Dr Lauren Watt
Postdoctoral Researcher
School of Biomedical Sciences and Pharmacy
Career Summary
Biography
Dr Watt started a Bachelor of Biomedical sciences as a second option to studying Medicine. Once begun she discovered a world of research and enjoyed progressing from Bachelor, to Honours (with University Medal) and through to a PhD program all at the University of Newcastle.
Honours project investigated the role of Protein phosphatase 2A (PP2A) in mast cells - with a focus on Asthma.
PhD studies transferred that knowledge of the Protein Phosphatase into a breast cancer setting, where she established a 3D cell culture of human breast ducts to investigate how mutations in PP2A affect the development of breast cancer characteristics. This work was generously supported by a Cancer institute of NSW Research Scholars Award.
At the completion of her PhD, family life took her away from the laboratory that she 'grew up in', and Associate Professor Nikki Verrills who had mentored her throughout.
However, her research expertise is not 'going to waste'. In 2021 as her children were growing, Dr Watt has returned to the Verrills laboratory as a part-time post-doctoral researcher. Though still no longer living in Newcastle, she maintains an online connection with the laboratory and is currently involved with data analysis, literature reviews, administration and networking for the group.
Dr Watt is thrilled to be able to dedicate time to both family life as well as research, by assisting the wonderful research being done in whatever ways are needed. She hopes to continue to build her skillsets in bioinformatics and graphic data analysis to present the findings of the Verrills lab team in a clear and informative way.
Qualifications
- Doctor of Philosophy, University of Newcastle
- Bachelor of Biomedical Sciences, University of Newcastle
- Bachelor of Biomedical Sciences (Hons), University of Newcastle
Keywords
- Breast Cancer
- Data Analysis
- Protein Phosphatase 2A
Fields of Research
Code | Description | Percentage |
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321101 | Cancer cell biology | 100 |
Professional Experience
UON Appointment
Title | Organisation / Department |
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Postdoctoral Researcher | University of Newcastle School of Biomedical Sciences and Pharmacy Australia |
Publications
For publications that are currently unpublished or in-press, details are shown in italics.
Journal article (3 outputs)
Year | Citation | Altmetrics | Link | ||||||||
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2017 |
Watt LF, Panicker N, Mannan A, Copeland B, Kahl RGS, Dun MD, et al., 'Functional importance of PP2A regulatory subunit loss in breast cancer', Breast Cancer Research and Treatment, 166 117-131 (2017) [C1] Purpose: Protein phosphatase 2A (PP2A) is a family of serine/threonine phosphatases that regulate multiple cellular signalling pathways involved in proliferation, survival and apo... [more] Purpose: Protein phosphatase 2A (PP2A) is a family of serine/threonine phosphatases that regulate multiple cellular signalling pathways involved in proliferation, survival and apoptosis. PP2A inhibition occurs in many cancers and is considered a tumour suppressor. Deletion/downregulation of PP2A genes has been observed in breast tumours, but the functional role of PP2A subunit loss in breast cancer has not been investigated. Methods: PP2A subunit expression was examined by immunohistochemistry in human breast tumours, and by qPCR and immunoblotting in breast cancer cell lines. PP2A subunits were inhibited by shRNA, and mutant PP2A genes overexpressed, in MCF10A and MCF7 cells, and growth and signalling in standard and three-dimensional cultures were assessed. Results: Expression of PP2A-Aa, PP2A-Ba and PP2A-B'a subunits was significantly lower in primary human breast tumours and lymph node metastases, compared to normal mammary tissue. PP2A-Aa and the regulatory subunits PP2A-Ba, -Bd and -B'¿ were also reduced in breast cancer cell lines compared to normal mammary epithelial cells. Functionally, shRNA-mediated knockdown of PP2A-Ba, -B'a and -B'¿, but not PP2A-Aa, induced hyper-proliferation and large multilobular acini in MCF10A 3D cultures, characterised by activation of ERK. Expression of a breast cancer-associated PP2A-A mutant, PP2A-Aa-E64G, which inhibits binding of regulatory subunits to the PP2A core, induced a similar hyper-proliferative phenotype. Knockdown of PP2A-Ba also induced hyper-proliferation in MCF7 breast cancer cells. Conclusion: These results suggest that loss of specific PP2A regulatory subunits is functionally important in breast tumourigenesis, and support strategies to enhance PP2A activity as a therapeutic approach in breast cancer.
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Nova | |||||||||
2014 |
Hoffman A, Carpenter H, Kahl R, Watt LF, Dickson PW, Rostas JAP, et al., 'Dephosphorylation of CaMKII at T253 controls the metaphase-anaphase transition', Cellular Signalling, 26 748-756 (2014) [C1] Calcium/calmodulin-stimulated protein kinase II (CaMKII) is a multi-functional serine/threonine protein kinase that controls a range of cellular functions, including proliferation... [more] Calcium/calmodulin-stimulated protein kinase II (CaMKII) is a multi-functional serine/threonine protein kinase that controls a range of cellular functions, including proliferation. The biological properties of CaMKII are regulated by multi-site phosphorylation and targeting via interactions with specific proteins. To investigate the role specific CaMKII phosphorylation sites play in controlling cell proliferation and cell cycle progression, we examined phosphorylation of CaMKII at two sites (T253 and T286) at various stages of the cell cycle, and also examined the effects of overexpression of wild-type (WT), T286D phosphomimic, T253D phosphomimic and T253V phosphonull forms of CaMKIIa in MDA-MB-231 breast cancer and SHSY5Y neuroblastoma cells on cellular proliferation and cell cycle progression. We demonstrate herein that whilst there is no change in total CaMKII expression or T286 phosphorylation throughout the cell cycle, a marked dephosphorylation of CaMKII at T253 occurs during the G2 and/or M phases. Additionally, we show by molecular inhibition, as well as pharmacological activation, that protein phosphatase 2A (PP2A) is the phosphatase responsible for this dephosphorylation. Furthermore, we show that inducible overexpression of WT, T286D and T253V forms of CaMKIIa in MDA-MB-231 and SHSY5Y cells increases cellular proliferation, with no alteration in cell cycle profiles. By contrast, overexpression of a T253D phosphomimic form of CaMKIIa significantly decreases proliferation, and cells accumulate in mitosis, specifically in metaphase. Taken together, these results strongly suggest that the dephosphorylation of CaMKII at T253 is involved in controlling the cell cycle, specifically the metaphase-anaphase transition. © 2014 Elsevier Inc.
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Nova | |||||||||
2010 |
Kranias G, Watt L, Carpenter HC, Holst J, Ludowyke R, Strack S, et al., 'Protein phosphatase 2A carboxymethylation and regulatory B subunits differentially regulate mast cell degranulation', Cellular Signalling, 22 1882-1890 (2010) [C1]
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Nova |
Conference (3 outputs)
Year | Citation | Altmetrics | Link | ||
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2015 |
Watt LF, Panicker N, Copeland B, Kahl RGS, Dun MD, Young B, et al., 'PP2A a novel biomarker and therapeutic target for poor outcome breast cancer', Proceedings of the Lowy Cancer Conference, Sydney (2015) [E3]
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2015 |
Mannan A, Panicker N, Watt L, Kahl R, Dun M, Skelding K, Verrills N, 'ROLE OF REDUCED PROTEIN PHOSPHATASE 2A SUBUNIT, B55A, EXPRESSION IN LUMINAL B BREAST CANCER CELL LINE DNA DAMAGE REPAIR PATHWAY', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
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2015 |
Panicker N, Watt L, Kahl R, Dun M, Greer P, Skelding K, Verrills N, 'REDUCED EXPRESSION OF PROTEIN PHOSPHATASE 2A SUBUNIT, B55A, IN BREAST CANCER DNA DAMAGE REPAIR PATHWAYS', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
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Grants and Funding
Summary
Number of grants | 1 |
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Total funding | $75,000 |
Click on a grant title below to expand the full details for that specific grant.
20071 grants / $75,000
The role of serine/theonine protein phosphatases in breast cancer$75,000
Funding body: Cancer Institute NSW
Funding body | Cancer Institute NSW |
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Project Team | Doctor Lauren Watt |
Scheme | Research Scholars Award |
Role | Lead |
Funding Start | 2007 |
Funding Finish | 2009 |
GNo | G0186992 |
Type Of Funding | Contract - Aust Non Government |
Category | 3AFC |
UON | Y |
Research Projects
Verrills Laboratory 2012 -
Grants
A dual approach to activate a tumour suppressor for breast cancer therapy
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
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Project Team | Doctor Severine Roselli Dayas, Associate Professor Jonathan Morris, Associate Professor Nikki Verrills |
Scheme | Ideas Grants |
Targeting DNA-PK in acute myeloid leukaemia
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
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Project Team | Associate Professor Nikki Verrills, Associate Professor Anoop Enjeti |
Scheme | Ideas Grants |
Publications
Roberts KG, Smith AM, McDougall FK, Carpenter HC, Horan MP, Neviani P, et al., 'Essential requirement for PP2A inhibition by the oncogenic receptor c-KIT suggests PP2A reactivation as a strategy to treat c-KIT+ cancers', Cancer Research, 70 5438-5447 (2010) [C1]
Smith AM, Dun MD, Lee EM, Harrison C, Kahl R, Flanagan H, et al., 'Activation of protein phosphatase 2A in FLT3+ acute myeloid leukemia cells enhances the cytotoxicity of FLT3 tyrosine kinase inhibitors', Oncotarget, 7 47465-47478 (2016) [C1]
Murray HC, Dun MD, Verrills NM, 'Harnessing the power of proteomics for identification of oncogenic, druggable signalling pathways in cancer', Expert Opinion on Drug Discovery, 12 431-447 (2017) [C1]
Watt LF, Panicker N, Mannan A, Copeland B, Kahl RGS, Dun MD, et al., 'Functional importance of PP2A regulatory subunit loss in breast cancer', Breast Cancer Research and Treatment, 166 117-131 (2017) [C1]
Dun MD, Mannan A, Rigby CJ, Butler S, Toop HD, Beck D, et al., 'Shwachman Bodian Diamond syndrome (SBDS) protein is a direct inhibitor of protein phosphatase 2A (PP2A) activity and overexpressed in acute myeloid leukaemia', Leukemia, 34 3393-3397 (2020) [C1]
Panicker N, Coutman M, Lawlor-O'Neill C, Kahl RGS, Roselli S, Verrills NM, 'Ppp2r2aKnockout Mice Reveal That Protein Phosphatase 2A Regulatory Subunit, PP2A-B55 alpha, Is an Essential Regulator of Neuronal and Epidermal Embryonic Development', FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 8 (2020) [C1]
Murray HC, Enjeti AK, Kahl RGS, Flanagan HM, Sillar J, Skerrett-Byrne DA, et al., 'Quantitative phosphoproteomics uncovers synergy between DNA-PK and FLT3 inhibitors in acute myeloid leukaemia', LEUKEMIA, 35 1782-1787 (2021)
Students
Program | Research Title |
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PhD College of Health, Medicine and Wellbeing |
Multiomic Characterisation of Cellular Signalling Regulated by PP2A-B55a in Breast Cancer and Development |
Collaborators
Name | Organisation |
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Doctor Heather Constance Murray | University of Newcastle |
Doctor Nikita Panicker | University of Newcastle |
Miss Charley Louise Lawlor-O'Neill | University of Newcastle |
Doctor Lauren Frances Watt | University of Newcastle |
Miss Kasey Erin Miller | University of Newcastle |
Mr Joshua Stephen Sidney Brzozowski | University of Newcastle |
Doctor Yanfang Chen | University of Newcastle |
Doctor Severine Roselli Melanie Dayas | University of Newcastle |
Edit
Dr Lauren Watt
Position
Postdoctoral Researcher
School of Biomedical Sciences and Pharmacy
College of Health, Medicine and Wellbeing