Victorian Centre for Functional Genomics

Quantitative subcellular reconstruction reveals a lipid mediated inter-organelle biogenesis network.

Lee RG, Rudler DL, Raven SA, Peng L, Chopin A, Moh ESX, McCubbin T, Siira SJ, Fagan SV, DeBono NJ, Stentenbach M, Browne J, Rackham FF, Li J, Simpson KJ, Marcellin E, Packer NH, Reid GE, Padman BS, Rackham O, Filipovska A.Nat Cell Biol. 2024 Jan;26(1):57-71. doi: 10.1038/s41556-023-01297-4. Epub 2023 Dec 21.

Perspectives on phenotypic screening-Screen Design and Assay Technology Special Interest Group.

Pak C, Simpson KJ, Weston AD, Cvijic ME, Evans K, Napper AD. SLAS Discov. 2024 Mar;29(2):100146. doi: 10.1016/j.slasd.2024.02.001.

Hit-to-lead optimization of 2-aminoquinazolines as anti-microbial agents against Leishmania donovani.

Das N, Roy J, Patra B, Saunders E, Sarkar D, Goon S, Sinha BP, Roy S, Roy S, Sarif J, Bandopadhyay P, Barik S, Mukherjee S, McNamara N, Varghese S, Simpson K, Baell J, McConville M, Ganguly D, Talukdar A. Eur J Med Chem. 2024 Apr 5;269:116256. doi: 10.1016/j.ejmech.2024.116256. 

Co-targeting BET, CBP, and p300 inhibits neuroendocrine signalling in androgen receptor-null prostate cancer.

Choo N, Keerthikumar S, Ramm S, Ashikari D, Teng L, Niranjan B, Hedwards S, Porter LH, Goode DL, Simpson KJ, Taylor RA, Risbridger GP, Lawrence MG. J Pathol. 2024 Jun;263(2):242-256. doi: 10.1002/path.6280. 

miR-99b-5p, miR-380-3p, and miR-485-3p are novel chemosensitizing miRNAs in high-risk neuroblastoma.

Holliday H, Yang J, Dodson E, Nikolic I, Kamili A, Wheatley M, Deng N, Alexandrou S, Davis TP, Kavallaris M, Caldon CE, McCarroll J, De Preter K, Mestdagh P, Marshall GM, Simpson KJ, Fletcher J, Swarbrick A.

Mol Ther. 2024 Jun 5;32(6):2031-2033. doi: 10.1016/j.ymthe.2024.05.008.

Quantitative subcellular reconstruction reveals a lipid mediated inter-organelle biogenesis network. Lee RG, Rudler DL, Raven SA, Peng L, Chopin A, Moh ESX, McCubbin T, Siira SJ, Fagan SV, DeBono NJ, Stentenbach M, Browne J, Rackham FF, Li J, Simpson KJ, Marcellin E, Packer NH, Reid GE, Padman BS, Rackham O, Filipovska A.Nat Cell Biol. 2024 Jan;26(1):57-71. doi: 10.1038/s41556-023-01297-4. Epub 2023 Dec 21.

A genome-wide CRISPR/Cas9 screen identifies DNA-PK as a sensitiser to ¹⁷⁷Lutetium-DOTA-octreotate radionuclide therapy. Waldeck K, Van Zuylekom J, Cullinane C, Gulati T, Simpson KJ, Tothill RW, Blyth B, Hicks RJ.Theranostics. 2023 Aug 28;13(14):4745-4761. doi: 10.7150/thno.84628. eCollection 2023.

INX-315, a selective CDK2 inhibitor, induces cell cycle arrest and senescence in solid tumors. Dietrich C, Trub A, Ahn A, Taylor M, Ambani K, Chan KT, Lu KH, Mahendra CA, Blyth C, Coulson R, Ramm S, Watt AC, Matsa SK, Bisi J, Strum J, Roberts P, Goel S.Cancer Discov. 2023 Dec 4. doi: 10.1158/2159-8290.CD-23-0954.

A semi-automated pipeline for quantifying drusen-like deposits in human induced pluripotent stem cell-derived retinal pigment epithelium cells. Hall J, Daniszewski M, Cheung S, Shobhana K, Kumar H, Liang HH, Beetham H, Cho E, Abbott C, Hewitt AW, Simpson KJ, Guymer RH, Paull D, Pébay A, Lidgerwood GE.SLAS Technol. 2023 Aug 30:S2472-6303(23)00055-9. doi: 10.1016/j.slast.2023.08.006.

Using a Quantitative High-Throughput Screening Platform to Identify Molecular Targets and Compounds as Repurposing Candidates for Endometriosis. Churchill ML, Holdsworth-Carson SJ, Cowley KJ, Luu J, Simpson KJ, Healey M, Rogers PAW, Donoghue JF. Biomolecules. 2023 Jun 8;13(6):965. doi: 10.3390/biom13060965.

Distinct assemblies of heterodimeric cytokine receptors govern stemness programs in leukemia. Kan WL, Dhagat U, Kaufmann KB, Hercus TR, Nero TL, Zeng AG, Toubia J, Barry EF, Broughton SE, Gomez GA, Benard BA, Dottore M, Cheung Tung Shing KS, Boutzen H, Samaraweera SE, Simpson KJ, Jin L, Goodall GJ, Begley CG, Thomas D, Ekert PG, Tvorogov D, D'Andrea RJ, Dick JE, Parker MW, Lopez AF.Cancer Discov. 2023 May 16:CD-22-1396. doi: 10.1158/2159-8290.CD-22-1396. Online ahead of print.

MAC-Seq: Coupling Low-Cost, High-Throughput RNA-Seq with Image-Based Phenotypic Screening in 2D and 3D Cell Models. Li XM, Yoannidis D, Ramm S, Luu J, Arnau GM, Semple T, Simpson KJ.Methods Mol Biol. 2023;2691:279-325. doi: 10.1007/978-1-0716-3331-1_22.

Radiation therapy attenuates lymphatic vessel repair by reducing VEGFR-3 signalling. Pillay V, Shukla L, Herle P, Maciburko S, Bandara N, Reid I, Morgan S, Yuan Y, Luu J, Cowley KJ, Ramm S, Simpson KJ, Achen MG, Stacker SA, Shayan R, Karnezis T.Front Pharmacol. 2023 Apr 28;14:1152314. doi: 10.3389/fphar.2023.1152314. eCollection 2023.

COMMD3 loss drives invasive breast cancer growth by modulating copper homeostasis. Hancock JL, Kalimutho M, Straube J, Lim M, Gresshoff I, Saunus JM, Lee JS, Lakhani SR, Simpson KJ, Bush AI, Anderson RL, Khanna KK.J Exp Clin Cancer Res. 2023 Apr 18;42(1):90. doi: 10.1186/s13046-023-02663-8.

The pseudokinase NRBP1 activates Rac1/Cdc42 via P-Rex1 to drive oncogenic signalling in triple-negative breast cancer. Yang X, Cruz MI, Nguyen EV, Huang C, Schittenhelm RB, Luu J, Cowley KJ, Shin SY, Nguyen LK, Lim Kam Sian TCC, Clark KC, Simpson KJ, Ma X, Daly RJ.Oncogene. 2023 Jan 24. doi: 10.1038/s41388-023-02594-w

High-Throughput Live and Fixed Cell Imaging Method to Screen Matrigel-Embedded Organoids. Ramm S, Vary R, Gulati T, Luu J, Cowley KJ, Janes MS, Radio N, Simpson KJ. Organoids 2023, 2(1), 1-19; https://doi.org/10.3390/organoids2010001 

Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway. Hannan KM, Soo P, Wong MS, Lee JK, Hein N, Poh P, Wysoke KD, Williams TD, Montellese C, Smith LK, Al-Obaidi SJ, Núñez-Villacís L, Pavy M, He JS, Parsons KM, Loring KE, Morrison T, Diesch J, Burgio G, Ferreira R, Feng ZP, Gould CM, Madhamshettiwar PB, Flygare J, Gonda TJ, Simpson KJ, Kutay U, Pearson RB, Engel C, Watkins NJ, Hannan RD, George AJ.Cell Rep. 2022 Nov 1;41(5):111571. doi: 10.1016/j.celrep.2022.111571. 

Functional high-throughput screen identifies microRNAs that promote butyrate-induced death in colorectal cancer cells. Ali SR, Humphreys KJ, Simpson KJ, McKinnon RA, Meech R, Michael MZ.Mol Ther Nucleic Acids. 2022 Aug 29;30:30-47. doi: 10.1016/j.omtn.2022.08.037 

Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction. Fujihara KM, Zhang BZ, Jackson TD, Ogunkola MO, Nijagal B, Milne JV, Sallman DA, Ang CS, Nikolic I, Kearney CJ, Hogg SJ, Cabalag CS, Sutton VR, Watt S, Fujihara AT, Trapani JA, Simpson KJ, Stojanovski D, Leimkühler S, Haupt S, Phillips WA, Clemons NJ.Sci Adv. 2022 Sep 16;8(37):eabm9427. doi: 10.1126/sciadv.abm9427 

Epigenetic modulators of B cell fate identified through coupled phenotype-transcriptome analysis. Kong IY, Trezise S, Light A, Todorovski I, Arnau GM, Gadipally S, Yoannidis D, Simpson KJ, Dong X, Whitehead L, Tempany JC, Farchione AJ, Sheikh AA, Groom JR, Rogers KL, Herold MJ, Bryant VL, Ritchie ME, Willis SN, Johnstone RW, Hodgkin PD, Nutt SL, Vervoort SJ, Hawkins ED.Cell Death Differ. 2022 Dec;29(12):2519-2530. doi: 10.1038/s41418-022-01037-5 

Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAFV600 melanoma. Smith LK, Parmenter T, Kleinschmidt M, Kusnadi EP, Kang J, Martin CA, Lau P, Patel R, Lorent J, Papadopoli D, Trigos A, Ward T, Rao AD, Lelliott EJ, Sheppard KE, Goode D, Hicks RJ, Tiganis T, Simpson KJ, Larsson O, Blythe B, Cullinane C, Wickramasinghe VO, Pearson RB, McArthur GA.Nat Commun. 2022 Mar 1;13(1):1100. doi: 10.1038/s41467-022-28705-x. 

miR-99b-5p, miR-380-3p, and miR-485-3p are novel chemosensitizing miRNAs in high-risk neuroblastoma. Holliday H, Yang J, Dodson E, Nikolic I, Kamili A, Wheatley M, Deng N, Alexandrou S, Davis TP, Kavallaris M, Caldon CE, McCarroll J, De Preter K, Mestdagh P, Marshall GM, Simpson KJ, Fletcher J, Swarbrick A.Mol Ther. 2022 Mar 2;30(3):1119-1134. doi: 10.1016/j.ymthe.2022.01.004. Epub 2022 Jan 5.

High-Throughput Imaging Assay for Drug Screening of 3D Prostate Cancer Organoids. Choo N, Ramm S, Luu J, Winter JM, Selth LA, Dwyer AR, Frydenberg M, Grummet J, Sandhu S, Hickey TE, Tilley WD, Taylor RA, Risbridger GP, Lawrence MG, Simpson KJ.SLAS Discov. 2021 Oct;26(9):1107-1124. doi: 10.1177/24725552211020668. Epub 2021 Jun 11. 

Phenotypic Consequences of SLC25A40-ABCB1 Fusions beyond Drug Resistance in High-Grade Serous Ovarian Cancer. Pishas KI, Cowley KJ, Pandey A, Hoang T, Beach JA, Luu J, Vary R, Smith LK, Shembrey CE, Rashoo N, White MO, Simpson KJ, Bild A, Griffiths JI, Cheasley D, Campbell I, Bowtell DDL, Christie EL.Cancers (Basel). 2021 Nov 11;13(22):5644. doi: 10.3390/cancers13225644. 

The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer. Vervoort SJ, Welsh SA, Devlin JR, Barbieri E, Knight DA, Offley S, Bjelosevic S, Costacurta M, Todorovski I, Kearney CJ, Sandow JJ, Fan Z, Blyth B, McLeod V, Vissers JHA, Pavic K, Martin BP, Gregory G, Demosthenous E, Zethoven M, Kong IY, Hawkins ED, Hogg SJ, Kelly MJ, Newbold A, Simpson KJ, Kauko O, Harvey KF, Ohlmeyer M, Westermarck J, Gray N, Gardini A, Johnstone RW.Cell. 2021 Jun 10;184(12):3143-3162.e32. doi: 10.1016/j.cell.2021.04.022. Epub 2021 May 17. 

CX-5461 Sensitizes DNA Damage Repair-proficient Castrate-resistant Prostate Cancer to PARP Inhibition. Lawrence MG, Porter LH, Choo N, Pook D, Grummet JP, Pezaro CJ, Sandhu S, Ramm S, Luu J, Bakshi A, Goode DL, Sanij E, Pearson RB, Hannan RD, Simpson KJ, Taylor RA, Risbridger GP, Furic L.Mol Cancer Ther. 2021 Nov;20(11):2140-2150. doi: 10.1158/1535-7163.MCT-20-0932. Epub 2021 Aug 19.PMID: 34413130 

High-content siRNA 3D co-cultures to identify myoepithelial cell-derived breast cancer suppressor proteins. Duivenvoorden HM, Brockwell NK, Nowell CJ, Simpson KJ, Parker BS. Sci Data. 2021 May 28;8(1):147. doi: 10.1038/s41597-021-00924-9. 

Genome-wide genetic screen identifies host ubiquitination as important for Legionella pneumophila Dot/Icm effector translocation. Ong SY, Schuelein R, Wibawa RR, Thomas DW, Handoko Y, Freytag S, Bahlo M, Simpson KJ, Hartland EL.Cell Microbiol. 2021 Oct;23(10):e13368. doi: 10.1111/cmi.13368. Epub 2021 Jun 8.

Genes regulating membrane-associated E-cadherin and proliferation in adenomatous polyposis coli mutant colon cancer cells: High content siRNA screen. King LE, Zhang HH, Gould CM, Thomas DW, Whitehead LW, Simpson KJ, Burgess AW, Faux MC.PLoS One. 2020 Oct 15;15(10):e0240746. doi: 10.1371/journal.pone.0240746. eCollection 2020. 

Genome-wide RNAi screen for genes regulating glycolytic response to vemurafenib in BRAFV600 melanoma cells. Smith LK, Parmenter T, Gould CM, Madhamshettiwar PB, Sheppard KE, Simpson KJ, McArthur GA.Sci Data. 2020 Oct 12;7(1):339. doi: 10.1038/s41597-020-00683-z. 

Loss of HPV type 16 E7 restores cGAS-STING responses in human papilloma virus-positive oropharyngeal squamous cell carcinomas cells. Bortnik V, Wu M, Julcher B, Salinas A, Nikolic I, Simpson KJ, McMillan NA, Idris A.J Microbiol Immunol Infect. 2021 Aug;54(4):733-739. doi: 10.1016/j.jmii.2020.07.010. Epub 2020 Jul 30. 

GRB7 is an oncogenic driver and potential therapeutic target in oesophageal adenocarcinoma. Gotovac JR, Liu DS, Yates MJ, Milne JV, Macpherson AA, Simpson KJ, Eslick GD, Mitchell C, Duong CP, Phillips WA, Clemons NJ.J Pathol. 2020 Nov;252(3):317-329. doi: 10.1002/path.5528. Epub 2020 Sep 15. 

Methodology for the identification of small molecule inhibitors of the Fanconi Anaemia ubiquitin E3 ligase complex. Sharp MF, Murphy VJ, Twest SV, Tan W, Luu J, Simpson KJ, Deans AJ, Crismani W.Sci Rep. 2020 May 14;10(1):7959. doi: 10.1038/s41598-020-64868-7. 

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