Wan Lab members in bold
*co-first; #co-corresponding
2024
Song L*, Li Q*, Xia L, Sahay A, Qiu Q, Li Y, Li H, Sasaki K, Susztak K, Wu H, Wan L. Single-Cell multiomics reveals ENL mutation perturbs kidney developmental trajectory by rewiring gene regulatory landscape. BioRxiv doi: https://doi.org/10.1101/2024.05.09.591709
Mathias KM*, Liu Y*, Wan L. Dysregulation of transcriptional condensates in human disease: mechanisms, biological functions, and open questions. Current Opinion in Genetics & Development 2024 Jun:86:102203. doi: 10.1016/j.gde.2024.102203. Epub 2024 May 23. PMID: 38788489
Liu Y*, Li Q*, Song L, Gong C, Tang S, Budinich KA, Vanderbeck A, Mathias KM, Wertheim GB, Nguyen SC, Outen R, Joyce EF, Maillard I, Wan L. Condensate-promoting ENL mutation drives tumorigenesis in vivo through dynamic regulation of histone modifications and gene expression. Cancer Discovery. 2024 Apr 24. doi: 10.1158/2159-8290.CD-23-0876. Online ahead of print. PMID: 38655899
Michino M*, Khan TA*, Miller MW, Fukase Y, Vendome J, Adura C, Glickman JF, Liu Y, Wan L, Allis CD, Stamford AW, Meinke PT, Renzetti LM, Kargman S, Liverton NJ, Huggins DJ. Lead Optimization of Small Molecule ENL YEATS Inhibitors to Enable In Vivo Studies: Discovery of TDI-11055. ACS Med. Chem. Lett. 2024,15, 4, 524–532, PMID: 38628784
2023
Acosta J, Li Q, Freeburg N, Murali N, Indeglia A, Grothusen G, Cicchini M, Mai H, Gladstein A, Adler K, Doerig K, Li J, Ruiz-Torres M, Manning K, Stanger B, Busino L, Murphy M, Wan L, Feldser D. p53 restoration in small cell lung cancer identifies a latent Cyclophilin-dependent necrosis mechanism. Nature Communications 2023 Jul 21;14(1):4403. doi: 10.1038/s41467-023-40161-9. PMID: 37479684; PMCID: PMC10362054
Zhou N, Choi J, Grothusen G, Kim BJ , Ren D, Cao Z, Beer T, Tang HY, Perkey E, Maillard I, Bonasio R, Shi J, Liu Y, Li Q, Inamdar A, Ruella M, Wan L, Busino L. DLBCL associated NOTCH2 mutations escape ubiquitin-dependent degradation and promote chemo-resistance. Blood 2023 Sep 14;142(11):973-988. PMID: 37235754. doi: 10.1182/blood.2022018752.
Wang X*, Fan D*, Han Q*, Liu Y*, Miao H, Wang X, Li Q, Chen D, Gore H, Himadewi P, Pfeifer GP, Cierpicki T, Grembecka J, Su J, Chong S#, Wan L#, Zhang X#. Mutant NPM1 hijacks transcriptional hub to maintain pathogenic gene programs in acute myeloid leukemia. Cancer Discovery. 2023 Mar 1;13(3):724-745. PMC9975662 (*co-first; #co-corresponding)
Chi P, Lewis PW, Lu C#, Lu J, Ruthenburg AJ, Sabari BR, Shechter D, Wan L, Wang GG#. Charles David Allis (1951–2023). Nature Genetics 2023 volume 55, pages 522–523. PMID: 36849658
2022
Liu Y, Li H, Alikarami F, Barrett DR, Khan TA, Michino M, Hill C, Mahdavi L, Song L, Tang S, Yang L, Li Y, Pokharel SP, Li Q, Stamford AW, Liverton N, Renzetti LM, Taylor S, Watt GF, Ladduwahetty T, Kargman S, Meinke PT, Foley MA, Shi J, Li H, Chen CW, Gardini A, Huggins DJ, Bernt KM#, Wan L#. Small-molecule inhibition of the acyl-lysine reader ENL as a strategy against acute myeloid leukemia. Cancer Discovery. 2022 Nov 2;12(11):2684-2709. PMID: 36053276 (#co-corresponding)
Song L*, Yao X*, Li H, Peng B, Boka AP, Liu Y, Chen G, Liu Z, Mathias KM, Xia L, Li Q, Mir M, Li Y#, Li H#, Wan L#. Hotspot mutations in the structured ENL YEATS domain link aberrant transcriptional condensates and cancer. Molecular Cell, 2022 Nov 3;82(21):4080-4098.e12. PMID:36272410 (*co-first;#co-corresponding)
Yan F, Li J, Milosevic J, Petroni R, Liu S, Shi Z, Yuan S, Reynaga JM, Qi Y, Rico J, Yu S, Liu Y, Rokudai S, Palmisiano N, Meyer SE, Sung PJ, Wan L, Lan F, Garcia BA, Stanger BZ, Sykes DB, Blanco MA. KAT6A and ENL form an epigenetic transcriptional control module to drive critical leukemogenic gene expression programs. Cancer Discovery 2022 Mar 1;12(3):792-811. PMID: 34853079.
Shen M, Wei Y, Kim H, Wan L, Jiang, Y, Hang X, Raba M, Remiszewski S, Rowicki M, Wu C, Wu S, Zhang L, Lu X, Yuan M, Smith AS, Zheng A, Bertino J, Jin JF, Xing Y, Shao Z, Kang Y. Small-molecule inhibitors that disrupt the MTDH–SND1 complex suppress breast cancer progression and metastasis. Nature Cancer, 2022 Jan;3(1):43-59. PMID: 35121987
Shen, M., Smith, H.A., Wei, Y., Jiang Y., Zhao S., Wang N., Rowicki M., Tang Y., Hang X., Wu S., Wan L., Shao Z., Kang Y. Pharmacological disruption of the MTDH–SND1 complex enhances tumor antigen presentation and synergizes with anti-PD-1 therapy in metastatic breast cancer. Nature Cancer 2022 Jan;3(1):60-74. PMID: 35121988
2021
Akkari L, Finley SD, Ho P, Jenkins M, Maier BB, McGranahan N, Mutebi M, Perera RM, Robles-Espinoza CD, Vardhana S, Wan L, Xu M. Challenges and opportunities in 2021. Nature Cancer volume 2, pages1278–1283 (2021)
Shen M, Xie S, Rowicki M, Michel S, Wei Y, Hang X, Wan L, Lu X, Yuan M, Jin JF, Jaschinski F, Zhou T, Klar R, Kang Y. Therapeutic Targeting of Metadherin Suppresses Colorectal and Lung Cancer Progression and Metastasis. Cancer Research. 2020 Nov 25; doi: 10.1158/0008-5472.CAN-20-1876.
Liling’ postdoc work
2020
Wan L#, Chong S, Fan X, Liang A, Cui X, Gates L, Carroll TS, Li Y, Feng L, Chen G, Wang S, Ortiz MV, Daley S, Wang X, Xuan H, Kentsis A, Muir TW, Roeder RG, Li H, Li W, Tjian R, Wen H#, Allis CD#. Impaired Cell Fate through Gain-of-function Mutations in a Chromatin Reader. Nature. 2020 Jan; 577(7788):121-126 (#co-corresponding)
Featured in Cancer Discovery Rockefeller News F1000Prime
In this study, we and our collaborators demonstrate, for the first time, that recurrent, hotspot mutations in a chromatin reader domain drive self-reinforced recruitment, which in turn, derail normal cell fate control during development leading to an oncogenic outcome.
2018
Li X, Li XM, Jiang Y, Liu Z, Cui Y, Fung KY, van der Beelen SHE, Tian G, Wan L, Shi X, Allis CD, Li H, Li Y, Li XD. Structure-guided development of YEATS domain inhibitors by targeting π-π-π stacking. Nat Chem Biol. 2018 Dec;14(12):1140-1149. PMC6503841
2017
Wan L*, Wen H*, Li Y*, Lyu J, Xi Y, Hoshii T, Joseph JK, Wang X, Loh YE, Erb MA, Souza AL, Bradner JE, Shen L, Li W, Li H, Allis CD#, Armstrong SA#, Shi X#. ENL links histone acetylation to oncogenic gene expression in acute myeloid leukaemia. Nature 2017 Mar 9;543(7644):265-269. (*Equal contribution, ). PMC5372383
Featured in Nature News, Nature Reviews Cancer, Nature Reviews Clinical Oncology, Cancer Discovery and Rockefeller News
In this collaborative study, we identified a novel ‘reader’ for histone acetylation named ENL and elucidated how its reading of histone acetylation plays a key role in sustaining the leukemia stem state. This study provides the first evidence to support a role of the well-conserved YEATS domain in human cancer and motivates ongoing efforts to develop YEATS domain inhibitors as novel cancer therapies.
2016
Li Y*, Sabari BR*, Panchenko T*, Wen H, Zhao D, Guan H, Wan L, Huang H, Tang Z, Zhao Y, Roeder RG, Shi X, Allis CD, Li H. (2016) Molecular Coupling of Histone Crotonylation and Active Transcription by AF9 YEATS Domain. Molecular Cell 2016 Apr 21;62(2):181-93. PMC4841940
Liling’s graduate work
2014
Wan L, Lu X, Yuan S, Wei Y, Guo F, Shen M, Yuan M, Chakrabarti R, Hua Y, Smith HA, Blanco MA, Chekmareva M, Wu H, Bronson RT, Haffty BG, Xing Y, Kang Y. MTDH-SND1 interaction is crucial for expansion and activity of tumor-initiating cells in diverse oncogene- and carcinogen-induced mammary tumors. Cancer Cell 2014 Jul 14;26(1):92-105. PMC4101059
Featured in Cell Stem Cell, Cancer Discovery and Science Daily
Guo F*, Wan L*, Zheng A, Stanevich V, Wei Y, Satyshur KA, Shen M, Lee W, Kang Y, Xing Y. Structural insights into the tumor-promoting function of the MTDH-SND1 complex. Cell Reports 2014 Sep 25;8(6):1704-13. (*Equal contribution). PMC4309369
Wan L, Hu G, Wei Y, Yuan M, Bronson RT, Yang Q, Siddiqui J, Pienta KJ, Kang Y. Genetic ablation of metadherin inhibits autochthonous prostate cancer progression and metastasis. Cancer Research 2014 Sep 15;74(18):5336-47. PMC4167565
2013
Wan L, Pantel K, Kang Y. Tumor metastasis: moving new biological insights into the clinic. Nature Medicine 2013 Nov;19(11):1450-64. PMID: 24202397
Wan L, Kang Y. (2013) Pleiotropic roles of AEG-1/MTDH/LYRIC in breast cancer. Advances in Cancer Research. 2013;120:113-34. PMID: 23889989
Alexia C, Poalas K, Carvalho G, Zemirli N, Dwyer J, Dubois SM, Hatchi EM, Cordeiro N, Smith SS, Castanier C, Le Guelte A, Wan L, Kang Y, Vazquez A, Gavard J, Arnoult D, Bidère N. The endoplasmic reticulum acts as a platform for ubiquitylated components of nuclear factor κB signaling. Science Signaling 2013 Sep 3;6(291):ra79. PMID: 24003256