 Prof Kum Kum Khanna, Group Head, Mater Research Institute
Prof Kum Kum Khanna heads the Tumour Biology and Therapeutics laboratory at Mater Research Institute. She is best known for her work in the area of cancer biology with a specific focus on understanding cellular responses to DNA damage (DDR) and its links to genomic instability syndromes. The underlying theme of her research program is to understand the role of genome maintenance pathways in normal tissue homeostasis, in disease - in particular breast and ovarian cancer and how to exploit dysregulation of these pathways in cancers to develop new targeted therapeutic approaches.
Presentation title: Preclinical development of new therapies for aggressive forms of breast and ovarian cancers
We are interested in targeting Triple-negative breast cancer (TNBC) and high-grade serous ovarian cancers (HGSOCs), both characterized by inherent chromosomal instability (CIN), which refers to the acquisition of abnormal chromosome numbers or structures, in cancer cells. Both cancer subtypes carry high frequency of mutations in p53, BRCA1/2 and other homologous recombination repair genes, known to drive cancer development and progression. Both cancers have complex genomes, where little of their genomes remain at normal copy number which could be exploited for development of novel therapeutics. We have recently provided evidence for breast cancer subtype-specific differences in response to anti-mitotic drugs that is dependent on levels of Cep55, which allows a CIN permissive state. To decipher the mechanism by which Cep55 promotes CIN and tumorigenesis in vivo, we developed a novel “knock-in” transgenic mouse model that ubiquitously overexpresses Cep55 (Cep55Tg/Tg) and a knockout mouse model that deletes (Cep55-/-). These models demonstrate the importance of precise regulation of CEP55 levels for normal tissue homeostasis in particular brain development, and highlight the therapeutic potential of targeting CEP55 in aggressive breast cancer. CEP55 lacks any greasy pockets for small molecule binding, therefore, we are optimising strategies to chemically silence the functions of CEP55 using PROTAC-technology to tag Cep55 protein for degradation or using ASOs that target Cep55 mRNA, thereby offering a completely novel approach for cancer therapy. We are also investigating other approaches to exploit the inherent CIN and consequent proteostasis stress of these cancers.
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 Dr. Mark Adams, Senior Research Fellow, Queensland University of Technology
Mark Adams completed his PhD at the Mater Research Institute-University of Queensland in 2012 and with the support of an NHMRC Early Career Fellowship, he commenced postdoctoral work at the Translational Research Institute (TRI). Now based at KG-Q, his team’s research focus is seeking to exploit cellular programmes that regulate genome instability and cell growth to identify novel therapeutic avenues and improve therapy response for lung cancers. Dr Adams’ work is published in leading journals including Journal of Thoracic Oncology, Nature Communications and Nucleic Acids Research and has received funding support from the Queensland Government, NHMRC, the International Lung Cancer Foundation and Cancer Australia.
Presenataion title: Overcoming therapy resistance in non-small cell lung cancer
Lung cancer remains the deadliest cancer worldwide. Current therapy fails to adequately treat all people diagnosed with this disease, given only a minority of patients benefit from immunotherapy while chemotherapy and targeted therapy resistance is inevitable. Implementing diagnostic approaches to identify therapy responsive tumours and addition of novel therapeutic strategies to augment standard of care are an imperative to improve health outcomes for people living with lung cancer. In this seminar, I will discuss our research which has identified unique molecular mechanisms contributing to therapy resistance in solid malignancies. Building off these findings, our translational work seeks to prevent or delay resistance by evaluating novel biomarkers to (1) identify therapy responders and (2) determine who will benefit from our innovative therapeutic approaches to sensitise non-responders to therapy.
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 Jodi Saunus, Career Track Fellow, Mater Research
Dr Jodi Saunus is a senior fellow who specialises in translational research on metastatic breast cancer. Based at Brisbane’s Translational Research Institute, she was recruited by Mater Research in 2022 to help facilitate patient-focused research at the interface of biomedical R&D and clinical practice. Her current portfolio focuses finding new ways to improve the clinical management of aggressive breast cancer, with a focus on triple-negative breast cancer, and the prevention and treatment of brain metastases. She has excellent track record of publishing in prominent biomedical research journals (e.g., Cancer Research, Nature, Science Translational Medicine, Nature Communications and The Journal of Pathology).
Presentation title: Developing smarter treatments for brain-metastatic breast cancer
The possibility of developing brain metastases is a significant source of anxiety for breast cancer patients, particularly when entering the ‘watchful waiting’ period after initial treatment. Brain metastases usually present in the setting of disseminated disease (metastases also in the lungs, liver and/or bone), but typically produce the worst symptoms, with personality changes and severe neurological effects drastically reducing quality-of-life, and lifespan. The incidence is ~5% of all new breast cancer diagnoses, biased towards younger women with HER2+ or triple-negative disease. Each year, this equates to 700-800 Australians dying within just five years of discovering they have breast cancer.
A significant body of research indicates brain metastases are broadly refractory to systemic therapy because of pathophysiological features unique to their anatomical location, and treatment timing. Perhaps the most sweeping of all (but historically under-appreciated) is poor vascular perfusion, which exacerbates hypoxia and intratumoural heterogeneity, and impedes the delivery of systemic therapy.
Our team* is working on a treatment approach designed to circumvent some of these key constraints. Our program utilises alpha-particle endoradiotherapy as an in-situ vaccine, with additional therapeutic support to alleviate the combined local-systemic immune suppression typically seen in metastatic patients.
*AMTAR: ARC Research Hub for Advanced Manufacture of Targeted Radiopharmaceuticals
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 Dr Chenhao Zhou, Postdoctoral research fellow, The University of Queensland Frazer Institute
Dr. Chenhao Zhou obtained his PhD in Prof. Ian Frazer lab The University of Queensland Frazer Institute and developed expertise in using scRNA-seq and bioinformatics analyses as a tool to study Treg subpopulations and their T cell receptor repertoire in HPV-associated precancerous skin lesions. Dr. Chenhao Zhou is currently undertaking post-doctoral training in Prof. Kiarash Khostehrani lab at Frazer Institute where he utilizes single-cell and spatial transcriptomics to predict early-stage melanoma with poor survival and investigate the effect of UV exposure in skin cancer development.
Presentation title: Chronic UVB exposure induces early transcriptomic changes associated with skin cancer development
Exposure to ultraviolet B rays (UVB) is one of the main risk factors for developing cutaneous squamous cell carcinoma (SCC). Whether chronically UV irradiated skin with repeated suberythemal (low) doses can alter skin biology as reflected in transcriptional changes is unknown. We examined the single-cell and spatial transcriptomic profiles of murine skin exposed to chronic low-dose UVB. Compared to non-exposed control skin, UVB-exposed skin exhibited an increased basal/differentiated keratinocytes (KCs) ratio and a higher abundance of sebaceous glands and T cell infiltrates. The increase in T cell infiltrate was largely attributed to the rise in ILC2-like T cells. Downregulation of Il34-Csf1r ligand-receptor pair in UVB skin predicted impaired communication between KCs and Langerhans cells (LCs), corresponding to the diminished KC-LC spatial co-localization and a shift towards an immature LC phenotype in UVB skin. Dysregulated Il34-Csf1r signaling axis was consistently observed in precancerous skin lesions, chronically UV-exposed human healthy skin and SCC patients through analysis of single cell and spatial transcriptomics of patient samples. Thus, targeting key molecular changes induced by UVB represents a promising approach for early prevention of SCC. Our experimental models enable further evaluation of the targeted therapy of IL-34/CSF1R, which may inform the next-generation immunotherapy trials.
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 Dr Paniz Tavakoli, Postdoctoral Research Officer, QIMR Berghofer
Paniz Tavakoli Shirazi is a Postdoctoral Research Officer in the Leukaemia Research Group at QIMR-Berghofer. She completed her PhD at the University of Adelaide and the South Australian Health and Medical Research Institute (SAHMRI), where her research focused on the leukaemogenicity and therapeutic targeting of novel tyrosine kinase alterations in Acute Lymphoblastic Leukaemia. Currently, she investigates the impact of combinatorial mutations on disease phenotype, therapy resistance, and response, as well as novel treatment approaches for Acute Myeloid Leukaemia using both in vitro and in vivo genetic models.
Presentation title: Dnmt3a mutation promotes expansion of a quiescent myeloid progenitor population In Npm1c-Flt3ITD Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a highly aggressive form of blood cancer arising from multiple genetic mutations in hematopoietic stem and progenitor cells (HSPCs), leading to excessive production of immature blood cells. The effectiveness of chemotherapy in AML depends on specific combinations of genetic mutations. When mutations affecting the DNA methyltransferase DNMT3A gene co-occur with commonly mutated genes in AML, such as NPM1(encoding a shuttling protein) and tyrosine kinase FLT3, patients frequently face poor treatment outcomes after undergoing chemotherapy. However, the reasons behind this reduced response to treatment remain unclear. Here, we used genetically engineered mouse models of Npm1c-Flt3ITD driven AML with and without the Dnmt3aR878H mutation to investigate how DNMT3A mutations contribute to chemotherapy resistance. Our findings revealed that the co-expression of Dnmt3aR878H leads to the expansion of a quiescent progenitor population that persists even after chemotherapy treatment. These preliminary data suggest that Dnmt3a mutations may functionally contribute to the poor chemotherapy response observed in DNMT3AR882H-NPM1c-FLT3ITD AML cases via affecting cell cycle progression. These insights could guide the development of alternative treatments for this specific subtype of AML.
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 Dr Rochelle D'Souza, Post-doctoral researcher, QIMR Berghofer
Rochelle obtained a PhD in 2014 wherein she employed MS-based proteomics to study mammalian cell biology at the Max Plank Institute of Biochemistry in Munich, Germany. In 2016 after she joined QIMR-Berghofer, she was awarded a PdCCRS grant from Cancer Australia to understand the role of the Eph-ephrin system in glioblastoma, an aggressive form of adult brain cancer. Rochelle currently works on validating the role of ephrin A5 in glioblastoma and combining it with EphA3 to perform dual targeting of both; to tackle the challenge of tumour heterogeneity.
Presentation title: Tackling the brain cancer challenge: Using novel platforms for identifying effective therapies
The Sid Faithfull Brain Cancer Research Laboratory is dedicated to studying the most common and aggressive forms of brain cancer: Glioblastoma (GBM) in adults, and Medulloblastoma and Diffuse Midline Glioma (DMG) in children.
Our research focuses on uncovering the molecular mechanisms that drive the initiation and recurrence of these brain cancers. By understanding these processes, we aim to develop and test new, effective therapies to combat these aggressive diseases.
In my presentation I will outline novel tools we use to tackle these challenging diseases. I will also discuss our efforts to bring discovery translational research from bench to bedside and generate novel therapies to improve patient outcomes.
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