Group Leader
Translational Oncology Discovery
+61 7 3845 3506bill.dougall@qimrberghofer.edu.au
Dr William Dougall leads the Translational Oncology Discovery Laboratory at QIMRB. He has authored more than 80 peer-reviewed publications (>12,000 citations) and holds seven patents. Prior to his appointment at QIMRB, he worked in industry and led multiple oncology drug development programs through IND and Phase I testing, including world-wide registration of denosumab, an agent widely used in oncology. He was the first to clone the novel TNF ligand/TNF receptor pair RANKL/RANK and demonstrate an obligate role for this pathway in development of lymph nodes, mammary glands and osteoclasts. More recently, he has provided new insights into RANKL biology relevant to cancer immunotherapy as well as characterized two other novel targets for cancer immunotherapy. Dr Dougall has extensive experience with preclinical tumor immunology models, clinical biomarker development (including IHC and transcriptomics) and has contributed to the translational design of over 20 oncology clinical trials (PI-III).
2018-2020: Partner, Cascadia Drug Development Group (theCDDG.com), Seattle, WA
2016-2018: Group Leader and Senior Principal Research Fellow, Translational Cancer Immunotherapy, QIMR Berghofer Medical Research Institute, Herston, QLD
2011-2016: Research Scientific Director, Therapeutic Innovation Unit (TIU), Amgen Inc. Seattle, WA
2002-2011: Research Scientific Director, Department of Hematology/Oncology Research, Amgen Inc., Seattle, WA
1994-2002: Senior Staff Scientist, Associate Director, Department of Molecular Biology, Immunex Corp., Seattle, WA
https://www.scopus.com/authid/detail.uri?authorId=6701416820
https://orcid.org/0000-0001-9487-251X
The Translational Cancer Discovery Group is particularly interested in engineering novel antibody-based cancer therapies that can directly target certain tumour cells and, simultaneously, also targets key immune cell proteins, therefore combining two cancer therapy approaches in one drug. We are validating these drug candidates using genetically-engineered mouse models of cancer along with state-of-the art flow cytometry, transcriptomics analysis and other tissue imaging platforms.
Importantly, our approach to cancer drug development is informed by the “reverse translational research” paradigm. This means that we utilise cutting-edge translational experiments using patient-derived materials from on-going cancer clinical trials to help understand mechanisms and design the next generation of cancer therapies. Currently, we are engaged in clinical trial activities that include experimental treatments for patients with non-small cell lung cancer, head and neck squamous cell carcinoma, colorectal cancer and breast cancer.
First to clone RANK and RANKL and defined an obligate role for RANK and RANKL in lymph node formation, mammary gland development and osteoclastogenesis, which is the process responsible for bone erosions in many human pathologies including bone metastasis, osteoporosis and rheumatoid arthritis.
Led the drug development program for denosumab (anti-RANKL mAb) in oncology. Denosumab is approved world-wide for a number of oncology indications.
In collaboration with WEHI, defined the novel mechanism by which RANKL initiates breast cancer in BRCA1-carriers (Nature Med. 2016). These studies rationalised two clinical trials: BRCA-D (PI translational study in BRCA1-carriers at WEHI) and an ongoing, international Phase III clinical trial (BRCA-P; BCT 1801) to test whether denosumab will prevent breast cancer in women carrying a BRCA1 mutation
Defined RANKL blockade as a strategy to overcome resistance to checkpoint inhibitors (Clin Cancer Res 2017; OncoImmunol., 2018); these studies triggered the P1b/PII study of neoadjuvant denosumab plus nivolumab in patients with in NSCLC [POCORN study, in collaboration with Assoc Prof Hughes (RBWH) and Dr. Liz Ahern (Monash Univ.)]
Demonstrated the anti-tumour effectiveness of targeting the novel T- and NK- inhibitory receptor CD96 (Cancer Immunol. Res., 2019)
Contributed to development of CD96, CD155 and DNAM-1 as novel immunotherapy targets and as IHC biomarkers to define melanoma patient response to immunotherapies (in collaboration with multiple QIMRB researchers); (Clin Cancer Res. 2020; Immunity, 2020)
2021: Society for Immunotherapy of Cancer
2021: American Association of Cancer Research
2011: Recipient of the Prix Galien USA Award for Best Biotechnology Product (for Prolia® and XGEVA®).
2011: Recipient of the Washington Biotechnology and Biomedical Association Innovation Award
2008: Dr. Alvin J. Thompson Award; Northwest Association for Biomedical Research
2001: Immunex Scientific Achievement Award
1990-1994: Post-doctoral Fellow, University of Pennsylvania, Div. of Immunology
1990: PhD. in Biochemistry and Molecular Biology, University of Florida
1985: BS. in Cell Biology, University of Florida