Prof Neil Watkins

Petre Chair in Cancer Biology, Lab Head - Cancer Developmental Biology

After completing medical school, physician training and a PhD in Perth Western Australia, Dr Watkins moved to the Johns Hopkins Kimmel Cancer Centre in Baltimore MD, reaching the rank of Associate Professor of Oncology.  During his postdoctoral training, he was supervised by Dr Steve Baylin (Professor of Oncology, Assistant Director of the Sidney Kimmel Cancer Centre) and Dr Phil Beachy (Professor of Molecular Biology and Genetics and Howard Hughes Medical Investigator).  Both are world-renowned in the fields of cancer epigenetics and developmental biology, respectively. 

His work focused on the role of aberrant developmental pathways in cancer and how they might be pharmacologically exploited therapeutically.  These studies have led to several extremely high impact publications, funding from internationally competitive research grants, multiple research awards and the development of a rapid translational pipeline, resulting in the delivery of these new therapeutic approaches the clinic.

His PhD thesis was supported by an NHRMC scholarship, and the first two years of his postdoctoral fellowship by a NHMRC CJ Martin Fellowship.  While on the faculty at Johns Hopkins, he successfully obtained large-scale extramural funding as a principal investigator, including several NIH grants. His work was also recognised by several highly prestigious awards, including the National Cancer Institute Career Development Award, the General Motors Award for Cancer Research, and the Children’s Brain Tumour Foundation House of Hope Award.

Since his return to Australia in 2009, Dr Watkins has secured major NHMRC funding, including a Senior Research Fellowship, and large scale program funding from the Victorian Cancer Agency (VCA). Within 5 years, he has established a basic and translational research laboratory of 8 outstanding young scientists, established key collaborations within Australia, and has developed a nationally recognised mouse cancer genetics program. In addition, he has played key leadership roles in Monash University’s strategic plan for cancer research, the formation of the Monash Comprehensive Cancer Consortium, and more recently, as an advisor to the Victorian Minister for Health on the Victorian Cancer Agency Council.

Research Interests

Cancer
Developmental Biology
Epigenetics
Mouse Models of Cancer
Lung Cancer
Cancers of Childhood

Awards and Honours

2010 - Monash Medical Student Outstanding Supervisor Award, Monash University
2009 - NHMRC Senior Research Fellowship
2005 - Research Fellowship, Sidney Kimmel Cancer Research Foundation
2004 - National Cancer Institute Career Development Award
2003 - General Motors Scholars Award, Johns Hopkins University
2002 - NCI/SPORE Career Development Award, National Cancer Institute
1998 - NHMRC of Australia CJ Martin Fellowship, NHMRC
1997 - Thoracic Society of Australia and New Zealand Young Investigator Award

Education

1998 - PhD, University of Western Australia
1993 - FRACP, Royal Australasian College of Physicians, Australia
1987 - MBBS, University of Western Australia

Selected Publications

Lee WTY, Cain JE, Cuddihy A, Johnson J, Dickinson A, Yeung K-Y, Kimar B, Johns TG, Watkins DN, Spencer A, St John JC. Mitochondrial DNA plasticity is an essential inducer of tumorigenesis. Cell Death Discovery, 2016; 2:16016.

Rogers S, Fey D, McCloy RA, Parker BL, Mitchell NJ, Payne RJ, Daly RJ, James DE, Caldon CE, Watkins DN, Croucher DR, Burgess A. PP1 initiates the dephosphorylation of MASTL, triggering mitotic exit and bistability in human cells. J Cell Sci, 2016 Apr 1;129(7):1340-54.

Muscat A, Popovski D, Jayasekara S, Rossello F, Alamgeer M, Algar EM, Feguson M, Downie P, Watkins DN, Cain JE, Ashley DM. Low-dose histone deacetylase inhibitor treatment leads to tumour growth arrest and multi-lineage differentiation of malignant rhabdoid tumours. Clin Cancer Res, 2016 clincanres.2260.2015. [Epub ahead of print]

Deane JA, Ong YR, Cain JE, Jayesekara SW, Tiwari A, Carlone DL, Watkins DN, Breault DT, Gargett CE. The mouse endometrium contains epithelial, endothelial and leukocyte populations expressing the stem cell marker telomerase reverse transcriptase. Human Mol Reprod, 2016 Apr;22(4):272-84

Rogers R, McCloy RA, Parker BL, Chauduri V, Gayevskiy V, Hoffman NJ, Daly RJ, James DE, Watkins DN, Burgess A. Dataset from the global phosphoproteomic mapping of early mitotic exit in human cells. Data in Brief, 2015; Aug 24;5:45-52.

Lim Y, Gondek L, Wang Q, Ma H, Chang E, Huso DL, Foerster S, Marchionni L, McGovern K, Watkins DN, Peacock CD, Levis M, Smith BD, Merchant AA, Small D, Matsui W. Integration of Hedgehog and mutant FLT3 signaling in myeloid leukemia. Sci Transl Med, 2015; 7:291ra96. [Reviewed in “Research Watch”, Cancer Discov, 2015 Jun 18]

McCloy R, Parker BL, Rodgers S, Hoffman NJ, Ali N, Daly R, Watkins DN, James DE, Lorca T, Castro A, Burgess A. Global phosphoproteomic mapping of early mitotic exit in human cells identifies novel substrate dephosphorylation motifs. Mol Cell Proteomics, 2015; Aug;14(8):2194-2212. [Cover article]

Sadler AJ, Rossello FJ, Yu L, Deane JA, Yuan X, Wang D, Irving AT, Kaparakis-Liasokos M, Gantier MP, Ying H, Yim HCH, Hartland E, Notini AJ, de Boer S, White S, Mansell A, Liu J-P, Watkins DN, Gerondakis S, Williams BRG, Xu D. The BTB-ZF transcriptional regulator, PLZF, modifies chromatin to restrain inflammatory signaling programs. Proc Natl Acad Sci USA, 2015 Feb 3;112(5):1535-40.

Boolell V, Alamgeer A, Watkins DN, Ganju V. The Evolution of Therapies in Non-Small Cell Lung Cancer. Cancers, 2015; 7: 1815-1846.

Lim CB, Prele C, Baltic S, Arthur P, Creaney J, Watkins DN, Thompson PJ, Mutsaers SJ. Mitochondria-derived reactive oxygen species drive GANT61-induced mesothelioma cell apoptosis. Oncotarget, 2015 Jan 30;6(3):1519-30.

Cochrane C, Szczepny A, Watkins DN, Cain JE. Hedgehog Signaling in the Maintenance of Cancer Stem Cells. Cancers, 2015;7(3): 1554-85.

Lewin J, Cullinane C, Akhurst T, Waldeck K, Watkins DN, Rao A, Eu P, Mileshkin L, Hicks RJ. Peptide receptor chemoradionuclide therapy in small cell carcinoma: from bench to bedside. Eur J Nucl Med Mol Imaging. 2015 Jan;42(1):25-32.

Leong TL, Marini KD, Rossello FJ, Jayesekara SN, Russell PA, Prodanovic Z, Kumar B, Ganju V, Alamgeer M, Irving LB, Steinfort DP, Peacock CD, Cain JE, Szczepny A, Watkins DN. Genomic Characterisation of Small Cell Lung Cancer Patient-Derived Xenografts Generated from Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Specimens. PloS One, 2014; 9(9):e106862.

Wang DH, Tiwari A, Kim ME, Clemons NJ, Regmi NL, Hodges WA, Berman DM, Montgomery EA, Watkins DN, Zhang X, Zhang Q, Jie C, Spechler SJ, Souza RF. Hedgehog signaling regulates Foxa2 in esophageal embryogenesis and Barrett’s metaplasia. J Clin Invest, 2014; 2;124(9):3767-80

Van der Zwan YG, Rijlaarsdam MA, Rosello FJ, Notn AJ, de Boer S, Watkins DN, Gillis AJM, Dorssers LCJ, White SJ, Looijenga LHJ. Seminoma and embryonal carcinoma footprints identified by analysis of integrated genome-wide epigenetic and expression profiles of germ cell cancer cell lines. PLoS One, 2014 ;9(6):e98330.

Stirling RG, Evans SM, McLaughlin P, Senthuren M, Millar J, Gooi J, Irving L, Mitchell P, Haydon A, Ruben J, Conron M, Leong T, Watkins N, McNeil JJ. The Victorian Lung Cancer Registry Pilot: Improving the Quality of Lung Cancer Care Through the Use of a Disease Quality Registry. Lung. 2014 Oct;192(5):749-58. [Epub ahead of print]

Alamgeer M, Ganju V, Kumar B, Fox J, Hart S, White M, Harris M, Stuckey J, Prodanovic Z, Schneider M, Watkins DN. Changes in ALDEHYDE DEHYDROGENASE-1 (ALDH1) expression during neoadjuvant chemotherapy predict outcome in locally advanced breast cancer. Breast Cancer Res, 2014; 16:R44.

Grzelak CA, MartelottoLG, Sigglekow ND, Patkunanathan B, Ajami K, Calabro SR, Dwyer BJ, Tirnitz-Parker NE, Watkins DN, Warner FJ, Shackel NA, McCaughan GW. The Intrahepatic Signaling Niche of Hedgehog is Defined by Primary Cilia-Positive Cells During Chronic Liver Injury. J Hepatol, 2014; 60(1):143-51.

Rossello F, Tothill R, Britt K, Marini K, Falzon J, Thomas D, Peacock C, Marchionni L, Li J, Bennett S, Tantoso E, Brown T, Chan P, Martelotto L, Watkins DN. Next-Generation Sequence Analysis of Cancer Xenografts. PLoS One, 2013; 8(9):e74432.

Alamgeer M, Ganju V, Szczepny A, Russell PA, Prodanovic Z, Kumar B, Wainer Z, Brown T, Schneider-Kosky M, Conron M, Wright G, Watkins DN. The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early-stage non-small cell lung cancer. Thorax, 2013; 68(12):1095-104.

Park KS, Martelotto LG, Peifer M, Sos ML, Karnezis AN, Mahjoub MR, Bernard K, Conklin J, Szczepny A, Yuan J, Guo R, Ospina B, Falzon J, Bennett S, Brown TL, Markovic A, Devereux WL, Ocasio CR, Chen JK, Stearns T, Dorsch M, Buonamici S, Watkins DN, Peacock CD, Sage J.  A critical requirement for Hedgehog signalling in small cell lung cancer.  Nat Med, 2011; 17:1504-1509.

O'Toole SA, Machalek DA, Shearer RF, Millar EKA, Nair R, Schofield P, McLeod D, Cooper CL, McNeil CM, McFarland A, Nguyen A, Ormandy CJ, Qiu MR, Rabinovich B, Martelotto LG, Vu D, Hannigan GE, Musgrove EA, Christ D, Sutherland RL, Watkins DN*, Swarbrick A*. Hedgehog Overexpression Is Associated with Stromal Interactions and Predicts for Poor Outcome in Breast Cancer. Cancer Res, 2011; 71:4002-4014. *Co-corresponding author.

Wang DH, Clemons NJ, Miyashita T, Dupuy, AJ, Zhang, W, Szczepny A, Corcoran-Schwartz IM, Wilburn DL, Montgomery EA, Wang JS, Jenkins NA, Copeland N, Harmon JW, Phillips WA, Watkins DN.  Aberrant Epithelial-Mesenchymal Hedgehog Signalling Characterizes Barrett's Metaplasia.  Gastroenterology, 2010; 138:1810–1822.

Zhang W, Zeng X, Briggs KJ, Beaty R, Simons B, Yen R-W, Tyler MA, Tsai H-C, Ye Y, Gesell GS, Herman JG, Baylin SB, Watkins DN.  A potential tumor suppressor role for Hic1 in breast cancer through transcriptional repression of ephrin-A1.  Oncogene, 2010; 29, 2467–2476.

Daniel VC, Marchionni L, Hierman JS, Rhodes JT, Devereux W, Rudin CM, Yung R, Parmigani G, Dorsch M, Peacock CD, Watkins DN.  A primary xenograft model of small cell lung cancer reveals irreversible changes in gene expression imposed by culture in-vitroCancer Res, 2009; 69(8):3364-73.

Briggs KJ, Corcoran-Schwartz IM, Zhang, W, Harcke T, Devereux WL, Baylin SB, Eberhart CG, Watkins DN.  Cooperation between the Hic1 and Ptch1 Tumor Suppressors in Medulloblastoma. Genes Dev, 2008; 22:770-785.                       

Peacock CD, Wang Q, Gesell GS, Corcoran-Schwartz IM, Jones E, Kim J, Devereux WL, Rhodes JT, Huff CA, Beachy PA, Watkins DN*, Matsui W*.  Hedgehog signalling maintains a tumor stem cell compartment in multiple myeloma.  Proc Natl Acad Sci USA, 2007; 104:4048-53. *Co-corresponding author with equal contribution.

Suzuki H, Watkins DN, Jair KW, Schuebel KE, Markowitz SD, Chen WD, Pretlow TP, Yang B, Akiyama Y, von Engeland M, Toyota M, Tokino T, Hinoda Y, Imai K, Herman JG and Baylin SB.  Epigenetic inactivation of SFRP genes allows constitutive WNT signalling in colorectal cancer.  Nat Genet, 2004; 36:417-422.

Berman DM, Karhadkar SS, Maitra A, Montes de Oca R, Gerstenblith MR, Briggs K, Parker AR, Shimada Y, Eshleman JR, Watkins DN, Beachy, PA.  Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours.  Nature, 2003; 425:846-851.

Watkins DN*, Berman DM, Burkholder SG, Wang B, Beachy PA, Baylin SB.  Hedgehog Signalling Within Airway Epithelial Progenitors and in Small Cell Lung Cancer.  Nature, 2003; 422:313-317.*Corresponding Author.

Chen WY, Zeng X, Carter MG, Morrell CN, Chiu Yen RW, Esteller M, Watkins DN, Herman JG, Mankowski JL, Baylin SB.  Heterozygous disruption of Hic1 predisposes mice to a gender-dependent spectrum of malignant tumors.  Nat Genet, 2003; 33:197-202.

Berman, DM, Karhadkar, SS, Hallahan, AR, Pritchard JI, Eberhart, CG, Watkins DN, Chen, JK, Cooper, MK, Taipale, J, Olson JM, Beachy PA.  Medulloblastoma Growth Inhibition by Hedgehog Pathway Blockade.  Science, 2002; 297:1559-1561.

Nakakura EK, Watkins DN, Schuebel KE, Srurianpong V, Borges MW, Nelkin BD, Ball DW.  Mammalian Scratch, a neural-specific Snail family transcriptional repressor.  Proc Natl Acad Sci USA, 2001; 98:4101-4015.

Prof Neil Watkins