Research Projects
Tackling the Blood-Brain Barrier (BBB)
Discovery Theme: Blood-Brain Barrier
A major challenge in the development of new brain cancer medicines is the blood-brain barrier (BBB), a highly specialised protective barrier that separates the brain from the circulation. While highly effective at protecting the brain from toxins and infections, the BBB also prevents many cancer therapies from reaching the brain cancer directly.
To address this challenge, we undertake collaborative multidisciplinary fundamental and translational research across 4 of Australia’s leading research organisations, with the aim to discover new, innovative strategies to allow anti-cancer drugs to effectively penetrate the BBB.
Key themes in the program include:
- Understanding the development and function of the BBB in healthy brain and in the context of brain cancer, to discover new targets to manipulate the BBB.
- Developing peptide and nanobody derived delivery systems to improve transport of promising anti-cancer drugs to the brain.
- Developing screening methodologies for the identification of BBB-penetrant small molecules.
Champions
Theme Leader, New Medicines & Advanced Technologies
WEHI
Professor Guillaume Lessene trained as an organic chemist, completing his PhD at the University of Bordeaux, before undertaking postdoctoral work with Professor Feldman at Pennsylvania State University.
Since moving to the Walter and Eliza Hall Institute in 2001, his major research focus has been the development of small molecules that target apoptotic and necroptotic cell death pathways.
Since January 2019, Professor Lessene heads the New Medicines and Advanced Technologies Theme at the Institute. This multidisciplinary research theme comprises of basic research driven by structural and chemical biology, translation of basic discoveries into new medicines together with clinical research, and cutting-edge technologies.
Professor Lessene’s work targeting the BCL-2 family of proteins for cancer therapy formed the basis of a major collaboration between the Institute and two pharmaceutical companies, Genentech and AbbVie, leading to the development of venetoclax, the first BH3-mimetic approved by the US Federal Drug Agency (FDA) for the treatment of chronic lymphocytic leukaemia (CLL).
Related research projects:
Professor Guillaume Lessene
WEHI
Associate Director of Laboratory Research
Peter MacCallum Cancer Centre
Ben Hogan is a Professor at the University of Melbourne and the Peter MacCallum Cancer Centre (Australia) where he is Co-Head of the Program in Organogenesis and Cancer and runs the laboratory of Vascular Cell and Developmental Biology. Since 2023 he is also the Associate Director of Laboratory Research, overseeing ~40 research groups in diverse areas of cancer biology and research. Ben performed his PhD in myelopoiesis at the Ludwig Institute (2005, Australia) before a postdoc at the Hubrecht Institute (2006-2009, The Netherlands) where he performed the first forward genetic screens in lymphangiogenesis using zebrafish. He became a group leader in 2010 at the University of Queensland before moving to Melbourne and being promoted to Professor in 2019. Ben has been previously supported by fellowships from EMBO, the Australian Research Council and the National Health and Medical Research Council (Australia). His work has uncovered new components and effectors of the VEGFC-VEGFR3 signalling pathway that controls lymphangiogenesis in development, cancer and lymphatic disease in humans. His lab currently uses live imaging of vascular development, zebrafish and mouse genetics, functional and single cell genomic approaches and is exploring lymphatic vascular development and the formation of the blood brain barrier. In 2024, he was awarded the Judah Folkman award from the North American Vascular Biology Organisation, the leading international award for achievements for mid-career vascular biologists.
Related research projects:
Professor Ben Hogan
Peter MacCallum Cancer Centre
Associate Dean (Graduate Research) Faculty of Pharmacy Monash University
Joseph is a pharmacist and pharmaceutical scientist who graduated with a PhD from Monash University focussing on buccal mucosal drug delivery in 2004. I am an Associate Professor and Associate Dean (Graduate Research) at Faculty of Pharmacy and Pharmaceutical Sciences and Monash Institute of Pharmaceutical Sciences at Monash University. I have a passion for understanding how and why the blood-brain barrier (BBB) acts as such a fascinating interface between the CNS and periphery. My laboratory focusses on how we can overcome the BBB to improve CNS drug delivery, how the BBB alters in disease, and how we can restore the BBB to improve brain homeostasis in CNS disease.
Related research projects:
Associate Professor Joseph Nicolazzo
Monash University
Head of Screening, WEHI
A/ Prof Kym Lowes is the Head of the Screening Lab at WEHI. With over 16 years of experience in early-stage drug discovery, her laboratory exploits state-of-the-art robotic equipment to enhance the scope and speed of the pre-clinical drug discovery process. She leads a multidisciplinary team of 19 staff comprising assay development specialists, target screeners, data scientists, automation experts and engineers.
A/ Prof Lowes has a successful track record leading screening campaigns with collaborators from both academia and pharma. She has designed, implemented and led many large-scale screening campaigns and effectively executed hit to lead and lead optimisation programs. She has been a key contributor to multidisciplinary teams across a wide range of indications including oncology, infectious diseases and inflammatory diseases and various target classes including enzymes, protein-protein interactions and GPCRs.
Related research projects:
Associate Professor Kym Lowes
WEHI
Laboratory Head
University of Queensland
Dr Lagendijk finished her MSc degree in Biomedical Sciences at Radboud University Nijmegen. During her studies, Anne has worked on ovarian specification during an internship with Peter Koopman (Institute for Molecular Bioscience, Brisbane) and identified microRNAs that control pancreas development with Ronald Plasterk (Hubrecht Institute, Utrecht, the Netherlands). Through this work, Anne had developed a lasting fascination with Developmental Biology and thus for her PhD training Anne decided to stay at the Hubrecht and joined the lab of Prof Jeroen Bakkers. She identified novel regulators that control extracellular matrix homeostasis in the developing zebrafish heart which is essential for cardiac valve formation. After completing her PhD, Anne relocated to the IMB in 2012 to work as a UQ postdoctoral fellow in the lab of Prof Ben Hogan. She initiated a project studying the mechanotransduction of endothelial cell-cell junctions in vivo, in collaboration with the lab of Prof. Alpha Yap.
Anne opened her own lab at the IMB in 2019. Her team uses both zebrafish and 3D cultured human vasculature to identify the cellular mechanisms that control blood vessel integrity, both during development and in diseases such as childhood brain cancer and familial vascular malformations.
Related research projects:
Dr Anne Lagendijk
University of Queensland
Senior Research Officer, WEHI
Dr. Gabby Watson is a structural biologist and protein biochemist at WEHI. Gabby has over 10 years of experience with building understanding of disease related proteins and developing novel therapeutic molecules for the treatment of cancer and infectious diseases.
Gabby’s expertise stems from a PhD from Monash University, centred on rationally designing peptide inhibitors against a breast cancer target, followed by post-doctoral research investigating immune evasion by viruses. At WEHI, Gabby returned to her roots of developing new cancer treatments, and as part of the BCC Gabby works collaboratively to develop new nanobody-based technologies to improve transport of promising anti-cancer therapies across the blood-brain barrier.
Related research projects:
Dr Gabby Watson
WEHI