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Repurposing FDA-approved drugs to inhibit PRL-3, Scientific Reports, 2021

A major goal of our lab’s PRL-3 projects is to find a way to inhibit PRL-3 activity. PRL-3 is essential for the growth and spread of many types of cancer, so if we can find a way to block PRL-3, we could potentially impact many patients. However, the drugs used to target PRL-3 are still…

Methods for high-throughput drug screens of human cancer cells in zebrafish. JoVE, 2020

Meghan and Henry have starred in a JoVE (Journal of Visualized Experiments) video article explaining how the lab transplants human cancer cells into zebrafish and uses them for high-throughput drug screening. The benefit of this xenograft model is that we can rapidly screen though hundreds of compounds in living animals, which allows us to find…

The phosphatase PRL-3 drives ALL progression, Oncogenesis 2020

The lab’s first research manuscript is out! Min’s research defined the oncogenic role of PRL-3 phosphatase in T-cell acute lymphoblastic leukemia (T-ALL), which is a very progressive pediatric cancer and lacks targeted therapies. Our findings show that PRL-3 promotes T-ALL development/onset in zebrafish models and plays a role in engraftment in mouse xenograft models. Cell-culture…

All Publications

Chernyavskaya Y, Zhang X, Liu J, Blackburn J. Long-read sequencing of the zebrafish genome reorganizes genomic architecture. BMC Genomics. 2022 Feb 10;23(1):116. doi: 10.1186/s12864-022-08349-3. PMID: 35144548; PMCID: PMC8832730. [Full Text]

Smith, C.N. and Blackburn, J.S. (2021), PRL-3 promotes a positive feedback loop between STAT1/2-induced gene expression and glycolysis in multiple myeloma. FEBS J. [Full Text]

Rivas DR, Dela Cerna MVC, Smith CN, Sampathi S, Patty BG, Lee D, Blackburn JS. A screen of FDA-approved drugs identifies inhibitors of protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3). Sci Rep. 2021 May 13;11(1):10302. doi: 10.1038/s41598-021-89668-5. [Full Text]

Haney MG, Wimsett M, Liu C, Blackburn JS. Protocol for rapid assessment of the efficacy of novel Wnt inhibitors using zebrafish models. STAR Protoc. 2021 Apr 1;2(2):100433. doi: 10.1016/j.xpro.2021.100433. [PMC Link]

Zhang W, Sviripa VM, Xie Y, Yu T, Haney MG, Blackburn JS, Adeniran CA, Zhan CG, Watt DS, Liu C. Epigenetic Regulation of Wnt Signaling by Carboxamide-Substituted Benzhydryl Amines that Function as Histone Demethylase Inhibitors. iScience. 2020 Nov 13;23(12):101795. doi: 10.1016/j.isci.2020.101795. [Full Text]

Garcia EG, Veloso A, Oliveira ML, Allen JR, Loontiens S, Brunson D, Do D, Yan C, Morris R, Iyer S, Garcia SP, Iftimia N, Van Loocke W, Matthijssens F, McCarthy K, Barata JT, Speleman F, Taghon T, Gutierrez A, Van Vlierberghe P, Haas W, Blackburn JS, Langenau DM. PRL3 enhances T-cell acute lymphoblastic leukemia growth through suppressing T-cell signaling pathways and apoptosis. Leukemia. 2021 Mar;35(3):679-690. doi: 10.1038/s41375-020-0937-3. Epub 2020 Jun 30. [Full Text]

Haney MG, Moore LH, Blackburn JS. Drug Screening of Primary Patient Derived Tumor Xenografts in ZebrafishJ Vis Exp2020 Apr 10;(158)doi: 10.3791/60996. [PubMed Link]

Wei M, Haney MG, Rivas DR, Blackburn JS. Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) drives migration and progression of T-cell acute lymphoblastic leukemia in vitro and in vivo. Oncogenesis. 2020, 9(1):6. [PubMed Link] [Full Text]

Xie Y, Kril LM, Zhang W, Bondarenko SP, Kondratyuk KM, Hausman ES, Martin ZM, Wyrebek PP, Liu X, Deacuic A, Dowskin LP, Chen J, Zhu H, Zhan CG, Sviripa VM, Blackburn J, Watt DS, Liu C. Semisynthetic aurones inhibit tubulin polymerization at the colchicine-binding site and repress PC-3 tumor xenografts in nude mice and myc-induced T-ALL in zebrafish. Science Reports. 2019, 9(1):6439.  [PubMed Link] [Full Text]

Wei M, Korotkov KV, Blackburn JS. Targeting phosphatases of regenerating liver (PRLs) in cancer. Pharmacology and Therapeutics. 2018; Oct(190) 128-138. [PubMed Link] [Full Text]

Lobbardi R, Pinder J, Martinze-Pastor B, Blackburn JS, Abraham B, Langenau DM. Tox is an oncogeneic driver in T-cell Acute Lymphoblastic Leukemia. Cancer Discovery. 2017; 7(11) 1336-1353. [PubMed Link] [Full Text]

Moore, F.E.;Garcia, E.G.;Lobbardi, R.;Jain, E.;Tang, Q.;Moore, J.C.;Cortes, M.;Molodtsov, A.;Kasheta, M.;Luo, C.C.;Garcia, A.J.;Mylvaganam, R.;Yoder, J.A.;Blackburn, J.S.;Sadreyev, R.I.;Ceol, C.J.;North, T.E.;Langenau, D.M. “Single-cell transcriptional analysis of normal, aberrant, and malignant hematopoiesis in zebrafish.” The Journal of experimental medicine 213, 6 (2016): 979-92. [PubMed Link] | [Full Text]

Tang, Q.;Moore, J.C.;Ignatius, M.S.;Tenente, I.M.;Hayes, M.N.;Garcia, E.G.;Torres Yordán, N.;Bourque, C.;He, S.;Blackburn, J.S.;Look, A.T.;Houvras, Y.;Langenau, D.M. “Imaging tumour cell heterogeneity following cell transplantation into optically clear immune-deficient zebrafish.” Nature communications 7,(2016): 10358. [PubMed Link] | [Full Text]

Blackburn, J.S.;Liu, S.;Wilder, J.L.;Dobrinski, K.P.;Lobbardi, R.;Moore, F.E.;Martinez, S.A.;Chen, E.Y.;Lee, C.;Langenau, D.M. “Clonal evolution enhances leukemia-propagating cell frequency in T cell acute lymphoblastic leukemia through Akt/mTORC1 pathway activation.” Cancer cell 25, 3 (2014): 366-78. [PubMed Link] | [Full Text]

Blackburn, J.S.;Langenau, D.M. “Zebrafish as a model to assess cancer heterogeneity, progression and relapse.” Disease models & mechanisms 7, 7 (2014): 755-62. [PubMed Link] | [Full Text]

Tang, Q.;Abdelfattah, N.S.;Blackburn, J.S.;Moore, J.C.;Martinez, S.A.;Moore, F.E.;Lobbardi, R.;Tenente, I.M.;Ignatius, M.S.;Berman, J.N.;Liwski, R.S.;Houvras, Y.;Langenau, D.M. “Optimized cell transplantation using adult rag2 mutant zebrafish.” Nature methods 11, 8 (2014): 821-4. [PubMed Link] | [Full Text]

Blackburn, J.S.;Liu, S.;Raiser, D.M.;Martinez, S.A.;Feng, H.;Meeker, N.D.;Gentry, J.;Neuberg, D.;Look, A.T.;Ramaswamy, S.;Bernards, A.;Trede, N.S.;Langenau, D.M. “Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency.” Leukemia 26, 9 (2012): 2069-78. [PubMed Link] | [Full Text]

Ignatius, M.S.;Chen, E.;Elpek, N.M.;Fuller, A.Z.;Tenente, I.M.;Clagg, R.;Liu, S.;Blackburn, J.S.;Linardic, C.M.;Rosenberg, A.E.;Nielsen, P.G.;Mempel, T.R.;Langenau, D.M. “In vivo imaging of tumor-propagating cells, regional tumor heterogeneity, and dynamic cell movements in embryonal rhabdomyosarcoma.”Cancer cell 21, 5 (2012): 680-93. [PubMed Link] | [Full Text]

Zheng, S.;Ghitani, N.;Blackburn, J.S.;Liu, J.P.;Zeitlin, S.O. “A series of N-terminal epitope tagged Hdh knock-in alleles expressing normal and mutant huntingtin: their application to understanding the effect of increasing the length of normal Huntingtin’s polyglutamine stretch on CAG140 mouse model pathogenesis.” Molecular brain 5, (2012): 28. [PubMed Link] | [Full Text]

Moore, F.E.;Reyon, D.;Sander, J.D.;Martinez, S.A.;Blackburn, J.S.;Khayter, C.;Ramirez, C.L.;Joung, J.K.;Langenau, D.M. “Improved somatic mutagenesis in zebrafish using transcription activator-like effector nucleases (TALENs).” PloS one 7, 5 (2012): e37877. [PubMed Link] | [Full Text]

Blackburn, J.S.;Liu, S.;Langenau, D.M. “Quantifying the frequency of tumor-propagating cells using limiting dilution cell transplantation in syngeneic zebrafish.” Journal of visualized experiments : JoVE 53(2011): e2790. [PubMed Link] | [Full Text]

Sander, J.D.;Dahlborg, E.J.;Goodwin, M.J.;Cade, L.;Zhang, F.;Cifuentes, D.;Curtin, S.J.;Blackburn, J.S.;Thibodeau-Beganny, S.;Qi, Y.;Pierick, C.J.;Hoffman, E.;Maeder, M.L.;Khayter, C.;Reyon, D.;Dobbs, D.;Langenau, D.M.;Stupar, R.M.;Giraldez, A.J.;Voytas, D.F.;Peterson, R.T.;Yeh, J.R.;Joung, J.K.“Selection-free zinc-finger-nuclease engineering by context-dependent assembly (CoDA).” Nature methods 8, 1 (2011): 67-9. [PubMed Link] | [Full Text]

Blackburn, J.S.;Liu, S.;Raimondi, A.R.;Ignatius, M.S.;Salthouse, C.D.;Langenau, D.M. “High-throughput imaging of adult fluorescent zebrafish with an LED fluorescence macroscope.” Nature protocols 6, 2(2011): 229-41. [PubMed Link] | [Full Text]

Blackburn, J.S.;Langenau, D.M. “aMAZe-ing tools for mosaic analysis in zebrafish.” Nature methods 7, 3(2010): 188-90. [PubMed Link] | [Full Text]

Smith, A.C.;Raimondi, A.R.;Salthouse, C.D.;Ignatius, M.S.;Blackburn, J.S.;Mizgirev, I.V.;Storer, N.Y.;Jong, J.L.;Chen, A.T.;Zhou, Y.;Revskoy, S.;Zon, L.I.;Langenau, D.M. “High-throughput cell transplantation establishes that tumor-initiating cells are abundant in zebrafish T-cell acute lymphoblastic leukemia.” Blood 115, 16 (2010): 3296-303. [PubMed Link] | [Full Text]

Eck, S.M.;Blackburn, J.S.;Schmucker, A.C.;Burrage, P.S.;Brinckerhoff, C.E. “Matrix metalloproteinase and G protein coupled receptors: co-conspirators in the pathogenesis of autoimmune disease and cancer.” Journal of autoimmunity 33, 3-4 (2009): 214-21. [PubMed Link] | [Full Text]

Blackburn, J.S.;Brinckerhoff, C.E. “Wild-type versus mutant MMP-8 in melanoma: ‘when you come to a fork in the road, take it’.” Pigment cell & melanoma research 22, 3 (2009): 248-50. [PubMed Link] | [Full Text]

Blackburn, J.S.;Liu, I.;Coon, C.I.;Brinckerhoff, C.E. “A matrix metalloproteinase-1/protease activated receptor-1 signaling axis promotes melanoma invasion and metastasis.” Oncogene 28, 48 (2009): 4237-48. [PubMed Link] | [Full Text]

Blackburn, J.S.;Brinckerhoff, C.E. “Matrix metalloproteinase-1 and thrombin differentially activate gene expression in endothelial cells via PAR-1 and promote angiogenesis.” The American journal of pathology173, 6 (2008): 1736-46. [PubMed Link] | [Full Text]

Blackburn, J.S.;Rhodes, C.H.;Coon, C.I.;Brinckerhoff, C.E. “RNA interference inhibition of matrix metalloproteinase-1 prevents melanoma metastasis by reducing tumor collagenase activity and angiogenesis.” Cancer research 67, 22 (2007): 10849-58. [PubMed Link] | [Full Text]

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