Prof Neil Watkins - Researcher Profile

Prof Neil Watkins

Address

Monash Institute of Medical Research
Centre for Cancer Research

Contact Details

Tel: +61 3 990 24765

Email: neil.watkins@monash.edu


Biography

An unlikely pairing in cancer research

Professor Neil Watkins says lung cancer and paediatric brain tumours may seem different from a research perspective, but they actually share vital biological characteristics.  Neil is interested in pathways that regulate the formation of organs from stem cells, and how these relate to cancer.  His research focuses on the medulloblastoma brain tumour and small-cell lung cancer.

While lung cancer is not as common as breast or prostate cancer, its 15 per cent survival rate makes it the most common cause of cancer-related death in Australia.  The medulloblastoma tumour, which mainly affects children, is similarly aggressive but has a much higher survival rate.  Despite the differences, Neil says biological similarities allow for exciting translational research.

“Small-cell lung cancer is the most virulent form of lung cancer,” Neil says.  “It comes from a small population of cells in the lining of the lung and shares characteristics with nerves and endocrine cells.  When tumours arise from those cells, they behave more like a primitive malignant brain tumour than lung cancer.  The closest thing to that tumour is medulloblastoma in kids.  Medulloblastoma is curable, while small-cell usually is not, but they share some common biology.  I stumbled on this when I was working on small-cell lung cancer and my colleagues were working on medulloblastoma.” 

Neil says one of the most important connections between lung cancer and the medulloblastoma brain tumour is their relationship with the hedgehog signalling pathway.  This gives cells information for embryo development, but it also plays a role in several types of cancer. 

“We think there are specific cancers and specific functions within cancers that depend heavily on that pathway.  We’re able to inhibit it with a specific compound, which comes from a plant.  Several companies have new synthetic compounds that target hedgehog signalling and they are in clinical trials.  Bristol-Myers Squibb is trialling one of their compounds at Monash Medical Centre,” he says.

Neil says paediatric cancers are ideal models for fundamental pathway research.

“Paediatric cancers are the most fundamentally important models we have for understanding how embryonic pathways - like hedgehog pathways - drive cancer.  They tend to come from a very pure population of stem-like cells in that organ.  They also have less genetic abnormalities than adult cancers and are driven by one single mutation.  If the cancer is totally driven by that one thing and you can target that thing, the cancer melts away.  That’s why they’re very important models.  We’re also in the final stages of starting a trial for bone tumours using a hedgehog inhibitor at Peter Mac [Callum Cancer Centre]”, he says.

Neil also played a key role in the formation of the Melbourne Comprehensive Cancer Consortium, which aims to bring together multi-disciplinary expertise and enhance Victoria’s Cancer Action Plan.

“We’re sort of a network encompassing our facility, The Alfred, Dandenong, Frankston and all the way out to Gippsland.  We have a large geographical group of clinicians and researchers that we’re trying to bring together. 

“Monash is very strong in lung cancer, paediatric cancer, colorectal cancer and leukaemia.  My role is to take those clinicians and researchers and connect them to the entire network to produce a better outcome for the institution and the patients.”

Keywords

Lung Cancer, Developmental Biology

Qualifications

POST DOC
Institution: Johns Hopkins University School of Medicine
Year awarded: 2003
DOCTOR OF PHILOSOPHY
Institution: University of WA
Year awarded: 1998
FRACP
Institution: Royal Australasian College of Physicians
Year awarded: 1993
BACHELOR OF MEDICINE/ BACHELOR OF SURGERY
Institution: University of WA
Year awarded: 1987

Publications

Journal Articles

Kelleher, F.C., Cain, J., Healy, J.M., Watkins, D.N., Thomas, D.M., 2012, Prevailing importance of the hedgehog signaling pathway and the potential for treatment advancement in sarcoma, Pharmacology and Therapeutics [P], vol 136, issue 2, Elsevier Inc., United States, pp. 153-168.

Clemons, N.J., Wang, D.H., Croagh, D., Tikoo, A., Fennell, C.M., Murone, C., Scott, A.M., Watkins, D.N., Phillips, W.A., 2012, Sox9 drives columnar differentiation of esophageal squamous epithelium: A possible role in the pathogenesis of Barrett's esophagus, American Journal Of Physiology-Gastrointestinal And Liver Physiology [P], vol 303, issue 12, American Physiological Society, United States, pp. G1335-G1346.

Park, K., Martelotto, L., Peifer, M., Sos, M., Karnezis, A., Mahjoub, M., Bernard, K., Conklin, J., Szczepny, A., Yuan, J., Guo, R., Ospina, B., Falzon, J., Bennett, S., Brown, T., Markovic, A., Devereux, W., Ocasio, C., Chen, J., Stearns, T., Thomas, R., Dorsch, M., Buonamici, S., Watkins, D., Peacock, C., Sage, J., 2011, A crucial requirement for Hedgehog signaling in small cell lung cancer, Nature Medicine [P], vol 17, issue 11, Nature Publishing Group, United States, pp. 1504-1508.

O'Toole, S., Machalek, D., Shearer, R., Millar, E., Nair, R., Schofield, P., Mcleod, D., Cooper, C., McNeil, C., McFarland, A., Nguyen, A., Ormandy, C., Qiu, M., Rabinovich, B., Martelotto, L., Vu, D., Hannigan, G., Musgrove, E., Christ, D., Sutherland, R., Watkins, D., Swarbrick, A., 2011, Hedgehog overexpression is associated with stromal interactions and predicts for poor outcome in breast cancer, Cancer Research [P], vol 71, issue 11, American Association for Cancer Research, United States, pp. 4002-4014.

Mohammad, H., Zhang, W., Prevas, H., Leadem, B., Zhang, M., Herman, J., Hooker, C., Watkins, D., Karim, B., Huso, D., Baylin, S., 2011, Loss of a single Hic1 allele accelerates polyp formation in Apc{delta716} mice, Oncogene [P], vol 30, issue 23, Nature Publishing Group, United Kingdom, pp. 2659-2669.

Marini, K., Payne, B., Watkins, D., Martelotto, L., 2011, Mechanisms of hedgehog signalling in cancer, Growth Factors [P], vol 29, issue 6, Informa Healthcare, UK, pp. 221-234.

Zhang, W., Zeng, X., Briggs, K.J., Beaty, R., Simons, B., Yen, R.C., Tyler, M.A., Tsai, H., Ye, Y., Gesell, G.S., Herman, J.G., Baylin, S.B., Watkins, D.N., 2010, A potential tumor suppressor role for Hic1 in breast cancer through transcriptional repression of ephrin-A1, Oncogene [P], vol 29, issue 17, Nature Publishing Group, UK, pp. 2467-2476.

Wang, D.H., Clemons, N.J., Miyashita, T., Dupuy, A.J., Zhang, W., Szczepny, A., Corcoran-Schwartz, I.M., WIlburn, D.L., Montgomery, E.A., Wang, J.S., Jenkins, N.A., Copeland, N.A., Harmon, J.W., Phillips, W.A., Watkins, D.N., 2010, Aberrant epithelial-mesenchymal Hedgehog signaling characterizes Barrett's metaplasia, Gastroenterology [P], vol 138, issue 5, WB Saunders Co., United States, pp. 1810-1822.e2.

Tang, B.C., Fu, J., Watkins, D.N., Hanes, J., 2010, Enhanced efficacy of local etoposide delivery by poly(ether-anhydride) particles against small cell lung cancer in vivo, Biomaterials [P], vol 31, Elsevier BV, Netherlands, pp. 339-344.

Buonamici, S., Williams, J., Morrissey, M., Wang, A., Guo, R., Vattay, A., Hsiao, K., Yuan, J., Green, J., Ospina, B., Yu, Q., Ostram, L., Fordjour, P., Anderson, D.L., Monahan, J.E., Kelleher, J.F., Peukert, S., Pan, S., Wu, X., Maira, S., Briggs, K.J., Watkins, D.N., Yao, Y., Lengauer, C., Warmuth, M., Sellers, W.R., Dorsch, M., Garcia-Echeverria, C., 2010, Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma, Science Translational Medicine [P], vol 2, issue 51 (51ra70), American Association for the Advancement of Science, United States, pp. 1-8.

Koskimaki, J.E., Karagiannis, E.D., Tang, B.C., Hammers, H., Watkins, D.N., Pili, R., Popel, A.S., 2010, Pentastatin-1, a collagen IV derived 20-mer peptide, suppresses tumor growth in a small cell lung cancer xenograft model, BMC Cancer [P], vol 10, issue 29, BioMed Central Ltd, UK, pp. 1-7.

Lin, T., Wang, Q., Brown, P., Peacock, C., Merchant, A., Brennan, S., Jones, E., McGovern, K., Watkins, D., Sakamoto, K., Matsui, W., 2010, Self-renewal of acute lymphocytic leukemia cells is limited by the Hedgehog pathway inhibitors cyclopamine and IPI-926, PLoS ONE [P], vol 5, issue 12 (e15262), Public Library of Science, United States, pp. 1-8.

Daniel, V.C., Marchionni, L., Hierman, J.S., Rhodes, J.T., Devereux, W.L., Rudin, C.M., Yung, R., Parmigiani, G., Dorsch, M., Peacock, C.D., Watkins, D.N., 2009, A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro, Cancer Research [P], vol 69, issue 8, American Association for Cancer Research, United States, pp. 3364-3373.

Jiang, T., Collins, B.J., Jin, N., Watkins, D.N., Brock, M.V., Matsui, W., Nelkin, B.D., Ball, D.W., 2009, Achaete-scute complex homologue 1 regulates tumor-initiating capacity in human small cell lung cancer, Cancer Research [P], vol 69, issue 3, American Association for Cancer Research, United States, pp. 845-854.

Peacock, C.D., Watkins, D.N., 2008, Cancer stem cells and the ontogeny of lung cancer, Journal of Clinical Oncology, vol 26, issue 17, American Society of Clinical Oncology, United States, pp. 2883-2889.

Matsui, W., Wang, Q., Barber, J.P., Brennan, S., Smith, B.D., Borrello, I., McNiece, I., Lin, L., Ambinder, R.F., Peacock, C.D., Watkins, D.N., Huff, C.A., Jones, R.J., 2008, Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance, Cancer Research, vol 68, issue 1, American Association for Cancer Research (A AC R), United States, pp. 190-197.

Briggs, K.J., Corcoran-Schwartz, I.M., Zhang, W., Harcke, T., Devereux, W.L., Baylin, S.B., Eberhart, C.G., Watkins, D.N., 2008, Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma, Genes and Development, vol 22, issue 6, Cold Spring Harbor Laboratory Press, USA, UK, pp. 770-785.

Zhang, W., Glockner, S.C., Guo, M., Machida, E.O., Wang, D.H., Easwaran, H., Van Neste, L., Herman, J.G., Schuebel, K.E., Watkins, D.N., Ahuja, N., Baylin, S.B., 2008, Epigenetic inactivation of the canonical Wnt antagonist SRY-box containing gene 17 in colorectal cancer, Cancer Research, vol 68, issue 8, American Association for Cancer Research (A AC R), United States, pp. 2764-2772.

Briggs, K.J., Eberhart, C.G., Watkins, D.N., 2008, Just say no to ATOH: how HIC1 methylation might predispose medulloblastoma to lineage addiction, Cancer Research, vol 68, issue 21, American Association for Cancer Research (AACR), USA, pp. 8654-8656.

Rudin, C.M., Hann, C.L., Peacock, C.D., Watkins, D.N., 2008, Novel systemic therapies for small cell lung cancer, Journal of the National Comprehensive Cancer Network, vol 6, issue 3, Jones and Bartlett Publishers Inc., United States, pp. 315-322.

Hann, C.L., Daniel, V.C., Sugar, E.A., Dobromilskaya, I., Murphy, S.C., Cope, L., Lin, X., Hierman, J.S., Wilburn, D.L., Watkins, D.N., Rudin, C.M., 2008, Therapeutic efficacy of ABT-737, a selective inhibitor of BCL-2, in small cell lung cancer, Cancer Research, vol 68, issue 7, American Association for Cancer Research (A AC R), USA, pp. 2321-2328.

Biankin, S.A., Collector, M.I., Biankin, A.V., Brown, L.J., Kleeberger, W., Devereux, W.L., Zahnow, C.A., Baylin, S.B., Watkins, D.N., Sharkis, S.J., Leach, S.D., 2007, A histological survey of green fluorescent protein expression in 'green' mice: implications for stem cell research, Pathology, vol 39, issue 2, Taylor & Francis Ltd, UK, pp. 247-251.

Ohm, J.E., McGarvey, K.M., Yu, X., Cheng, L., Schuebel, K.E., Cope, L., Mohammad, H.P., Chen, W., Daniel, V.C., Yu, W., Berman, D.M., Jenuwein, T., Pruitt, K., Sharkis, S.J., Watkins, D.N., Herman, J.G., Baylin, S.B., 2007, A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing, Nature Genetics, vol 39, issue 2, Nature Publishing Group, USA, pp. 237-242.

Nikolaidis, N., Chalkia, D., Watkins, D.N., Barrow, R.K., Snyder, S.H., van Rossum, D.B., Patterson, R.L., 2007, Ancient origin of the new developmental superfamily DANGER, PLOS One, vol 2, issue 2 (e204), Public Library of Science, United States, pp. 1-15.

Peacock, C.D., Wang, Q., Gesell, G.S., Corcoran-Schwartz, I.M., Jones, E., Kim, J., Devereux, W.L., Rhodes, J.T., Huff, C.A., Beachy, P.A., Watkins, D.N., Matsui, W., 2007, Hedgehog signaling maintains a tumor stem cell compartment in multiple myeloma, Proceedings of the National Academy of Sciences of the United States of America, vol 104, issue 10, National Academy of Sciences, USA, pp. 4048-4053.

Lam, W.K., Watkins, D.N., 2007, Lung cancer: Future directions, Respirology, vol 12, issue 4, Blackwell Publishing, Odon England, pp. 471-477.

Reddy, P.S., Burroughs, K.D., Hales, L.M., Ganesh, S., Jones, B.H., Idamakanti, N., Hay, C., Li, S.S., Skele, K.L., Vasko, A., Yang, J., Watkins, D.N., Rudin, C.M., Hallenbeck, P.L., 2007, Seneca Valley virus, a systemically deliverable oncolytic picornavirus, and the treatment of neuroendocrine cancers., Journal of the National Cancer Institute, vol 99, issue 21, Oxford Univ Press Inc, UK, USA, pp. 1623-1633.

van Rossum, D.B., Patterson, R.L., Cheung, K., Barrow, R.K., Syrovatkina, V., Gessell, G.S., Burkholder, S.G., Watkins, D.N., Foskett, J.K., Snyder, S.H., 2006, DANGER, a novel regulatory protein of inositol 1,4,5-trisphosphate-receptor activity, Journal of Biological Chemistry, vol 281, issue 48, American Society for Biochemistry and Molecular Biology, Inc., USA, pp. 37111-37116.

Daniel, V.C., Peacock, C.D., Watkins, D.N., 2006, Developmental signalling pathways in lung cancer, Respirology, vol 11, issue 3, Blcakwell Publishing, UK, pp. 234-240.

Pruitt, K., Zinn, R.L., Ohm, J.E., McGarvey, K.M., Kang, S.L., Watkins, D.N., Herman, J.G., Baylin, S.B., 2006, Inhibition of SIRT1 reactivates silenced cancer genes without loss of promoter DNA hypermethylation., PL o S Genetics, vol 2, issue 3 (e40), Piblic Library of Science, United States, pp. 0344-0352.

Suzuki, H., Watkins, D.N., Jair, K., Schuebel, K.E., Markowitz, S.D., Chen, W.D., Pretlow, T.P., Yang, B., Akiyama, Y., van Engeland, M., Toyota, M., Tokino, T., Hinoda, Y., Imai, K., Herman, J.G., Baylin, S.B., 2004, Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer, Nature Genetics, vol 36, issue 4, Nature Publishing Group, USA, pp. 417-422.

Watkins, D.N., Peacock, C.D., 2004, Hedgehog signalling in foregut malignancy, Biochemical Pharmacology, vol 68, issue 6, Pergamon-Elsevier Science Ltd, UK, pp. 1055-1060.

Akiyama, Y., Watkins, D.N., Suzuki, H., Jair, K., van Engeland, M., Esteller, M., Sakai, H., Ren, C., Yuasa, Y., Herman, J.G., Baylin, S.B., 2003, GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer, Molecular and Cellular Biology, vol 23, issue 23, American Society for Microbiology, USA, pp. 8429-8439.

Watkins, D.N., Berman, D.M., Baylin, S.B., 2003, Hedgehog signaling: Progenitor phenotype in small-cell lung cancer, Cell Cycle, vol 2, issue 3, Landes Bioscience, USA, pp. 196-198.

Watkins, D.N., Berman, D.M., Burkholder, S.G., Wang, B., Beachy, P.A., Baylin, S.B., 2003, Hedgehog signalling within airway epithelial progenitors and in small-cell lung cancer, Nature, vol 422, issue 6929, Nature Publishing Group, UK, pp. 313-317.

Chen, W., Zeng, X., Carter, M.G., Morrell, C.N., Yen, R.C., Esteller, M., Watkins, D.N., Herman, J.G., Mankowski, J.L., Baylin, S.B., 2003, Heterozygous disruption of Hic1 predisposes mice to a gender-dependent spectrum of malignant tumors, Nature Genetics, vol 33, issue 2, Nature America Inc, New York USA, pp. 197-202.

Berman, D.M., Karhadkar, S.S., Maitra, A., de Oca, R.M., Gerstenblith, M.R., Briggs, K.J., Parker, A.R., Shimada, Y., Eshleman, J.R., Watkins, D.N., Beachy, P.A., 2003, Widespread requirement for Hedgehog ligand stimulation in growth of digestive tract tumours, Nature, vol 425, issue 6960, Nature Publishing Group, Uk, pp. 846-851.

Berman, D.M., Karhadkar, S.S., Hallahan, A.R., Pritchard, J.I., Eberhart, C.G., Watkins, D.N., Chen, J.K., Cooper, M.K., Taipale, J., Olson, J.M., Beachy, P.A., 2002, Medulloblastoma growth inhibition by hedgehog pathway blockade, Science, vol 297, issue 5586, Amer Assoc Advancement Science, Washington DC USA, pp. 1559-1561.

Sriuranpong, V., Borges, M.W., Strock, C.L., Nakakura, E.K., Watkins, D.N., Blaumueller, C.M., Nelkin, B.D., Ball, D.W., 2002, Notch signaling induces rapid degradation of achaete-scute homolog 1, Molecular and Cellular Biology, vol 22, issue 9, Amer Soc Microbiology, Washington DC USA, pp. 3129-3139.

Ray, S., Watkins, D.N., Misso, N.L.A., Thompson, P.J., 2002, Oxidant stress induces gamma-glutamylcysteine synthetase and glutathione synthesis in human bronchial epithelial NCI-H292 cells, Clinical and Experimental Allergy, vol 32, issue 4, Blackwell Science Ltd, Oxon England, pp. 571-577.

Teaching Commitment

- Lecturer, Developmental Biology Dev3032

- Medical Student Clinical Teaching, Monash Medical Centre

- Mentoring Postdoctoral Fellows, MD Students, PhD Students and BMedSci Students

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Deregulated IL-6 signalling as a key molecular bridge linking the pathogenesis of emphysema and L/C.
Supervisors:
Jenkins, B (Main), Ruwanpura, S (Associate), Watkins, D (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Development of Primary Xenografts as Platform for Personalised Medicine in NonSmall Cell Lung Cancer.
Supervisors:
Watkins, D (Main).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Functional characterization of the tumour suppressor gene hypermethylated in cancer-1 (HIC1).
Supervisors:
Cain, J (Joint), Watkins, D (Joint-co).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Mechanisms of platinum chemoresistance in lung cancer.
Supervisors:
Watkins, D (Main), Rossello, F (Associate).

Completed Supervision

Student:
Nguyen, H.
Program of Study:
Candidate markers of epithelial stem/progenitor cells in human endometrium and endomertrial cancer. (PHD) 2011.
Supervisors:
Gargett, C (Main), Watkins, D (Associate).