Kochupurakkal B, Davis J, Pastorello R, Tahara RK, Anderson L, Conway J, He MX, Shannon E, Godin RE, Sorger PK, D'Andrea A, Overmoyer B, Winer EP, Mittendorf EA, Van Allen EM, Shapiro GI, Tolaney SM. Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer. Clin Cancer Res 2021; 27:983-991. PubMed
  • Ietswaart R, Gyori BM, Bachman JA, Sorger PK, Churchman LS. GeneWalk identifies relevant gene functions for a biological context using network representation learning. Genome Biol 2021; 22:55. PubMed
  • Färkkilä A, Rodríguez A, Oikkonen J, Gulhan DC, Nguyen H, Domínguez J, Ramos S, Mills CE, Perez-Villatoro F, Lazaro JB, Zhou J, Clairmont CS, Moreau LA, Park PJ, Sorger PK, Hautaniemi S, Frias S, D'Andrea AD. Heterogeneity and clonal evolution of acquired PARP inhibitor resistance in TP53- and BRCA1-deficient cells. Cancer Res 2021. PubMed
  • AlQuraishi M, Sorger PK. Differentiable biology: using deep learning for biophysics-based and data-driven modeling of molecular mechanisms. Nat Methods 2021; 18:1169-1180. PubMed
  • Mehta AK, Cheney EM, Hartl CA, Pantelidou C, Oliwa M, Castrillon JA, Lin JR, Hurst KE, de Oliveira Taveira M, Johnson NT, Oldham WM, Kalocsay M, Berberich MJ, Boswell SA, Kothari A, Johnson S, Dillon DA, Lipschitz M, Rodig S, Santagata S, Garber JE, Tung N, Yélamos J, Thaxton JE, Mittendorf EA, Sorger PK, Shapiro GI, Guerriero JL. Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer. 2021; 2:66-82. PubMed
  • Vemulapalli V, Chylek LA, Erickson A, Pfeiffer A, Gabriel KH, LaRochelle J, Subramanian K, Cao R, Stegmaier K, Mohseni M, LaMarche MJ, Acker MG, Sorger PK, Gygi SP, Blacklow SC. Time-resolved phosphoproteomics reveals scaffolding and catalysis-responsive patterns of SHP2-dependent signaling. Elife 2021. PubMed
  • Berginski ME, Moret N, Liu C, Goldfarb D, Sorger PK, Gomez SM. The Dark Kinase Knowledgebase: an online compendium of knowledge and experimental results of understudied kinases. Nucleic Acids Res 2021; 49:D529-D535. PubMed
  • Jerby-Arnon L, Neftel C, Shore ME, Weisman HR, Mathewson ND, McBride MJ, Haas B, Izar B, Volorio A, Boulay G, Cironi L, Richman AR, Broye LC, Gurski JM, Luo CC, Mylvaganam R, Nguyen L, Mei S, Melms JC, Georgescu C, Cohen O, Buendia-Buendia JE, Segerstolpe A, Sud M, Cuoco MS, Labes D, Gritsch S, Zollinger DR, Ortogero N, Beechem JM, Petur Nielsen G, Chebib I, Nguyen-Ngoc T, Montemurro M, Cote GM, Choy E, Letovanec I, Cherix S, Wagle N, Sorger PK, Haynes AB, Mullen JT, Stamenkovic I, Rivera MN, Kadoch C, Wucherpfennig KW, Rozenblatt-Rosen O, Suvà ML, Riggi N, Regev A. Opposing immune and genetic mechanisms shape oncogenic programs in synovial sarcoma. Nat Med 2021; 27:289-300. PubMed
  • Ringel AE, Drijvers JM, Baker GJ, Catozzi A, García-Cañaveras JC, Gassaway BM, Miller BC, Juneja VR, Nguyen TH, Joshi S, Yao CH, Yoon H, Sage PT, LaFleur MW, Trombley JD, Jacobson CA, Maliga Z, Gygi SP, Sorger PK, Rabinowitz JD, Sharpe AH, Haigis MC. Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity. Cell 2020; 183:1848-1866.e26. PubMed
  • Palmer AC, Plana D, Sorger PK. Comparing the Efficacy of Cancer Therapies between Subgroups in Basket Trials. Cell Syst 2020; 11:449-460.e2. PubMed
  • Magid SA, Jang WD, Schapiro D, Wei D, Tompkin J, Sorger PK, Pfister H. Channel Embedding for Informative Protein Identification from Highly Multiplexed Images. Med Image Comput Comput Assist Interv 2020; 12265:3-13. PubMed
  • Baker GJ, Muhlich JL, Palaniappan SK, Moore JK, Davis SH, Santagata S, Sorger PK. SYLARAS: A Platform for the Statistical Analysis and Visual Display of Systemic Immunoprofiling Data and Its Application to Glioblastoma. Cell Syst 2020; 11:272-285.e9. PubMed
  • Liu Y, Ferguson FM, Li L, Kuljanin M, Mills CE, Subramanian K, Harshbarger W, Gondi S, Wang J, Sorger PK, Mancias JD, Gray NS, Westover KD. Chemical Biology Toolkit for DCLK1 Reveals Connection to RNA Processing. Cell Chem Biol 2020. PubMed
  • Palmer AC, Plana D, Gao H, Korn JM, Yang G, Green J, Zhang X, Velazquez R, McLaughlin ME, Ruddy DA, Kowal C, Goldovitz J, Bullock C, Rivera S, Rakiec DP, Elliott G, Fordjour P, Meyer R, Loo A, Kurth E, Engelman JA, Bitter H, Sellers WR, Williams JA, Sorger PK. A proof of concept for biomarker-guided targeted therapy against ovarian cancer based on patient-derived tumor xenografts. Cancer Res 2020. PubMed
  • Zervantonakis IK, Poskus MD, Scott AL, Selfors LM, Lin JR, Dillon DA, Pathania S, Sorger PK, Mills GB, Brugge JS. Fibroblast-tumor cell signaling limits HER2 kinase therapy response via activation of MTOR and antiapoptotic pathways. Proc Natl Acad Sci U S A 2020. PubMed
  • Izar B, Tirosh I, Stover EH, Wakiro I, Cuoco MS, Alter I, Rodman C, Leeson R, Su MJ, Shah P, Iwanicki M, Walker SR, Kanodia A, Melms JC, Mei S, Lin JR, Porter CBM, Slyper M, Waldman J, Jerby-Arnon L, Ashenberg O, Brinker TJ, Mills C, Rogava M, Vigneau S, Sorger PK, Garraway LA, Konstantinopoulos PA, Liu JF, Matulonis U, Johnson BE, Rozenblatt-Rosen O, Rotem A, Regev A. A single-cell landscape of high-grade serous ovarian cancer. Nat Med 2020. PubMed
  • Teng M, Jiang J, He Z, Kwiatkowski NP, Donovan KA, Mills CE, Victor C, Hatcher JM, Fischer ES, Sorger PK, Zhang T, Gray NS. Development of CDK2 and CDK5 Dual Degrader TMX-2172. Angew Chem Int Ed Engl 2020. PubMed
  • Rozenblatt-Rosen O, Regev A, Oberdoerffer P, Nawy T, Hupalowska A, Rood JE, Ashenberg O, Cerami E, Coffey RJ, Demir E, Ding L, Esplin ED, Ford JM, Goecks J, Ghosh S, Gray JW, Guinney J, Hanlon SE, Hughes SK, Hwang ES, Iacobuzio-Donahue CA, Jané-Valbuena J, Johnson BE, Lau KS, Lively T, Mazzilli SA, Pe'er D, Santagata S, Shalek AK, Schapiro D, Snyder MP, Sorger PK, Spira AE, Srivastava S, Tan K, West RB, Williams EH, . The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution. Cell 2020; 181:236-249. PubMed
  • Schauer NJ, Liu X, Magin RS, Doherty LM, Chan WC, Ficarro SB, Hu W, Roberts RM, Iacob RE, Stolte B, Giacomelli AO, Perera S, McKay K, Boswell SA, Weisberg EL, Ray A, Chauhan D, Dhe-Paganon S, Anderson KC, Griffin JD, Li J, Hahn WC, Sorger PK, Engen JR, Stegmaier K, Marto JA, Buhrlage SJ. Selective USP7 inhibition elicits cancer cell killing through a p53-dependent mechanism. Sci Rep 2020; 10:5324. PubMed
  • Färkkilä A, Gulhan DC, Casado J, Jacobson CA, Nguyen H, Kochupurakkal B, Maliga Z, Yapp C, Chen YA, Schapiro D, Zhou Y, Graham JR, Dezube BJ, Munster P, Santagata S, Garcia E, Rodig S, Lako A, Chowdhury D, Shapiro GI, Matulonis UA, Park PJ, Hautaniemi S, Sorger PK, Swisher EM, D'Andrea AD, Konstantinopoulos PA. Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer. Nat Commun 2020; 11:1459. PubMed
  • Gaglia G, Rashid R, Yapp C, Joshi GN, Li CG, Lindquist SL, Sarosiek KA, Whitesell L, Sorger PK, Santagata S. HSF1 phase transition mediates stress adaptation and cell fate decisions. Nat Cell Biol 2020; 22:151-158. PubMed
  • Cunningham JM, Koytiger G, Sorger PK, AlQuraishi M. Biophysical prediction of protein-peptide interactions and signaling networks using machine learning. Nat Methods 2020; 17:175-183. PubMed
  • Lyashenko E, Niepel M, Dixit PD, Lim SK, Sorger PK, Vitkup D. Receptor-based mechanism of relative sensing and cell memory in mammalian signaling networks. Elife 2020. PubMed
  • Hoffer J, Rashid R, Muhlich JL, Chen YA, Russell DPW, Ruokonen J, Krueger R, Pfister H, Santagata S, Sorger PK. Minerva: a light-weight, narrative image browser for multiplexed tissue images. J Open Source Softw 2020. PubMed
  • Hemming ML, Nathenson MJ, Lin JR, Mei S, Du Z, Malik K, Marino-Enriquez A, Jagannathan JP, Sorger PK, Bertagnolli M, Sicinska E, Demetri GD, Santagata S. Response and mechanisms of resistance to larotrectinib and selitrectinib in metastatic undifferentiated sarcoma harboring oncogenic fusion of . JCO Precis Oncol 2020; 4:79-90. PubMed
  • Melms JC, Vallabhaneni S, Mills CE, Yapp C, Chen JY, Morelli E, Waszyk P, Kumar S, Deming D, Moret N, Rodriguez S, Subramanian K, Rogava M, Cartwright ANR, Luoma A, Mei S, Brinker TJ, Miller DM, Spektor A, Schadendorf D, Riggi N, Wucherpfennig KW, Sorger PK, Izar B. Inhibition of Haspin kinase promotes cell-intrinsic and extrinsic anti-tumor activity. Cancer Res 2019. PubMed
  • Rashid R, Gaglia G, Chen YA, Lin JR, Du Z, Maliga Z, Schapiro D, Yapp C, Muhlich J, Sokolov A, Sorger P, Santagata S. Highly multiplexed immunofluorescence images and single-cell data of immune markers in tonsil and lung cancer. Sci Data 2019; 6:323. PubMed
  • Chopra SS, Jenney A, Palmer A, Niepel M, Chung M, Mills C, Sivakumaren SC, Liu Q, Chen JY, Yapp C, Asara JM, Gray NS, Sorger PK. Torin2 Exploits Replication and Checkpoint Vulnerabilities to Cause Death of PI3K-Activated Triple-Negative Breast Cancer Cells. Cell Syst 2019. PubMed
  • Wang S, Lin JR, Sontag ED, Sorger PK. Inferring reaction network structure from single-cell, multiplex data, using toric systems theory. PLoS Comput. Biol. 2019; 15:e1007311. PubMed
  • Li Z, Pinch BJ, Olson CM, Donovan KA, Nowak RP, Mills CE, Scott DA, Doctor ZM, Eleuteri NA, Chung M, Sorger PK, Fischer ES, Gray NS. Development and Characterization of a Wee1 Kinase Degrader. Cell Chem Biol 2019. PubMed
  • Du Z, Lin JR, Rashid R, Maliga Z, Wang S, Aster JC, Izar B, Sorger PK, Santagata S. Qualifying antibodies for image-based immune profiling and multiplexed tissue imaging. Nat Protoc 2019; 14:2900-2930. PubMed
  • Krueger R, Beyer J, Jang WD, Kim NW, Sokolov A, Sorger PK, Pfister H. Facetto: Combining Unsupervised and Supervised Learning for Hierarchical Phenotype Analysis in Multi-Channel Image Data. IEEE Trans Vis Comput Graph 2019. PubMed
  • Niepel M, Hafner M, Mills CE, Subramanian K, Williams EH, Chung M, Gaudio B, Barrette AM, Stern AD, Hu B, Korkola JE, , Gray JW, Birtwistle MR, Heiser LM, Sorger PK. A Multi-center Study on the Reproducibility of Drug-Response Assays in Mammalian Cell Lines. Cell Syst 2019; 9:35-48.e5. PubMed
  • Rao S, Gurbani D, Du G, Everley RA, Browne CM, Chaikuad A, Tan L, Schröder M, Gondi S, Ficarro SB, Sim T, Kim ND, Berberich MJ, Knapp S, Marto JA, Westover KD, Sorger PK, Gray NS. Leveraging Compound Promiscuity to Identify Targetable Cysteines within the Kinome. Cell Chem Biol 2019; 26:818-829.e9. PubMed
  • Hafner M, Mills CE, Subramanian K, Chen C, Chung M, Boswell SA, Everley RA, Liu C, Walmsley CS, Juric D, Sorger PK. Multiomics Profiling Establishes the Polypharmacology of FDA-Approved CDK4/6 Inhibitors and the Potential for Differential Clinical Activity. Cell Chem Biol 2019. PubMed
  • Wang H, Sheehan RP, Palmer AC, Everley RA, Boswell SA, Ron-Harel N, Ringel AE, Holton KM, Jacobson CA, Erickson AR, Maliszewski L, Haigis MC, Sorger PK. Adaptation of Human iPSC-Derived Cardiomyocytes to Tyrosine Kinase Inhibitors Reduces Acute Cardiotoxicity via Metabolic Reprogramming. Cell Syst 2019; 8:412-426.e7. PubMed
  • Todorov PV, Gyori BM, Bachman JA, Sorger PK. INDRA-IPM: interactive pathway modeling using natural language with automated assembly. Bioinformatics 2019. PubMed
  • Moret N, Clark NA, Hafner M, Wang Y, Lounkine E, Medvedovic M, Wang J, Gray N, Jenkins J, Sorger PK. Cheminformatics Tools for Analyzing and Designing Optimized Small-Molecule Collections and Libraries. Cell Chem Biol 2019. PubMed
  • Ferguson FM, Doctor ZM, Ficarro SB, Browne CM, Marto JA, Johnson JL, Yaron TM, Cantley LC, Kim ND, Sim T, Berberich MJ, Kalocsay M, Sorger PK, Gray NS. Discovery of Covalent CDK14 Inhibitors with Pan-TAIRE Family Specificity. Cell Chem Biol 2019. PubMed
  • Rao S, Du G, Hafner M, Subramanian K, Sorger PK, Gray NS. A multi-targeted probe-based strategy to identify signaling vulnerabilities in cancers. J Biol Chem 2019. PubMed
  • Olson CM, Liang Y, Leggett A, Park WD, Li L, Mills CE, Elsarrag SZ, Ficarro SB, Zhang T, Düster R, Geyer M, Sim T, Marto JA, Sorger PK, Westover KD, Lin CY, Kwiatkowski N, Gray NS. Development of a Selective CDK7 Covalent Inhibitor Reveals Predominant Cell-Cycle Phenotype. Cell Chem Biol 2019. PubMed
  • Palmer AC, Chidley C, Sorger PK. A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity. Elife 2019. PubMed
  • Song Y, Subramanian K, Berberich MJ, Rodriguez S, Latorre IJ, Luria CM, Everley R, Albers MW, Mitchison TJ, Sorger PK. A dynamic view of the proteomic landscape during differentiation of ReNcell VM cells, an immortalized human neural progenitor line. Sci Data 2019; 6:190016. PubMed
  • Jerby-Arnon L, Shah P, Cuoco MS, Rodman C, Su MJ, Melms JC, Leeson R, Kanodia A, Mei S, Lin JR, Wang S, Rabasha B, Liu D, Zhang G, Margolais C, Ashenberg O, Ott PA, Buchbinder EI, Haq R, Hodi FS, Boland GM, Sullivan RJ, Frederick DT, Miao B, Moll T, Flaherty KT, Herlyn M, Jenkins RW, Thummalapalli R, Kowalczyk MS, Cañadas I, Schilling B, Cartwright ANR, Luoma AM, Malu S, Hwu P, Bernatchez C, Forget MA, Barbie DA, Shalek AK, Tirosh I, Sorger PK, Wucherpfennig K, Van Allen EM, Schadendorf D, Johnson BE, Rotem A, Rozenblatt-Rosen O, Garraway LA, Yoon CH, Izar B, Regev A. A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade. Cell 2018; 175:984-997.e24. PubMed
  • Lin JR, Izar B, Wang S, Yapp C, Mei S, Shah PM, Santagata S, Sorger PK. Highly multiplexed immunofluorescence imaging of human tissues and tumors using t-CyCIF and conventional optical microscopes. Elife 2018. PubMed
  • Bachman JA, Gyori BM, Sorger PK. FamPlex: a resource for entity recognition and relationship resolution of human protein families and complexes in biomedical text mining. BMC Bioinformatics 2018; 19:248. PubMed
  • Sampattavanich S, Steiert B, Kramer BA, Gyori BM, Albeck JG, Sorger PK. Encoding Growth Factor Identity in the Temporal Dynamics of FOXO3 under the Combinatorial Control of ERK and AKT Kinases. Cell Syst 2018; 6:664-678.e9. PubMed
  • Koch PD, Miller HR, Yu G, Tallarico JA, Sorger PK, Wang Y, Feng Y, Thomas JR, Ross NT, Mitchison T. A High Content Screen in Macrophages Identifies Small Molecule Modulators of STING-IRF3 and NFkB Signaling. ACS Chem Biol 2018. PubMed
  • Coy S, Rashid R, Lin JR, Du Z, Donson AM, Hankinson TC, Foreman NK, Manley PE, Kieran MW, Reardon DA, Sorger PK, Santagata S. Multiplexed Immunofluorescence Reveals Potential PD-1/PD-L1 Pathway Vulnerabilities in Craniopharyngioma. 2018. PubMed
  • Gonzalez Herrera KN, Zaganjor E, Ishikawa Y, Spinelli JB, Yoon H, Lin JR, Satterstrom FK, Ringel A, Mulei S, Souza A, Gorham JM, Benson CC, Seidman JG, Sorger PK, Clish CB, Haigis MC. Small-Molecule Screen Identifies De Novo Nucleotide Synthesis as a Vulnerability of Cells Lacking SIRT3. Cell Rep 2018; 22:1945-1955. PubMed
  • Dunn IF, Du Z, Touat M, Sisti MB, Wen PY, Umeton R, Dubuc AM, Ducar M, Canoll PD, Severson E, Elvin JA, Ramkissoon SH, Lin JR, Cabrera L, Acevedo B, Sorger PK, Ligon KL, Santagata S, Reardon DA. Mismatch repair deficiency in high-grade meningioma: a rare but recurrent event associated with dramatic immune activation and clinical response to PD-1 blockade. JCO Precis Oncol 2018. PubMed
  • Palmer AC, Sorger PK. Combination Cancer Therapy Can Confer Benefit via Patient-to-Patient Variability without Drug Additivity or Synergy. Cell 2017; 171:1678-1691.e13. PubMed
  • Keenan AB, Jenkins SL, Jagodnik KM, Koplev S, He E, Torre D, Wang Z, Dohlman AB, Silverstein MC, Lachmann A, Kuleshov MV, Ma'ayan A, Stathias V, Terryn R, Cooper D, Forlin M, Koleti A, Vidovic D, Chung C, Schürer SC, Vasiliauskas J, Pilarczyk M, Shamsaei B, Fazel M, Ren Y, Niu W, Clark NA, White S, Mahi N, Zhang L, Kouril M, Reichard JF, Sivaganesan S, Medvedovic M, Meller J, Koch RJ, Birtwistle MR, Iyengar R, Sobie EA, Azeloglu EU, Kaye J, Osterloh J, Haston K, Kalra J, Finkbiener S, Li J, Milani P, Adam M, Escalante-Chong R, Sachs K, Lenail A, Ramamoorthy D, Fraenkel E, Daigle G, Hussain U, Coye A, Rothstein J, Sareen D, Ornelas L, Banuelos M, Mandefro B, Ho R, Svendsen CN, Lim RG, Stocksdale J, Casale MS, Thompson TG, Wu J, Thompson LM, Dardov V, Venkatraman V, Matlock A, Van Eyk JE, Jaffe JD, Papanastasiou M, Subramanian A, Golub TR, Erickson SD, Fallahi-Sichani M, Hafner M, Gray NS, Lin JR, Mills CE, Muhlich JL, Niepel M, Shamu CE, Williams EH, Wrobel D, Sorger PK, Heiser LM, Gray JW, Korkola JE, Mills GB, LaBarge M, Feiler HS, Dane MA, Bucher E, Nederlof M, Sudar D, Gross S, Kilburn DF, Smith R, Devlin K, Margolis R, Derr L, Lee A, Pillai A. The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations. Cell Syst 2017. PubMed
  • Gyori BM, Bachman JA, Subramanian K, Muhlich JL, Galescu L, Sorger PK. From word models to executable models of signaling networks using automated assembly. Mol Syst Biol 2017; 13:954. PubMed
  • Niepel M, Hafner M, Duan Q, Wang Z, Paull EO, Chung M, Lu X, Stuart JM, Golub TR, Subramanian A, Ma'ayan A, Sorger PK. Common and cell-type specific responses to anti-cancer drugs revealed by high throughput transcript profiling. Nat Commun 2017; 8:1186. PubMed
  • Clark NA, Hafner M, Kouril M, Williams EH, Muhlich JL, Pilarczyk M, Niepel M, Sorger PK, Medvedovic M. GRcalculator: an online tool for calculating and mining dose-response data. BMC Cancer 2017; 17:698. PubMed
  • Werbin JL, Avendaño MS, Becker V, Jungmann R, Yin P, Danuser G, Sorger PK. Multiplexed Exchange-PAINT imaging reveals ligand-dependent EGFR and Met interactions in the plasma membrane. Sci Rep 2017; 7:12150. PubMed
  • Niepel M, Hafner M, Chung M, Sorger PK. Measuring Cancer Drug Sensitivity and Resistance in Cultured Cells. Curr Protoc Chem Biol 2017; 9:55-74. PubMed
  • Hafner M, Niepel M, Subramanian K, Sorger PK. Designing Drug-Response Experiments and Quantifying their Results. Curr Protoc Chem Biol 2017; 9:96-116. PubMed
  • Hafner M, Niepel M, Sorger PK. Alternative drug sensitivity metrics improve preclinical cancer pharmacogenomics. Nat Biotechnol 2017; 35:500-502. PubMed
  • Suderman R, Bachman JA, Smith A, Sorger PK, Deeds EJ. Fundamental trade-offs between information flow in single cells and cellular populations. Proc Natl Acad Sci U S A 2017; 114:5755-5760. PubMed
  • Foijer F, Albacker LA, Bakker B, Spierings DC, Yue Y, Xie SZ, Davis SH, Lutum-Jehle A, Takemoto D, Hare B, Furey B, Bronson RT, Lansdorp PM, Bradley A, Sorger PK. Deletion of the MAD2L1 spindle assembly checkpoint gene is tolerated in mouse models of acute T-cell lymphoma and hepatocellular carcinoma. Elife 2017. PubMed
  • Tan L, Gurbani D, Weisberg EL, Jones DS, Rao S, Singer WD, Bernard FM, Mowafy S, Jenney A, Du G, Nonami A, Griffin JD, Lauffenburger DA, Westover KD, Sorger PK, Gray NS. Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. Bioorg Med Chem 2017; 25:1320-1328. PubMed
  • Tan L, Gurbani D, Weisberg EL, Hunter JC, Li L, Jones DS, Ficarro SB, Mowafy S, Tam CP, Rao S, Du G, Griffin JD, Sorger PK, Marto JA, Westover KD, Gray NS. Structure-guided development of covalent TAK1 inhibitors. Bioorg Med Chem 2017; 25:838-846. PubMed
  • Fallahi-Sichani M, Becker V, Izar B, Baker GJ, Lin JR, Boswell SA, Shah P, Rotem A, Garraway LA, Sorger PK. Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de-differentiated state. Mol Syst Biol 2017; 13:905. PubMed
  • Jones DS, Jenney AP, Swantek JL, Burke JM, Lauffenburger DA, Sorger PK. Profiling drugs for rheumatoid arthritis that inhibit synovial fibroblast activation. Nat Chem Biol 2017; 13:38-45. PubMed
  • Hafner M, Heiser LM, Williams EH, Niepel M, Wang NJ, Korkola JE, Gray JW, Sorger PK. Quantification of sensitivity and resistance of breast cancer cell lines to anti-cancer drugs using GR metrics. Sci Data 2017; 4:170166. PubMed
  • Lin JR, Fallahi-Sichani M, Chen JY, Sorger PK. Cyclic Immunofluorescence (CycIF), A Highly Multiplexed Method for Single-cell Imaging. Curr Protoc Chem Biol 2016; 8:251-264. PubMed
  • Hafner M, Niepel M, Chung M, Sorger PK. Growth rate inhibition metrics correct for confounders in measuring sensitivity to cancer drugs. Nat Methods 2016; 13:521-7. PubMed
  • AlQuraishi M, Sorger PK. Reproducibility will only come with data liberation. Sci Transl Med 2016; 8:339ed7. PubMed
  • Tirosh I, Izar B, Prakadan SM, Wadsworth MH, Treacy D, Trombetta JJ, Rotem A, Rodman C, Lian C, Murphy G, Fallahi-Sichani M, Dutton-Regester K, Lin JR, Cohen O, Shah P, Lu D, Genshaft AS, Hughes TK, Ziegler CG, Kazer SW, Gaillard A, Kolb KE, Villani AC, Johannessen CM, Andreev AY, Van Allen EM, Bertagnolli M, Sorger PK, Sullivan RJ, Flaherty KT, Frederick DT, Jané-Valbuena J, Yoon CH, Rozenblatt-Rosen O, Shalek AK, Regev A, Garraway LA. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 2016; 352:189-196. PubMed
  • Shi T, Niepel M, McDermott JE, Gao Y, Nicora CD, Chrisler WB, Markillie LM, Petyuk VA, Smith RD, Rodland KD, Sorger PK, Qian WJ, Wiley HS. Conservation of protein abundance patterns reveals the regulatory architecture of the EGFR-MAPK pathway. Sci Signal 2016; 9:rs6. PubMed
  • Flusberg DA, Sorger PK. Surviving apoptosis: life-death signaling in single cells. Trends Cell Biol 2015. PubMed
  • Roux J, Hafner M, Bandara S, Sims JJ, Hudson H, Chai D, Sorger PK. Fractional killing arises from cell-to-cell variability in overcoming a caspase activity threshold. Mol Syst Biol 2015; 11:803. PubMed
  • Fallahi-Sichani M, Moerke NJ, Niepel M, Zhang T, Gray NS, Sorger PK. Systematic analysis of BRAF(V600E) melanomas reveals a role for JNK/c-Jun pathway in adaptive resistance to drug-induced apoptosis. Mol Syst Biol 2015; 11:797. PubMed
  • Lin JR, Fallahi-Sichani M, Sorger PK. Highly multiplexed imaging of single cells using a high-throughput cyclic immunofluorescence method. Nat Commun 2015; 6:8390. PubMed
  • AlQuraishi M, Koytiger G, Jenney A, MacBeath G, Sorger PK. A multiscale statistical mechanical framework integrates biophysical and genomic data to assemble cancer networks. Nat Genet 2014; 46:1363-71. PubMed
  • Gujral TS, Chan M, Peshkin L, Sorger PK, Kirschner MW, MacBeath G. A noncanonical Frizzled2 pathway regulates epithelial-mesenchymal transition and metastasis. Cell 2014; 159:844-56. PubMed
  • Foijer F, Xie SZ, Simon JE, Bakker PL, Conte N, Davis SH, Kregel E, Jonkers J, Bradley A, Sorger PK. Chromosome instability induced by Mps1 and p53 mutation generates aggressive lymphomas exhibiting aneuploidy-induced stress. Proc Natl Acad Sci U S A 2014; 111:13427-32. PubMed
  • Duan Q, Flynn C, Niepel M, Hafner M, Muhlich JL, Fernandez NF, Rouillard AD, Tan CM, Chen EY, Golub TR, Sorger PK, Subramanian A, Ma'ayan A. LINCS Canvas Browser: interactive web app to query, browse and interrogate LINCS L1000 gene expression signatures. Nucleic Acids Res 2014. PubMed
  • Kallenberger SM, Beaudouin J, Claus J, Fischer C, Sorger PK, Legewie S, Eils R. Intra- and interdimeric caspase-8 self-cleavage controls strength and timing of CD95-induced apoptosis. Sci Signal 2014; 7:ra23. PubMed
  • Niepel M, Hafner M, Pace EA, Chung M, Chai DH, Zhou L, Muhlich JL, Schoeberl B, Sorger PK. Analysis of growth factor signaling in genetically diverse breast cancer lines. BMC Biol 2014; 12:20. PubMed
  • Paull EO, Carlin DE, Niepel M, Sorger PK, Haussler D, Stuart JM. Discovering causal pathways linking genomic events to transcriptional states using Tied Diffusion Through Interacting Events (TieDIE). Bioinformatics 2013; 29:2757-64. PubMed
  • Fallahi-Sichani M, Honarnejad S, Heiser LM, Gray JW, Sorger PK. Metrics other than potency reveal systematic variation in responses to cancer drugs. Nat Chem Biol 2013; 9:708-14. PubMed
  • Niepel M, Hafner M, Pace EA, Chung M, Chai DH, Zhou L, Schoeberl B, Sorger PK. Profiles of Basal and stimulated receptor signaling networks predict drug response in breast cancer lines. Sci Signal 2013; 6:ra84. PubMed
  • Marco E, Dorn JF, Hsu PH, Jaqaman K, Sorger PK, Danuser G. S. cerevisiae chromosomes biorient via gradual resolution of syntely between S phase and anaphase. Cell 2013; 154:1127-39. PubMed
  • Flusberg DA, Roux J, Spencer SL, Sorger PK. Cells surviving fractional killing by TRAIL exhibit transient but sustainable resistance and inflammatory phenotypes. Mol Biol Cell 2013; 24:2186-200. PubMed
  • Flusberg DA, Sorger PK. Modulating cell-to-cell variability and sensitivity to death ligands by co-drugging. Phys Biol 2013; 10:035002. PubMed
  • Koch Y, Wolf T, Sorger PK, Eils R, Brors B. Decision-tree based model analysis for efficient identification of parameter relations leading to different signaling states. PLoS ONE 2013; 8:e82593. PubMed
  • Thurber GM, Yang KS, Reiner T, Kohler RH, Sorger P, Mitchison T, Weissleder R. Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo. Nat Commun 2013; 4:1504. PubMed
  • Sorger PK, Schoeberl B. An expanding role for cell biologists in drug discovery and pharmacology. Mol Biol Cell 2012; 23:4162-4. PubMed
  • Luckert K, Götschel F, Sorger PK, Hecht A, Joos TO, Pötz O. Snapshots of protein dynamics and post-translational modifications in one experiment--beta-catenin and its functions. Mol Cell Proteomics 2011. PubMed
  • Spencer SL, Sorger PK. Measuring and modeling apoptosis in single cells. Cell 2011; 144:926-39. PubMed
  • Morris MK, Saez-Rodriguez J, Clarke DC, Sorger PK, Lauffenburger DA. Training signaling pathway maps to biochemical data with constrained fuzzy logic: quantitative analysis of liver cell responses to inflammatory stimuli. PLoS Comput. Biol. 2011; 7:e1001099. PubMed
  • Espelin CW, Goldsipe A, Sorger PK, Lauffenburger DA, de Graaf D, Hendriks BS. Elevated GM-CSF and IL-1beta levels compromise the ability of p38 MAPK inhibitors to modulate TNFalpha levels in the human monocytic/macrophage U937 cell line. Mol Biosyst 2010; 6:1956-72. PubMed
  • Alexopoulos LG, Saez Rodriguez J, Cosgrove BD, Lauffenburger DA, Sorger PK. Networks inferred from biochemical data reveal profound differences in TLR and inflammatory signaling between normal and transformed hepatocytes. Mol Cell Proteomics 2010; 9:1849-65. PubMed
  • Chen WW, Niepel M, Sorger PK. Classic and contemporary approaches to modeling biochemical reactions. Genes Dev 2010; 24:1861-75. PubMed
  • Cosgrove BD, Alexopoulos LG, Hang TC, Hendriks BS, Sorger PK, Griffith LG, Lauffenburger DA. Cytokine-associated drug toxicity in human hepatocytes is associated with signaling network dysregulation. Mol Biosyst 2010; 6:1195-206. PubMed
  • Lazzara MJ, Lane K, Chan R, Jasper PJ, Yaffe MB, Sorger PK, Jacks T, Neel BG, Lauffenburger DA. Impaired SHP2-mediated extracellular signal-regulated kinase activation contributes to gefitinib sensitivity of lung cancer cells with epidermal growth factor receptor-activating mutations. Cancer Res 2010; 70:3843-50. PubMed
  • Morris MK, Saez-Rodriguez J, Sorger PK, Lauffenburger DA. Logic-based models for the analysis of cell signaling networks. Biochemistry 2010; 49:3216-24. PubMed
  • Prill RJ, Marbach D, Saez-Rodriguez J, Sorger PK, Alexopoulos LG, Xue X, Clarke ND, Altan-Bonnet G, Stolovitzky G. Towards a rigorous assessment of systems biology models: the DREAM3 challenges. PLoS ONE 2010; 5:e9202. PubMed
  • Kim KA, Spencer SL, Albeck JG, Burke JM, Sorger PK, Gaudet S, Kim do H. Systematic calibration of a cell signaling network model. BMC Bioinformatics 2010; 11:202. PubMed
  • Spencer SL, Gaudet S, Albeck JG, Burke JM, Sorger PK. Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis. Nature 2009; 459:428-32. PubMed
  • Chen WW, Schoeberl B, Jasper PJ, Niepel M, Nielsen UB, Lauffenburger DA, Sorger PK. Input-output behavior of ErbB signaling pathways as revealed by a mass action model trained against dynamic data. Mol Syst Biol 2009; 5:239. PubMed
  • Saez-Rodriguez J, Alexopoulos LG, Epperlein J, Samaga R, Lauffenburger DA, Klamt S, Sorger PK. Discrete logic modelling as a means to link protein signalling networks with functional analysis of mammalian signal transduction. Mol Syst Biol 2009; 5:331. PubMed
  • Albeck JG, Burke JM, Spencer SL, Lauffenburger DA, Sorger PK. Modeling a snap-action, variable-delay switch controlling extrinsic cell death. PLoS Biol. 2008; 6:2831-52. PubMed
  • Albeck JG, Burke JM, Aldridge BB, Zhang M, Lauffenburger DA, Sorger PK. Quantitative analysis of pathways controlling extrinsic apoptosis in single cells. Mol Cell 2008; 30:11-25. PubMed
  • Janes KA, Gaudet S, Albeck JG, Nielsen UB, Lauffenburger DA, Sorger PK. The response of human epithelial cells to TNF involves an inducible autocrine cascade. Cell 2006; 124:1225-39. PubMed
  • Meraldi P, Draviam VM, Sorger PK. Timing and checkpoints in the regulation of mitotic progression. Dev Cell 2004; 7:45-60. PubMed
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