Pearson Lab Overcoming the complexity of cancer
Publications
Featured Article:
We found that cancers can be functionally stratified into just two types based on the activity of a single transcriptional complex. In “YAP ” cancers, the transcriptional co-activators, YAP and TAZ, drive oncogenesis via TEAD transcription factors. In contrast, we identified a broad group of “YAP ” cancers where YAP/TAZ-TEAD are instead tumor suppressors. These consist of many aggressive blood, neural and neuroendocrine cancers, such as small cell lung cancer (SCLC) and drug-resistant neuroendocrine prostate cancer. Mechanistically, YAP/TAZ-TEAD engage distinct enhancers and regulate unique transcriptional targets in YAP and YAP cancers, which drives opposite pro- vs. anti-cancer activities. Importantly, YAP and YAP cancers exhibit distinct therapeutic vulnerabilities, and lineage plasticity allows cancers to switch classes to evade therapeutics.
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2023
Aubry A, Pearson JD, Charish J, Yu T, Sivak JM, Xirodimas DP, Avet-Loiseau H, Corre J, Monnier PP, Bremner R. (2023) Deneddylation of Ribosomal Proteins Promotes Synergy between MLN4924 and Chemotherapy to Elicit Complete Therapeutic Responses. Cell Reports. 42, 112925.
2022
Knudsen ES, Kumarasamy V, Nambiar R, Pearson JD, Vail P, Rosenheck H, Wang J, Eng K, Bremner R, Schramek D, Rubin SM, Welm AL, Witkiewicz AK. CDK/cyclin dependencies define extreme cancer cell-cycle heterogeneity and collateral vulnerabilities. (2022) Cell Reports. 38, 110448.
Majeed S, Aparnathi MK, Nixon KCJ, Venkatasubramanian V, Rahman F, Song L, Weiss J, Barayan K, Sugumar V, Barghout SH, Pearson JD, Bremner R, Schimmer A, Tsao M, Liu G, Lok BH. Targeting the ubiquitin-proteasome system using the UBA1 inhibitor TAK-243 is a potential therapeutic strategy for small cell lung cancer. (2022) Clinical Cancer Research. 28:1966-1978.
Lu S, Duplat D, Benitez-Bolivar P, León C, Villota SD, Veloz-Villavicencio E, Arévalo V, Jaenes K, Guo Y, Cicek S, Robinson L, Peidis P, Pearson JD, Woodgett J, Mazzulli T, Ponce P, Restrepo S, González JM, Bernal A, Guevara-Suarez M, Pardee K, Cevallos VE, González C, Bremner R. Multicenter International Assessment of a SARS-CoV-2 RT-LAMP Test for Point of Care Clinical Application. (2022) PLoS One. 17(5):e0268340.
Pires L, Wilson BC, Bremner R, Lang A, Larouche J, McDonald R, Pearson JD, Trcka D, Wrana JL, Wu J, Whyne C. Translational feasibility and efficacy of nasal photodynamic disinfection of SARS-CoV-2. (2022) Scientific Reports. 12(1):14438.
Fan Y, Chen W, Qiang W, Wei R, Chen Y, Xiao L, Lin Y, Pearson JD, Yu T, Bremner R, Chen D. Mapping transgene insertion sites reveals α-Cre transgene expression in both developing retina and olfactory neurons. (2022) Communications Biology. 5, 411.
2021
Pearson JD, Huang K, Pacal M, McCurdy S, Lu S, Aubry A, Yu T, Wadosky KM, Zhang L, Wang T, Gregorieff A, Ahmad M, Dimaras H, Langille E, Cole SPC, Monnier P, Lok BH, Tsao M-S, Akeno N, Schramek D, Wikenheiser-Brokamp KA, Knudsen ES, Witkiewicz AK, Wrana J, Goodrich DW, Bremner R. (2021) Binary pan-cancer classes with distinct vulnerabilities defined by pro- or anti-cancer YAP/TEAD activity. Cancer Cell. 39:1115-1134.
- recomended in Faculty Opinions
Pearson JD, Bremner R. (2021) Lentiviral-mediated ectopic expression of YAP and TAZ in YAPoff cancer cell lines. STAR Protocols. 2, 100870.
Pearson JD, Bremner R. (2021) Simplifying Cancer: Binary Pan-Cancer Superclasses Stratified by Opposite YAP/TEAD Effects. Molecular & Cellular Oncology. 8, 1981111. [Commentary]
Pearson JD, Trcka D, Lu S, Hyduk SJ, Jen M, Aynaud M-M, Hernández JJ, Peidis P, Barrios-Rodiles M, Chan K, Woodgett J, Mazzulli T, Attisano L, Pelletier L, Cybulsky MI, Wrana JL, Bremner R. (2021) Comparison of SARS-CoV-2 Indirect and Direct RT-qPCR Detection Methods. Virology Journal. 18, 99.
Aynaud M-M, Hernandez JJ, Barutcu S, Braunschweig U, Chan K, Pearson JD, Trcka D, Prosser SL, Kim J, Barrios-Rodiles M, Jen M, Song S, Shen J, Bruce C, Hazlett B, Poutanen S, Attisano L, Bremner R, Blencowe BJ, Mazzulli T, Han H, Pelletier L, Wrana JL. (2021) A multiplexed, next generation sequencing platform for high-throughput detection of SARS-CoV-2. Nature Communications. 12, 1405.
Amalfitano E, Karlikow M, Norouzi M, Jaenes K, Cicek S, Masum F, Mousavi PS, Guo Y, Tang L, Sydor A, Ma D, Pearson JD, Trcka D, Pinette M, Ambagala A, Babiuk S, Pickering B, Wrana J, Bremner R, Mazzulli T, Sinton D, Brumell JH, Green AA, Pardee K. (2021) A Glucose Meter Interface for Point-of-Care Gene Circuit-based Diagnostics. Nature Communications. 12, 724.
Gurdita A, Nickerson PEB, Pokrajac NT, Ortín-Martínez A, Samuel Tsai EL, Comanita L, Yan NE, Dolati P, Tachibana N, Liu ZC, Pearson JD, Chen D, Bremner R, Wallace VA. (2021) InVision: An optimized tissue clearing approach for three-dimensional imaging and analysis of intact rodent eyes. iScience. 24:102905.
2020
Tsatskis Y*, Rosenfeld R*, Pearson JD*, Boswell C*, Qu Y, Kim K, Fabian L, Mohammad A, Wang X, Robson MI, Krchma K, Wu J, Gonçalves J, Hodzic D, Wu S, Potter D, Pelletier L, Dunham WH, Gingras AC, Sun Y, Meng J, Godt D, Schedl T, Ciruna B, Choi K, Perry J, Bremner R, Schirmer EC, Brill JA, Jurisicova A, McNeill H. (2020) The NEMP family supports metazoan fertility and nuclear envelope stiffness. Science Advances. 6: eabb4591.
* co-first authors
Aubry A, Pearson JD, Huang K, Livne-Bar I, Ahmad M, Jagadeesan M, Khetan V, Ketela T, Brown KR, Yu T, Lu S, Wrana JL, Moffat J, Bremner R. (2020) Functional genomics identifies new synergistic therapies for retinoblastoma. Oncogene. 39: 5338-57.
Lu Y, Shiau F, Yi W, Lu S, Wu Q, Pearson JD, Kallman A, Zhong S, Hoang T, Zuo Z, Zhao F, Zhang M, Tsai N, Zhuo Y, He S, Zhang J, Stein-O’Brien GL, Sherman TD, Duan X, Fertig EJ, Goff LA, Zack DJ, Handa JT, Xue T, Bremner R, Blackshaw S, Wang X, Clark BS. (2020) Single-Cell Analysis of Human Retina Identifies Evolutionarily Conserved and Species-Specific Mechanisms Controlling Development. Developmental Cell. 53: 473-91.