Dr Ting La

Dr Ting La

Postdoctoral Researcher

School of Biomedical Sciences and Pharmacy

Career Summary

Biography

Dr Ting La has been working on cancer cell biology with a focused aim to understand mechanisms of regulation of melanoma cell quiescence since the commencement of her PhD candidature in 2016. Her work has resulted in several publications. Ting La obtained her PhD in Medical Biochemistry from the University of Newcastle in 2019. Her past work not only enabled her to be trained systemically with techniques and skills necessary for cancer research, but also made her realize the complexity of cancer cells, especially the metabolic switching between glycolysis and oxidative phosphorylation in cancer cells under treatment. As a logical extension, she continues investigating roles of cancer cell metabolism in cancer development, progression and resistance to treatment.

Ting La is currently a postdoctoral researcher at the University of Newcastle. She is employed through a NHMRC project grant held by Prof. Xu Dong Zhang. During this time, she contributes to strong training, supervision, and mentoring programs of Prof.  Zhang’s Lab. She is also assisting with supervision of RHD students and visiting academics.


Qualifications

  • Doctor of Philosophy, University of Newcastle
  • Masters of Science, Shangai Jiao Tong University - China

Keywords

  • Cancer biology
  • Genome editing

Languages

  • Chinese, nec (Mother)
  • English (Fluent)

Fields of Research

Code Description Percentage
111201 Cancer Cell Biology 60
060104 Cell Metabolism 20
060199 Biochemistry and Cell Biology not elsewhere classified 20

Professional Experience

UON Appointment

Title Organisation / Department
Postdoctoral Researcher University of Newcastle
School of Biomedical Sciences and Pharmacy
Australia
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (12 outputs)

Year Citation Altmetrics Link
2020 Feng YC, Liu XY, Teng L, Ji Q, Wu Y, Li JM, et al., 'c-Myc inactivation of p53 through the pan-cancer lncRNA MILIP drives cancer pathogenesis.', Nat Commun, 11 4980 (2020) [C1]
DOI 10.1038/s41467-020-18735-8
Co-authors Xu Zhang, Rick Thorne, Lei Jin, Muhammad Jamaluddin, Rodney Scott
2020 La T, Jin L, Liu XY, Song ZH, Farrelly M, Feng YC, et al., 'Cylindromatosis is required for survival of a subset of melanoma cells.', Oncology Research, 28 385-398 (2020) [C1]
DOI 10.3727/096504020x15861709922491
Co-authors Xu Zhang, Yuanyuan Zhang, Lei Jin, Rick Thorne
2019 Zhang W, Guo T, Chen K, La T, Bastians PA, Cao C, 'The microstructure investigation of plant architecture with X-ray microscopy (2019)
DOI 10.1101/729533
2019 Yari H, Jin L, Teng L, Wang Y, Wu Y, Liu GZ, et al., 'LncRNA REG1CP promotes tumorigenesis through an enhancer complex to recruit FANCJ helicase for REG3A transcription', NATURE COMMUNICATIONS, 10 (2019) [C1]
DOI 10.1038/s41467-019-13313-z
Citations Scopus - 4Web of Science - 1
Co-authors Yuanyuan Zhang, Rick Thorne, Rodney Scott, Xu Zhang, Lei Jin
2018 La T, Liu GZ, Farrelly M, Cole N, Feng YC, Zhang YY, et al., 'A p53-responsive miRNA network promotes cancer cell quiescence', Cancer Research, 78 6666-6679 (2018) [C1]

© 2018 American Association for Cancer Research. Cancer cells in quiescence (G0 phase) are resistant to death, and re-entry of quiescent cancer cells into the cell-cycle plays an ... [more]

© 2018 American Association for Cancer Research. Cancer cells in quiescence (G0 phase) are resistant to death, and re-entry of quiescent cancer cells into the cell-cycle plays an important role in cancer recurrence. Here we show that two p53-responsive miRNAs utilize distinct but complementary mechanisms to promote cancer cell quiescence by facilitating stabilization of p27. Purified quiescent B16 mouse melanoma cells expressed higher levels of miRNA-27b-3p and miRNA-455-3p relative to their proliferating counterparts. Induction of quiescence resulted in increased levels of these miRNAs in diverse types of human cancer cell lines. Inhibition of miRNA-27b-3p or miRNA-455-3p reduced, whereas its overexpression increased, the proportion of quiescent cells in the population, indicating that these miRNAs promote cancer cell quiescence. Accordingly, cancer xenografts bearing miRNA-27b-3p or miRNA-455-3p mimics were retarded in growth. miRNA-27b-3p targeted cyclin-dependent kinase regulatory subunit 1 (CKS1B), leading to reduction in p27 polyubiquitination mediated by S-phase kinase-associated protein 2 (Skp2). miRNA-455-3p targeted CDK2-associated cullin domain 1 (CAC1), which enhanced CDK2-mediated phosphorylation of p27 necessary for its polyubiquitination. Of note, the gene encoding miRNA-27b-3p was embedded in the intron of the chromosome 9 open reading frame 3 gene that was transcriptionally activated by p53. Similarly, the host gene of miRNA-455-3p, collagen alpha-1 (XXVII) chain, was also a p53 transcriptional target. Collectively, our results identify miRNA-27b-3p and miRNA-455-3p as important regulators of cancer cell quiescence in response to p53 and suggest that manipulating miRNA-27b-3p and miRNA-455-3p may constitute novel therapeutic avenues for improving outcomes of cancer treatment. Significance: Two novel p53-responsive microRNAs whose distinct mechanisms of action both stabilize p27 to promote cell quiescence and may serve as therapeutic avenues for improving outcomes of cancer treatment.

DOI 10.1158/0008-5472.CAN-18-1886
Citations Scopus - 7Web of Science - 5
Co-authors Rick Thorne, Yuanyuan Zhang, Lei Jin, Xu Zhang
2017 Wang JY, Liu GZ, Wilmott JS, La T, Feng YC, Yari H, et al., 'Skp2-mediated stabilization of MTH1 promotes survival of melanoma cells upon oxidative stress', Cancer Research, 77 6226-6239 (2017) [C1]

©2017 AACR. MTH1 helps prevent misincorporation of ROS-damaged dNTPs into genomic DNA; however, there is little understanding of how MTH1 itself is regulated. Here, we report that... [more]

©2017 AACR. MTH1 helps prevent misincorporation of ROS-damaged dNTPs into genomic DNA; however, there is little understanding of how MTH1 itself is regulated. Here, we report that MTH1 is regulated by polyubiquitination mediated by the E3 ligase Skp2. In melanoma cells, MTH1 was upregulated commonly mainly due to its improved stability caused by K63-linked polyubiquitination. Although Skp2 along with other components of the Skp1-Cullin-F-box (SCF) ubiquitin ligase complex was physically associated with MTH1, blocking the SCF function ablated MTH1 ubiquitination and expression. Conversely, overexpressing Skp2-elevated levels of MTH1 associated with an increase in its K63-linked ubiquitination. In melanoma cell lines and patient specimens, we observed a positive correlation of Skp2 and MTH1 expression. Mechanistic investigations showed that Skp2 limited DNA damage and apoptosis triggered by oxidative stress and that MAPK upregulated Skp2 and MTH1 to render cells more resistant to such stress. Collectively, our findings identify Skp2-mediated K63-linked polyubiquitination as a critical regulatory mechanism responsible for MTH1 upregulation in melanoma, with potential implications to target the MAPK/Skp2/MTH1 pathway to improve its treatment.

DOI 10.1158/0008-5472.CAN-17-1965
Citations Scopus - 17Web of Science - 14
Co-authors Rick Thorne, Xu Zhang, Lei Jin
2017 Liu F, Jiang CC, Yan XG, Tseng H-Y, Wang CY, Zhang YY, et al., 'BRAF/MEK inhibitors promote CD47 expression that is reversible by ERK inhibition in melanoma.', Oncotarget, 8 69477-69492 (2017) [C1]
DOI 10.18632/oncotarget.17704
Co-authors Lei Jin, Chenchen Jiang, Rick Thorne, Yuanyuan Zhang
2017 Liu F, Jiang CC, Yan XG, Tseng H-Y, Wang CY, Zhang YY, et al., 'BRAF/MEK inhibitors promote CD47 expression that is reversible by ERK inhibition in melanoma.', Oncotarget, 8 69477-69492 (2017) [C1]
DOI 10.18632/oncotarget.17704
Citations Scopus - 8Web of Science - 8
Co-authors Yuanyuan Zhang, Xu Zhang, Rick Thorne, Chenchen Jiang, Lei Jin
2016 Zhang F, Wu L, Qian J, Qu B, Xia S, La T, et al., 'Identification of the long noncoding RNA NEAT1 as a novel inflammatory regulator acting through MAPK pathway in human lupus', JOURNAL OF AUTOIMMUNITY, 75 96-104 (2016)
DOI 10.1016/j.jaut.2016.07.012
Citations Web of Science - 102
2016 Sun Z-C, Ge J-L, Guo B, Guo J, Hao M, Wu Y-C, et al., 'Extremely Low Frequency Electromagnetic Fields Facilitate Vesicle Endocytosis by Increasing Presynaptic Calcium Channel Expression at a Central Synapse', SCIENTIFIC REPORTS, 6 (2016)
DOI 10.1038/srep21774
Citations Web of Science - 23
2016 Wang JY, Jin L, Yan XG, Sherwin S, Farrelly M, Zhang YY, et al., 'Reactive Oxygen Species Dictate the Apoptotic Response of Melanoma Cells to TH588', Journal of Investigative Dermatology, 136 2277-2286 (2016) [C1]

© 2016 The Authors The effect of MTH1 inhibition on cancer cell survival has been elusive. Here we report that although silencing of MTH1 does not affect survival of melanoma cell... [more]

© 2016 The Authors The effect of MTH1 inhibition on cancer cell survival has been elusive. Here we report that although silencing of MTH1 does not affect survival of melanoma cells, TH588, one of the first-in-class MTH1 inhibitors, kills melanoma cells through apoptosis independently of its inhibitory effect on MTH1. Induction of apoptosis by TH588 was not alleviated by MTH1 overexpression or introduction of the bacterial homolog of MTH1 that has 8-oxodGTPase activity but cannot be inhibited by TH588, indicating that MTH1 inhibition is not the cause of TH588-induced killing of melanoma cells. Although knockdown of MTH1 did not impinge on the viability of melanoma cells, it rendered melanoma cells sensitive to apoptosis induced by the oxidative stress inducer elesclomol. Of note, treatment with elesclomol also enhanced TH588-induced apoptosis, whereas a reactive oxygen species scavenger or an antioxidant attenuated the apoptosis triggered by TH588. Indeed, the sensitivity of melanoma cells to TH588 was correlated with endogenous levels of reactive oxygen species. Collectively, these results indicate that the cytotoxicity of TH588 toward melanoma cells is not associated with its inhibitory effect on MTH1, although it is mediated by cellular production of ROS.

DOI 10.1016/j.jid.2016.06.625
Citations Scopus - 20Web of Science - 18
Co-authors Chenchen Jiang, Lei Jin, Xu Zhang, Yuanyuan Zhang
2016 Wang CY, Guo ST, Wang JY, Yan XG, Farrelly M, Zhang YY, et al., 'Reactivation of ERK and Akt confers resistance of mutant BRAF colon cancer cells to the HSP90 inhibitor AUY922', Oncotarget, 7 49597-49610 (2016) [C1]

Oncogenic mutations of BRAF occur in approximately 10% of colon cancers and are associated with their resistance to clinically available therapeutic drugs and poor prognosis of th... [more]

Oncogenic mutations of BRAF occur in approximately 10% of colon cancers and are associated with their resistance to clinically available therapeutic drugs and poor prognosis of the patients. Here we report that colon cancer cells with mutant BRAF are also resistant to the heat shock protein 90 (HSP90) inhibitor AUY922, and that this is caused by rebound activation of ERK and Akt. Although AUY922 triggered rapid reduction in ERK and Akt activation in both wild-type and mutant BRAF colon cancer cells, activation of ERK and Akt rebounded shortly in the latter leading to resistance of the cells to AUY922-induced apoptosis. Reactivation of ERK was associated with the persistent expression of mutant BRAF, which, despite being a client of HSP90, was only partially degraded by AUY922, whereas reactivation of Akt was related to the activity of the HSP90 co-chaperone, cell division cycle 37 (CDC37), in that knockdown of CDC37 inhibited Akt reactivation in mutant colon cancer cells treated with AUY922. In support, as a HSP90 client protein, Akt was only diminished by AUY922 in wild-type but not mutant BRAF colon cancer cells. Collectively, these results reveal that reactivation of ERK and Akt associated respectively with the activity of mutant BRAF and CDC37 renders mutant BRAF colon cancer cells resistant to AUY922, with implications of co-targeting mutant BRAF and/or CDC37 and HSP90 in the treatment of mutant BRAF colon cancers.

DOI 10.18632/oncotarget.10414
Citations Scopus - 9Web of Science - 8
Co-authors Chenchen Jiang, Lei Jin, Xu Zhang, Yuanyuan Zhang
Show 9 more journal articles

Conference (12 outputs)

Year Citation Altmetrics Link
2018 La T, Farrelly M, Yan XG, Yari H, Zhang Y, Feng Y, et al., 'A genomic editing approach for purification of viable quiescent cancer cells', CANCER RESEARCH, Chicago, IL (2018)
DOI 10.1158/1538-7445.AM2018-52
Co-authors Lei Jin, Yuanyuan Zhang, Xu Zhang
2018 Zhang YY, Yan XG, Farrelly M, Yari H, Feng Y, La T, et al., 'Long noncoding RNA OVAAL promotes melanoma cell proliferation through translational suppression of p27', CANCER RESEARCH, Chicago, IL (2018)
DOI 10.1158/1538-7445.AM2018-2451
Co-authors Lei Jin, Xu Zhang
2017 Wang CY, Guo ST, Wang JY, Yan XG, Farrelly M, Zhang YY, et al., 'Inhibition of hsp90 by auy922 preferentially kills mutant KRAS colon cancer cells by activating Bim through ER stress', CANCER RESEARCH, Washington, DC (2017)
DOI 10.1158/1538-7445.AM2017-3066
Co-authors Chenchen Jiang, Lei Jin, Xu Zhang
2017 Jin L, Tabatabaeehatambakhsh H, Jiang CC, Yan XG, Wang JY, Zhang YY, et al., 'ACTN4 stabilises RIPK1 to function as an oncogenic driver in melanoma', CANCER RESEARCH, Washington, DC (2017)
DOI 10.1158/1538-7445.AM2017-4462
Co-authors Xu Zhang, Chenchen Jiang, Lei Jin
2016 Jin L, Tabatabaee H, Yan XG, Wang JY, Zhang YY, Yari H, et al., 'A MICROFILAMENT PROTEIN AS A MASTER SWITCH AT THE INTERSECTION OF SURVIVAL SIGNALING PATHWAYS IN MELANOMA', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
Co-authors Chenchen Jiang, Xu Zhang, Lei Jin
2016 Zhang YY, Wang JY, Wang CY, Guo ST, Yan XG, Farrelly M, et al., 'APOPTOSIS-REGULATING LONG NONCODING RNAS IN MELANOMA', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
Citations Web of Science - 1
Co-authors Chenchen Jiang, Xu Zhang
2016 Wang YF, Liu F, Ji GY, Sherwin S, McFarlane J, Tseng H-Y, et al., 'IDENTIFICATION OF A NOVEL TRANSCRIPTION FACTOR COMPLEX IN CLASS I HDACS-MEDIATED UPREGULATION OF PD-L1 IN CANCER CELLS', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
Co-authors Lei Jin, Chenchen Jiang, Xu Zhang
2016 La T, Farrelly M, Wang JY, Wang CY, Yan XG, Zhang YY, et al., 'TOWARDS TARGETING QUIESCENT MELANOMA CELLS', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
Co-authors Lei Jin, Chenchen Jiang, Xu Zhang
2016 Lei F, Jin L, Yan XG, Liu F, Wang JY, Wang CY, et al., 'RIPK1 PROMOTES MELANOMA CELL SURVIVAL UPON MAPK INHIBITION', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
Co-authors Chenchen Jiang, Xu Zhang, Lei Jin
2016 Wang CY, Guo ST, Wang JY, Yan XG, Farrelly M, Zhang YY, et al., 'REACTIVATION OF ERK AND AKT CONFERS RESISTANCE OF MUTANT BRAF COLON CANCER CELLS TO THE HSP90 INHIBITOR AUY922', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
Co-authors Lei Jin, Chenchen Jiang, Xu Zhang, Yuanyuan Zhang
2016 Wang JY, Jin L, Yan XG, Sherwin S, Farrelly M, Zhang YY, et al., 'REACTIVE OXYGEN SPECIES DICTATE THE APOPTOTIC RESPONSE OF MELANOMA CELLS TO TH588', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
Co-authors Xu Zhang, Chenchen Jiang, Lei Jin
2016 Yari H, Jin L, Wang JY, Wang CY, Liu F, Zhang YY, et al., 'AN ONCOGENIC LONG NONCODING RNA IN HUMAN COLON CANCER', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2016)
Co-authors Xu Zhang, Chenchen Jiang, Lei Jin
Show 9 more conferences
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Grants and Funding

Summary

Number of grants 1
Total funding $30,000

Click on a grant title below to expand the full details for that specific grant.


20201 grants / $30,000

A CRISPR dropout screen to identify therapeutic targets for killing of quiescent melanoma cells$30,000

Funding body: HCRA Hunter Cancer Research Alliance

Funding body HCRA Hunter Cancer Research Alliance
Project Team

Ting La, Anoop Enjeti, Xu Dong Zhang,Lei Jin

Scheme Research Project
Role Lead
Funding Start 2020
Funding Finish 2021
GNo
Type Of Funding Internal
Category INTE
UON N
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Dr Ting La

Position

Postdoctoral Researcher
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Contact Details

Email ting.la@newcastle.edu.au
Phone (02) 4921 7970
Mobile 0404240683

Office

Room LSB2-05
Building Life Sciences Building
Location Callaghan
University Drive
Callaghan, NSW 2308
Australia
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