Dr Jenny Wang
Conjoint Senior Lecturer

Dr Jenny Wang

Medicine & Health
School of Clinical Medicine
  • Group Leader, Children's Cancer Institute, UNSW, 2013-present
  • Research Fellow, Harvard Medical School, USA, 2005-2011

Dr Jenny Wang is Head of the Cancer and Stem Cell Laboratory. She returned to Sydney in 2011 from Harvard Medical School, where she undertook postdoctoral research in leukemia stem cell biology. The main focus of her laboratory is to develop novel therapies targeting malignant stem cells that are often resistant to chemotherapy and that are now believed to be the root cause of treatment failure and relapse in cancer.

Stem cells have become the centre of much attention because they are capable of dividing indefinitely to produce new copies of themselves (self-renewal) and also generating multiple cell types. Genetic and epigenetic abnormalities enable malignant stem cells to hijack normal stem cell self-renewal mechanisms that multiply out of control, causing cancer and to evade treatment and regenerate new tumors through their self-renewal capacity. Targeted disruption of aberrant self-renewal represents a novel therapeutic strategy that can significantly reduce the capacity of a tumor to regenerate itself after treatment and is becoming a central focus in new drug development.

Targeted therapyhttps://www.news-medical.net/news/20200621/Researchers-discover-new-and-improved-way-to-treat-poor-prognosis-blood-cancer.aspx

Current Funding Sources
National Health and Medical Research Council (NHMRC)
Leukemia Foundation
Cancer Australia
Tour de Cure

Research goals
To understand the biology of cancer stem cells
To identify critical drug targets for malignant stem cell eradication
To develop effective therapies to treat poor-prognosis leukemia 

Project opportunities - PhD, Masters and Honours 

Targeting of leukemia stem cells for the development of curative therapies
Acute myeloid leukemia (AML) is a difficult-to-treat blood cancer with a 5-year survival rate of only 27% in Australia. Despite intensive chemotherapy, the majority of patients with AML relapse and ultimately die from their disease. Clinical evidence has supported the important role of leukemia stem cells in the high relapse rate of AML patients. Leukemia stem cells reside in a mostly quiescent state and as such they are resistant to chemotherapy. These cells possess several unique features such as self-renewal and escaping from cell death. Targeted elimination of leukemia stem cells is now believed to be essential for AML patients to achieve a complete remission. Our studies have identified key self-renewal pathways (Science 2010; Blood 2014; Leukemia 2016; Cancer Cell 2020) for stem cell formation and our exciting new findings of pathway inhibitors provide promising therapeutic opportunities to specifically target leukemia stem cells. This project is designed to understand the mechanisms of action of pathway inhibitors in order to develop effective stem cell-targeted therapies for aggressive AML.

Epigenetic regulation of leukemia stem cells - developing new epigenetic therapies
Epigenetic regulation of gene expression plays crucial roles in stem cell functions. Inappropriate maintenance of epigenetic ‘marks’ - that sit on the nuclear DNA of cancer cells and control the activity of genes - results in activation of oncogenic self-renewal pathways leading to the formation of leukemia stem cells and the subsequent development of leukemia. Unlike genetic alterations, epigenetic marks can be reversed by treatments with chromatin-modifying drugs, making them suitable targets for epigenetic-based therapies. Our studies have identified several new epigenetic regulators that contribute to leukemia formation and progression. This project aims at exploring epigenetic mechanisms that govern leukemia stem cell function and at discovering chromatin-modifying drugs that are capable of reversing leukemia-associated epigenetic marks. The outcome of this study will have the potential to develop novel epigenetic therapies.  

Developing RNA-based therapeutics to eradicate leukemia stem cells
The recent discovery of non-coding RNAs (ncRNAs) has dramatically altered our view of gene regulation in cancer. NcRNAs serve as regulatory molecules, playing a pivotal role in cancer progression and metastasis. Long ncRNAs (lncRNAs) are defined as non-protein coding transcripts longer than 200 nucleotides and have demonstrated oncogenic or tumor suppressive capabilities. We have identified several novel lncRNAs in leukemia stem cells. This study will discover the mechanism of novel lncRNAs in driving oncogenesis and develop RNA-based therapeutics for aggressive AML.

Techniques: Cell-based assays, drug response assays, molecular biology, proteomics, immunofluorescence, gene editing, single-cell RNA-seq and CITE-seq, ChIP-seq, microarray, flow cytometry, patient-derived xenograft mouse models and in vivo drug testing, etc.

Significance: Successful completion of these projects will generate new insights into cancer stem cell biology, identify novel therapeutic targets, and provide preclinical validation of therapeutic potential. These studies therefore have the potential to lead to the development of novel therapies that directly and selectively kill cancer stem cells, which are now considered to be the root cause of disease progression, tumor resistance to chemotherapy, and ultimate relapse.

Selected Publications

  • Salik BYi HHassan NSantiappillai N Vick BConnerty P Duly ATrahair TWoo AJBeck DLiu TSpiekermann KJeremias IWang JKavallaris MHaber MNorris MDLiebermann DAD'Andrea RJMurriel CWang JY (2020) Targeting RSPO3-LGR4 signaling for leukemia stem cell eradication in acute myeloid leukemia. Cancer Cell. 2020. 38(2):263-278. (IF 31.74)  

  • Teng L, Feng YC, Guo ST, Wang PL, Wang SX, Zhang SN, Qi TF, La T, Zhang YY, Zhao XH, Zhang D, Wang JY, Shi Y, Li JM, Cao H, Liu T, Thorne RF, Jin L, Shao F, Zhang XD (2021) The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis. Nature Communications. 2021. 12(1):3734. (IF 14.91)
  • Chen J, Nelson C, Wong M, Tee AE, Liu PY, La T, Fletcher JI, Kamili A, Mayoh C, Bartenhagen C, Trahair TN, Xu N, Jayatilleke N, Wong-Erasmus M, Peng H, Atmadibrata B, Cheung BB, Lan Q, Bryan TM, Mestdagh P, Vandesompele J, Combaret V, Boeva V, Wang JY, Janoueix-Lerosey I, Cowley MJ, MacKenzie KL, Dolnikov A, Li J, Polly P, Marshall GM, Reddel RR, Norris MD, Haber M, Fischer M, Zhang XD, Pickett HA, Liu T (2021) Targeted therapy of TERT-rearranged neuroblastoma with BET bromodomain inhibitor and proteasome inhibitor combination therapy. Clinical Cancer Research. 2021. 27(5):1438-1451. (IF 12.53)
  • Lan Q, Liu PY, Bell JL, Wang JY, Hüttelmaier S, Zhang XD, Zhang L, Liu T (2021) The emerging roles of RNA m6A methylation and demethylation as critical regulators of tumorigenesis, drug sensitivity, and resistance. Cancer Research. 2021. doi:10.1158/0008-5472.CAN-20-4107. (IF 12.7)
  • Hassan N, Yang J, Wang JY (2020) An improved protocol for establishment of AML patient-derived xenograft models. STAR Protocols. 2020. 1(3):100156. doi.org/10.1016/j.xpro.2020.100156. 
  • Yang J, Hassan N, Chen SXF, Datuin J, Wang JY (2020) Self-renewal pathways in acute myeloid leukemia stem cells. In Pier Paolo Piccaluga (Ed.), Acute Leukemias. Rijeka, Croatia: InTech Publishers. Book Chapter. Doi: 10.5772/intechopen.94379. In press.  
  • Lynch JR, Salik B, Connerty P, Vick B, Leung H, Pijning A, Jeremias I, Spiekermann K, Trahair T, Liu T, Haber M, Norris MD, Woo AJ, Hogg P, Wang J, Wang JY (2019) JMJD1C-mediated metabolic dysregulation contributes to HOXA9-dependent leukemogenesis. Leukemia. 2019. 33:1400-1410. (IF 11.52)
  • Gonzales-Aloy E, Connerty P, Salik B, Liu B, Woo AJ, Haber M, Norris MD, Wang J, Wang JY. (2019) miR-101 suppresses the development of MLL-rearranged acute myeloid leukemia. Haematologica. 2019. 104:296-299. (IF 9.94)
  • Wong M, Sun Y, Xi Z, Milazzo G, Poulos RC, Bartenhagen C, Bell JL, Mayoh C, Ho N, Tee AE, Chen X, Li Y, Ciaccio R, Liu PY, Jiang CC, Lan Q, Jayatilleke N, Cheung BB, Haber M, Norris MD, Zhang XD, Marshall GM, Wang JY, Hüttelmaier S, Fischer M, Wong JWH, Xu H, Giovanni Perini, Qihan Dong, George RE, Liu T (2019) JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma. Nature Communications. 2019. 10:3319. (IF 14.91)
  • Liu P, Tee A, Milazzo G, Hannan K, Maag J, Mondal S, Atmadibrata B, Bartonicek N, Peng H, Ho N, Mayoh CM, Ciaccio R, Sun Y, Henderson M, Gao J, Everaert C, Hulme A, Wong M, Lan Q, Cheung B, Shi L, Wang JY, Simon T, Fischer M, Zhang XD, Marshall G, Norris M, Haber M, Vandesompele J, Li J, Mestdagh P, Hannan R, Dinger M, Perini G, Liu T (2019) The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35. Nature Communications. 2019. 10:5026. (IF 14.91)
  • Woo AJ, Patry C, Ghamari A, Pregernig G, Zheng K, Piers T, Hibbs M, Li JK, Fidalgo M, Wang JY, Lee J, Leedman PJ, Wang J, Fraenkel E, Cantor AB (2019) Zfp281 (ZBP-99) plays a functionally redundant role with Zfp148 (ZBP-89) during erythroid development. Blood Advances. 2019. 3:2499-2511. (IF 6.86)
  • Wong MK, Tee AE, Milazzo G, Bell JL, Poulos RC, Atmadibrata B, Sun Y, Jing D, Ho N, Ling D, Liu PY, Zhang XD, Hüttelmaier S, Wong JW, Wang JY, Polly P, Perini G, Scarlett CJ, Liu T (2017) The histone methyltransferase DOT1L promotes neuroblastoma by regulating gene transcription. Cancer Research. 2017. 77:2522-2533. (IF 12.7)
  • Sun Y, Atmadibrata B, Yu D, Wong MKK, Liu B, Ho N, Ling D, Tee AE, Wang JY, Mungrue IN, Liu PY, Liu T. (2017) Up-regulation of LYAR induces neuroblastoma cell proliferation and survival. Cell Death & Differentiation. 2017. 24:1645-1654. (IF 10.71)
  • Lynch JR, Yi H, Casolari DA, Voli F, Gonzales-Aloy E, Fung TK, Liu B, Brown A, Liu T, Haber M, Norris MD, Lewis ID, So CWE, D’Andrea RJ, Wang JY (2016) Gaq signaling is required for the maintenance of MLL-AF9 induced acute myeloid leukemia. Leukemia. 2016. 30:1745-1748. (IF 11.52)
  • Lynch JR, Wang JY (2016) G protein-coupled receptor signaling in stem cells and cancer. Int J Mol Sci. 2016. 17:707. (IF 5.92)
  • Dietrich PA, Yang C, Leung HH, Lynch JR, Gonzales E, Liu B, Haber M, Norris MD, Wang J, Wang JY (2014) GPR84 sustains aberrant β-catenin signaling in leukemic stem cells for maintenance of MLL leukemogenesis. Blood. 2014. 124:3284-3294. (IF 22.11)
  • Lane SW*, Wang JY*, Lo Celso C*, Ragu C, Bullinger L, Sykes SM, Ferraro F, Shterental S, Lin CP, Gilliland DG, Scadden DT, Armstrong SA, Williams DA (2011) Differential niche and Wnt requirements during acute myeloid leukemia progression. Blood. 2011. 118:2849-2856. *equal contribution. (IF 22.11)
  • Wang JY, Krivtsov AV, Sinha AU, North TE, Goessling W, Feng Z, Zon LI, Armstrong SA (2010) The Wnt/β-catenin pathway is required for the development of leukemia stem cells in AML. Science. 2010. 327:1650-1653. (IF 41.84)
  • Krivtsov AV, Wang JY, Feng Z, Armstrong SA (2009) Gene expression profiling of leukemia stem cells. Methods Mol Biol. 2009. 538: 231-246. doi:10.1007/978-1-59745-418-6_11.
  • Wang JY, Armstrong SA (2008) Cancer: inappropriate expression of stem cell programs. Cell Stem Cell. 2008. 2:297-299. (IF 24.63)
  • Wang Y, Armstrong SA (2007) Genome-wide SNP analysis in cancer: leukemia shows the way. Cancer Cell. 2007. 11:308-309. (IF 31.74)
  • Krivtsov AV, Twomey D, Feng Z, Stubbs MC, Wang JY, Faber J, Levine JE, Wang J, Hahn WC, Gilliland DG, Golub TR, Armstrong SA (2006) Transformation from committed progenitor to leukaemia stem cell initiated by MLL-AF9. Nature. 2006. 442: 818–822. (IF 42.77)
Location
Lowy Cancer Research Centre G25 UNSW Medicine, University of New South Wales, Sydney, NSW 2052 Australia
  • Journal articles | 2021
    Chen J; Nelson C; Wong M; Tee AE; Liu PY; La T; Fletcher JI; Kamili A; Mayoh C; Bartenhagen C; Trahair TN; Xu N; Jayatilleke N; Wong M; Peng H; Atmadibrata B; Cheung BB; Lan Q; Bryan TM; Mestdagh P; Vandesompele J; Combaret V; Boeva V; Wang JY; Janoueix-Lerosey I; Cowley MJ; MacKenzie KL; Dolnikov A; Li J; Polly P; Marshall GM; Reddel RR; Norris MD; Haber M; Fischer M; Zhang XD; Pickett HA; Liu T, 2021, 'Targeted therapy of TERT-rearranged neuroblastoma with BET bromodomain inhibitor and proteasome inhibitor combination therapy', Clinical Cancer Research, vol. 27, pp. 1438 - 1451, http://dx.doi.org/10.1158/1078-0432.CCR-20-3044
    Journal articles | 2021
    La T; Chen S; Guo T; Zhao XH; Teng L; Li D; Carnell M; Zhang YY; Feng YC; Cole N; Brown AC; Zhang D; Dong Q; Wang JY; Cao H; Liu T; Thorne RF; Shao FM; Zhang XD; Jin L, 2021, 'Visualization of endogenous p27 and Ki67 reveals the importance of a c-Myc-driven metabolic switch in promoting survival of quiescent cancer cells', Theranostics, vol. 11, pp. 9605 - 9622, http://dx.doi.org/10.7150/THNO.63763
    Journal articles | 2021
    Lan Q; Liu PY; Bell JL; Wang JY; Hüttelmaier S; Zhang XD; Zhang L; Liu T, 2021, 'The emerging roles of RNA m6A methylation and demethylation as critical regulators of tumorigenesis, drug sensitivity, and resistance', Cancer Research, pp. canres.4107.2020 - canres.4107.2020, http://dx.doi.org/10.1158/0008-5472.can-20-4107
    Journal articles | 2021
    Teng L; Feng YC; Guo ST; Wang PL; Qi TF; Yue YM; Wang SX; Zhang SN; Tang CX; La T; Zhang YY; Zhao XH; Gao JN; Wei LY; Zhang D; Wang JY; Shi Y; Liu XY; Li JM; Cao H; Liu T; Thorne RF; Jin L; Shao FM; Zhang XD, 2021, 'The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis', Nature Communications, vol. 12, http://dx.doi.org/10.1038/s41467-021-24099-4
    Journal articles | 2020
    Salik B; Yi H; Hassan N; Santiappillai N; Vick B; Connerty P; Duly A; Trahair T; Woo AJ; Beck D; Liu T; Spiekermann K; Jeremias I; Wang J; Kavallaris M; Haber M; Norris MD; Liebermann DA; D'Andrea RJ; Murriel C; Wang JY, 2020, 'Targeting RSPO3-LGR4 Signaling for Leukemia Stem Cell Eradication in Acute Myeloid Leukemia', Cancer Cell, vol. 38, pp. 263 - 278.e6, http://dx.doi.org/10.1016/j.ccell.2020.05.014
    Journal articles | 2019
    Gonzales-Aloy E; Connerty P; Salik B; Liu B; Woo AJ; Haber M; Norris MD; Wang J; Wang JY, 2019, 'MiR-101 suppresses the development of MLL-rearranged acute myeloid leukemia', Haematologica, vol. 104, pp. e296 - e299, http://dx.doi.org/10.3324/haematol.2018.209437
    Journal articles | 2019
    Liu PY; Tee AE; Milazzo G; Hannan KM; Maag J; Mondal S; Atmadibrata B; Bartonicek N; Peng H; Ho N; Mayoh C; Ciaccio R; Sun Y; Henderson MJ; Gao J; Everaert C; Hulme AJ; Wong M; Lan Q; Cheung BB; Shi L; Wang JY; Simon T; Fischer M; Zhang XD; Marshall GM; Norris MD; Haber M; Vandesompele J; Li J; Mestdagh P; Hannan RD; Dinger ME; Perini G; Liu T, 2019, 'The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35', Nature Communications, vol. 10, pp. 5026, http://dx.doi.org/10.1038/s41467-019-12971-3
    Journal articles | 2019
    Lynch JR; Salik B; Connerty P; Vick B; Leung H; Pijning A; Jeremias I; Spiekermann K; Trahair T; Liu T; Haber M; Norris MD; Woo AJ; Hogg P; Wang J; Wang JY, 2019, 'JMJD1C-mediated metabolic dysregulation contributes to HOXA9-dependent leukemogenesis', Leukemia, vol. 33, pp. 1400 - 1410, http://dx.doi.org/10.1038/s41375-018-0354-z
    Journal articles | 2019
    Wong M; Sun Y; Xi Z; Milazzo G; Poulos RC; Bartenhagen C; Bell JL; Mayoh C; Ho N; Tee AE; Chen X; Li Y; Ciaccio R; Liu PY; Jiang CC; Lan Q; Jayatilleke N; Cheung BB; Haber M; Norris MD; Zhang XD; Marshall GM; Wang JY; Hüttelmaier S; Fischer M; Wong JWH; Xu H; Perini G; Dong Q; George RE; Liu T, 2019, 'JMJD6 is a tumorigenic factor and therapeutic target in neuroblastoma', Nature Communications, vol. 10, pp. 3319, http://dx.doi.org/10.1038/s41467-019-11132-w
    Journal articles | 2017
    Sun Y; Atmadibrata B; Yu D; Wong M; Liu B; Ho N; Ling D; Tee AE; Wang J; Mungrue IN; Liu PY; Liu T, 2017, 'Upregulation of LYAR induces neuroblastoma cell proliferation and survival', Cell Death and Differentiation, vol. 24, pp. 1645 - 1654, http://dx.doi.org/10.1038/cdd.2017.98
    Journal articles | 2017
    Wong M; Tee AEL; Milazzo G; Bell JL; Poulos RC; Atmadibrata B; Sun Y; Jing D; Ho N; Ling D; Liu PY; Zhang XD; Hüttelmaier S; Wong JWH; Wang J; Polly P; Perini G; Scarlett CJ; Liu T, 2017, 'The histone methyltransferase DOT1L promotes neuroblastoma by regulating gene transcription', Cancer Research, vol. 77, pp. 2522 - 2533, http://dx.doi.org/10.1158/0008-5472.CAN-16-1663
    Journal articles | 2016
    Liu PY; Sokolowski N; Guo ST; Siddiqi F; Atmadibrata B; Telfer TJ; Sun Y; Zhang L; Yu D; Mccarroll J; Liu B; Yang RH; Guo XY; Tee AE; Itoh K; Wang J; Kavallaris M; Haber M; Norris MD; Cheung BB; Byrne JA; Ziegler DS; Marshall GM; Dinger ME; Codd R; Zhang XD; Liu T, 2016, 'The BET bromodomain inhibitor exerts the most potent synergistic anticancer effects with quinone-containing compounds and anti-microtubule drugs', Oncotarget, vol. 7, pp. 79217 - 79232, http://dx.doi.org/10.18632/oncotarget.12640
    Journal articles | 2016
    Lynch JR; Yi H; Casolari DA; Voli F; Gonzales-Aloy E; Fung TK; Liu B; Brown A; Liu T; Haber M; Norris MD; Lewis ID; So CWE; D'Andrea RJ; Wang JY, 2016, 'Gaq signaling is required for the maintenance of MLL-AF9-induced acute myeloid leukemia', Leukemia, vol. 30, pp. 1745 - 1748, http://dx.doi.org/10.1038/leu.2016.24
    Journal articles | 2014
    Dietrich PA; Yang C; Leung HHL; Lynch JR; Gonzales E; Liu B; Haber M; Norris MD; Wang J; Wang JY, 2014, 'GPR84 sustains aberrant β-catenin signaling in leukemic stem cells for maintenance of MLL leukemogenesis', Blood, vol. 124, pp. 3284 - 3294, http://dx.doi.org/10.1182/blood-2013-10-532523
    Journal articles | 2013
    Dietrich PA; Norris MD; Wang JY, 2013, 'GPR84, a Proinflammatory Receptor, Sustains Wnt/β-Catenin Signaling In Leukemic Stem Cells For Maintenance Of MLL-AF9-Induced Leukemogenesis', Blood, vol. 122, pp. 3781 - 3781, http://dx.doi.org/10.1182/blood.v122.21.3781.3781
    Journal articles | 2012
    Wang JY; Sprod O; Haber M; Norris MD, 2012, 'Epigenetic Elimination of Mixed-Lineage Leukemia Leukemic Stem Cells by a Potent Small Molecule PRC2 Inhibitor.', Blood, vol. 120, pp. 2456 - 2456, http://dx.doi.org/10.1182/blood.v120.21.2456.2456
  • Conference Papers | 2016
    Gonzales-Aloy E; Norris MD; Wang JY, 2016, 'Abstract 1917: Suppression of miR-101a contributes to leukemogenesis by regulating epigenetic and pro-survival pathways in MLL AML stem cells', in Cancer Research, American Association for Cancer Research (AACR), pp. 1917 - 1917, presented at Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA, http://dx.doi.org/10.1158/1538-7445.am2016-1917
    Conference Papers | 2014
    Dietrich PA; Norris MD; Wang JY, 2014, 'GNA13, a Novel Component of the GPR84/Beta-Catenin Signaling Axis in AML Stem Cells, Regulates the Maintenance of MLLAF9 Leukemogenesis', in BLOOD, AMER SOC HEMATOLOGY, https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000349242705068&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=891bb5ab6ba270e68a29b250adbe88d1