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P53 LABORATORY

 

Welcome to the p53Lab

 
ImageThe p53 lab is focusing on the development of new therapies, new diagnostics and new discoveries in the p53 pathway. 11 Million people living with cancer have specific mutations in the p53 gene leading to the production of a faulty p53 protein. This is half the cases of human cancer. In those that have an apparently normal p53 gene we believe that there are faults in the p53 pathway. We are using a variety of approaches to translate this extraordinary finding into clinical benefit. We work closely with many other groups both in Singapore and in the rest of the world to achieve this. We are using biochemical, biophysical, cell biological and genetic approaches in our work and offer an outstanding international training environment

News

2020

2019


Upcoming Conferences

2021

2022

Current Publications


Conformational ordering of intrinsically disordered peptides for targeting translation initiation. Brown CJ, Verma CS, Lane DP, Lama D. Biochim Biophys Acta Gen Subj. 2021 Jan;1865(1):129775. doi: 10.1016/j.bbagen.2020.129775.

Exploitation of dihydroorotate dehydrogenase (DHODH) and p53 activation as therapeutic targets: A case study in polypharmacology. Ladds MJGW, Popova G, Pastor-Fernández A, Kannan S, van Leeuwen IMM, Håkansson M, Walse B, Tholander F, Bhatia R, Verma CS, Lane DP, Laín S. J Biol Chem. 2020 Dec 25;295(52):17935-17949. doi: 10.1074/jbc.RA119.012056.

Directed co-evolution of interacting protein-peptide pairs by compartmentalized two-hybrid replication (C2HR). Siau JW, Nonis S, Chee S, Koh LQ, Ferrer FJ, Brown CJ, Ghadessy FJ. Nucleic Acids Res. 2020 Dec 16;48(22):e128. doi: 10.1093/nar/gkaa933.

The Novel Anti-cMet Antibody seeMet 12 Potentiates Sorafenib Therapy and Radiotherapy in a Colorectal Cancer Model. Spiegelberg D, Mortensen ACL, Palupi KD, Micke P, Wong J, Vojtesek B, Lane DP, Nestor M. Front Oncol. 2020 Sep 11;10:1717. doi: 10.3389/fonc.2020.01717.

A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma. Johansson P, Krona C, Kundu S, Doroszko M, Baskaran S, Schmidt L, Vinel C, Almstedt E, Elgendy R, Elfineh L, Gallant C, Lundsten S, Ferrer Gago FJ, Hakkarainen A, Sipilä P, Häggblad M, Martens U, Lundgren B, Frigault MM, Lane DP, Swartling FJ, Uhrbom L, Nestor M, Marino S, Nelander S. Cell Rep. 2020 Jul 14;32(2):107897. doi: 10.1016/j.celrep.2020.107897.

High intracellular stability of the spidroin N-terminal domain in spite of abundant amyloidogenic segments revealed by in-cell hydrogen/deuterium exchange mass spectrometry. Kaldmäe M, Leppert A, Chen G, Sarr M, Sahin C, Nordling K, Kronqvist N, Gonzalvo-Ulla M, Fritz N, Abelein A, Laίn S, Biverstål H, Jörnvall H, Lane DP, Rising A, Johansson J, Landreh M. FEBS J. 2020 Jul;287(13):2823-2833. doi: 10.1111/febs.15169.

Combining native and 'omics' mass spectrometry to identify endogenous ligands bound to membrane proteins. Gault J, Liko I, Landreh M, Shutin D, Bolla JR, Jefferies D, Agasid M, Yen HY, Ladds MJGW, Lane DP, Khalid S, Mullen C, Remes PM, Huguet R, McAlister G, Goodwin M, Viner R, Syka JEP, Robinson CV. Nat Methods. 2020 May;17(5):505-508. doi: 10.1038/s41592-020-0821-0.

Macrocyclization of an all-d linear α-helical peptide imparts cellular permeability. Kannan S, Aronica PGA, Ng S, Gek Lian DT, Frosi Y, Chee S, Shimin J, Yuen TY, Sadruddin A, Kaan HYK, Chandramohan A, Wong JH, Tan YS, Chang ZW, Ferrer-Gago FJ, Arumugam P, Han Y, Chen S, Rénia L, Brown CJ, Johannes CW, Henry B, Lane DP, Sawyer TK, Verma CS, Partridge AW. Chem Sci. 2020 May 11;11(21):5577-5591. doi: 10.1039/c9sc06383h.

De-risking Drug Discovery of Intracellular Targeting Peptides: Screening Strategies to Eliminate False-Positive Hits. Ng S, Juang YC, Chandramohan A, Kaan HYK, Sadruddin A, Yuen TY, Ferrer-Gago FJ, Lee XC, Liew X, Johannes CW, Brown CJ, Kannan S, Aronica PG, Berglund NA, Verma CS, Liu L, Stoeck A, Sawyer TK, Partridge AW, Lane DP. ACS Med Chem Lett. 2020 May 1;11(10):1993-2001. doi: 10.1021/acsmedchemlett.0c00022.

Targeting codon 158 p53-mutant cancers via the induction of p53 acetylation.Kong LR, Ong RW, Tan TZ, Mohamed Salleh NAB, Thangavelu M, Chan JV, Koh LYJ, Periyasamy G, Lau JA, Le TBU, Wang L, Lee M, Kannan S, Verma CS, Lim CM, Chng WJ, Lane DP, Venkitaraman A, Hung HT, Cheok CF, Goh BC. Nat Commun. 2020 Apr 29;11(1):2086. doi: 10.1038/s41467-020-15608-y.

Optimization of Tetrahydroindazoles as Inhibitors of Human Dihydroorotate Dehydrogenase and Evaluation of Their Activity and In Vitro Metabolic Stability..Popova G, Ladds MJGW, Johansson L, Saleh A, Larsson J, Sandberg L, Sahlberg SH, Qian W, Gullberg H, Garg N, Gustavsson AL, Haraldsson M, Lane D, Yngve U, Lain S. J Med Chem. 2020 Apr 23;63(8):3915-3934. doi: 0.1021/acs.jmedchem.9b01658.

Combined proinflammatory cytokine and cognate activation of invariant natural killer T cells enhances anti-DNA antibody responses. Sedimbi SK, Hägglöf T, Garimella MG, Wang S, Duhlin A, Coelho A, Ingelshed K, Mondoc E, Malin SG, Holmdahl R, Lane DP, Leadbetter EA, Karlsson MCI. Proc Natl Acad Sci U S A. 2020 Apr 21;117(16):9054-9063. doi: 10.1073/pnas.1920463117.

Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks. Lundsten S, Hernández VA, Gedda L, Sarén T, Brown CJ, Lane DP, Edwards K, Nestor M. Nanomaterials (Basel). 2020 Apr 19;10(4):783. doi: 10.3390/nano10040783.

Enhancing the therapeutic effects of in vitro targeted radionuclide therapy of 3D multicellular tumor spheroids using the novel stapled MDM2/X-p53 antagonist PM2. Mortensen ACL, Morin E, Brown CJ, Lane DP, Nestor M. EJNMMI Res. 2020 Apr 16;10(1):38. doi: 10.1186/s13550-020-0613-7.

bioPROTACs as versatile modulators of intracellular therapeutic targets including proliferating cell nuclear antigen (PCNA). Lim S, Khoo R, Peh KM, Teo J, Chang SC, Ng S, Beilhartz GL, Melnyk RA, Johannes CW, Brown CJ, Lane DP, Henry B, Partridge AW. Proc Natl Acad Sci U S A. 2020 Mar 17;117(11):5791-5800. doi: 10.1073/pnas.1920251117.

A Mass-Spectrometry-Based Approach to Distinguish Annular and Specific Lipid Binding to Membrane Proteins. Bolla JR, Corey RA, Sahin C, Gault J, Hummer A, Hopper JTS, Lane DP, Drew D, Allison TM, Stansfeld PJ, Robinson CV, Landreh M. Angew Chem Int Ed Engl. 2020 Feb 24;59(9):3523-3528. doi: 10.1002/anie.201914411.

PREPRINT: Both DNA binding domains of p53 are required for its ultra-rapid recruitment to sites of UV damage. Wang YH, Ho T, Hariharan A, Goh HC, Sheetz MP, Lane, D. bioRxiv. Posted February 10, 2020. doi: 10.1101/2020.02.09.938993

Synthesis of Chiral Alkenyl Cyclopropane Amino Acids for Incorporation into Stapled Peptides. Yuen TY, Brown CJ, Tan YS, Johannes CW. J Org Chem. 2020 Feb 7;85(3):1556-1566. doi: 10.1021/acs.joc.9b02659.

Functionalized Resins for the Synthesis of Peptide Alcohols. Ferrer-Gago FJ, Koh LQ, Lane DP. Chemistry. 2020 Jan 7;26(2):379-383. doi: 10.1002/chem.201903965.

The quantification of antibody elements and receptors subunit expression using qPCR: The design of VH, VL, CH, CL, FcR subunits primers for a more holistic view of the immune system. Ling WL, Ng YL, Wipat A, Lane DP, Gan SK. J Immunol Methods. 2020 Jan;476:112683. doi: 10.1016/j.jim.2019.112683.