Laura Genovesi is a Cure Brain Cancer Foundation Research Fellow within the Paediatric Brain Cancer Laboratory headed by Professor Brandon Wainwright.
Dr Genovesi is a cancer biologist specialising in in vivo pre-clinical models to dissect the mechanisms underpinning growth of medulloblastoma, a paediatric brain tumour. They were awarded their PhD in 2012 (University of Western Australia), where they studied the role of microRNAs in the transformation of human neural stem cells to Medulloblastoma. They relocated to the University of Queensland to commence her post-doctoral studies in the laboratory of Prof. Brandon Wainwright. Dr Genovesi's post-doctoral research focuses on discovering and targeting the genetic networks that drive medulloblastoma. Their work has contributed to defining regulatory networks underlying the growth of medulloblastoma and the therapeutic application of CDK4/6 inhibitors in the treatment of medulloblastoma. Most recently, her work has characterised the status of the blood brain barrier in some of the most widely used patient derived orthotopic xenograft models of medulloblastoma. Dr Laura Genovesi’s research is now focused on understanding the intrinsic and adaptive plasticity of tumour cells and acellular components of the brain tumour microenvironment (TME) that drive tumour progression and determine response to therapy. Their research integrates integrates diverse preclinical model systems including patient-derived in vivo models and dynamic ex vivo 3D hydrogel models with innovative spatial transcriptomics/ imaging and advanced computational cancer biology aiming to ultimately to improve the lives of children diagnosed with brain tumours.
Medulloblastoma (MB) is the leading cause of cancer-related mortality and morbidity in children. Survival rates have not significantly changed for thirty years and survivors are faced with lifelong side effects from their treatments including cognitive decline, developmental defects and other cancers. Additionally, few effective therapies are available for patients with high-risk disease, such as those with MYC- amplified Group 3 (Gp3) MB. New targeted therapies are urgently needed for children diagnosed with medulloblastoma; to increase survival rates and improve quality of life for children diagnosed with this disease. Dr Genovesi's research has made significant strides in this area, generating a genetic map to find new pathways that are driving aggressive forms of this disease. Using this map, two existing classes of drugs apprved for breast cancer have been repurposed and identified as effective therapies for this disease. One of these classes of drugs is currently in clinical trial for children diagnosed with a range of brain tumours, with data from this project confirming these agents have an even greater effect when combined with standard therapy for children diagnosed with this disease. Outcomes from this research program can be used to support the next phase of clinical trials for these agents, with the inclusion of this new targeted therapy into standard of care aiming to result in greater survival rates for patients diagnosed with this disease.
Journal Article: MDB-42. UNCOVERING DYNAMIC CHANGES IN MEDULLOBLASTOMA ASSOCIATED VASCULATURE IN ZEBRAFISH
Morris, Elysse, Daignault-Mill, Sheena, Ju, Robert J, da Silva, Jason, Gordon, Emma, Wainwright, Brandon, Stehbens, Samantha, Genovesi, Laura and Lagendijk, Anne (2023). MDB-42. UNCOVERING DYNAMIC CHANGES IN MEDULLOBLASTOMA ASSOCIATED VASCULATURE IN ZEBRAFISH. Neuro-Oncology, 25 (Supplement_1), i71-i71. doi: 10.1093/neuonc/noad073.274
Vo, Tuan, Balderson, Brad, Jones, Kahli, Ni, Guiyan, Crawford, Joanna, Millar, Amanda, Tolson, Elissa, Singleton, Matthew, Kojic, Marija, Robertson, Thomas, Walters, Shaun, Mulay, Onkar, Bhuva, Dharmesh D., Davis, Melissa J., Wainwright, Brandon J., Nguyen, Quan and Genovesi, Laura A. (2023). Spatial transcriptomic analysis of Sonic hedgehog medulloblastoma identifies that the loss of heterogeneity and promotion of differentiation underlies the response to CDK4/6 inhibition. Genome Medicine, 15 (1) 29. doi: 10.1186/s13073-023-01185-4
Conference Publication: Applying spatial omics and computational integrative analyses to study drug responses and cancer immune cell interactions
Tan, Xiao, Causer, Andrew, Vo, Tuan Quang Anh, Ma, Ning, Cheikh, Bassem Ben, Genovesi, Laura, Gonzalez-Cruz, Jazmina, Nguyen, Quan and Braubach, Oliver (2023). Applying spatial omics and computational integrative analyses to study drug responses and cancer immune cell interactions. AACR Annual Meeting 2023, Orlando, FL United States, 14-19 April 2023. Philadelphia, PA United States: American Association for Cancer Research. doi: 10.1158/1538-7445.am2023-4703
(2023–2024) The Cure Starts Now Foundation
Medulloblastoma plasticity, persistence, relapse and resistance
(2023) NHMRC IDEAS Grants
(2022–2026) The Cure Starts Now Australia
Investigation into network-defined novel targeted therapies for medulloblastoma
Doctor Philosophy
New treatments for children with medulloblastoma.
Doctor Philosophy
Spatial transcriptomics and Single-cell Interaction Analysis
Doctor Philosophy
MDB-42. UNCOVERING DYNAMIC CHANGES IN MEDULLOBLASTOMA ASSOCIATED VASCULATURE IN ZEBRAFISH
Morris, Elysse, Daignault-Mill, Sheena, Ju, Robert J, da Silva, Jason, Gordon, Emma, Wainwright, Brandon, Stehbens, Samantha, Genovesi, Laura and Lagendijk, Anne (2023). MDB-42. UNCOVERING DYNAMIC CHANGES IN MEDULLOBLASTOMA ASSOCIATED VASCULATURE IN ZEBRAFISH. Neuro-Oncology, 25 (Supplement_1), i71-i71. doi: 10.1093/neuonc/noad073.274
Vo, Tuan, Balderson, Brad, Jones, Kahli, Ni, Guiyan, Crawford, Joanna, Millar, Amanda, Tolson, Elissa, Singleton, Matthew, Kojic, Marija, Robertson, Thomas, Walters, Shaun, Mulay, Onkar, Bhuva, Dharmesh D., Davis, Melissa J., Wainwright, Brandon J., Nguyen, Quan and Genovesi, Laura A. (2023). Spatial transcriptomic analysis of Sonic hedgehog medulloblastoma identifies that the loss of heterogeneity and promotion of differentiation underlies the response to CDK4/6 inhibition. Genome Medicine, 15 (1) 29. doi: 10.1186/s13073-023-01185-4
Morris, Elysse K., Daignault-Mill, Sheena, Stehbens, Samantha J., Genovesi, Laura A. and Lagendijk, Anne K. (2023). Addressing blood-brain-tumor-barrier heterogeneity in pediatric brain tumors with innovative preclinical models. Frontiers in Oncology, 13 1101522, 1-9. doi: 10.3389/fonc.2023.1101522
Adolphe, Christelle, Millar, Amanda, Kojic, Marija, Barkauskas, Deborah S., Sundstrom, Anders, Swartling, Fredrik J., Hediyeh-zadeh, Soroor, Tan, Chin Wee, Davis, Melissa J., Genovesi, Laura A. and Wainwright, Brandon J. (2021). SOX9 defines distinct populations of cells in SHH medulloblastoma but is not required for Math1-driven tumour formation. Molecular Cancer Research, 19 (11), 1831-1839. doi: 10.1158/1541-7786.mcr-21-0117
Genovesi, Laura A., Millar, Amanda, Tolson, Elissa, Singleton, Matthew, Hassall, Emily, Kojic, Marija, Brighi, Caterina, Girard, Emily, Andradas, Clara, Kuchibhotla, Mani, Bhuva, Dharmesh D., Endersby, Raelene, Gottardo, Nicholas G., Bernard, Anne, Adolphe, Christelle, Olson, James M., Taylor, Michael D., Davis, Melissa J. and Wainwright, Brandon J. (2021). Systems pharmacogenomics identifies novel targets and clinically actionable therapeutics for medulloblastoma. Genome Medicine, 13 (1) 103, 103. doi: 10.1186/s13073-021-00920-z
Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype
Kojic, Marija, Gawda, Tomasz, Gaik, Monika, Begg, Alexander, Salerno-Kochan, Anna, Kurniawan, Nyoman D., Jones, Alun, Drożdżyk, Katarzyna, Kościelniak, Anna, Chramiec-Głąbik, Andrzej, Hediyeh-Zadeh, Soroor, Kasherman, Maria, Shim, Woo Jun, Sinniah, Enakshi, Genovesi, Laura A., Abrahamsen, Rannvá K., Fenger, Christina D., Madsen, Camilla G., Cohen, Julie S., Fatemi, Ali, Stark, Zornitza, Lunke, Sebastian, Lee, Joy, Hansen, Jonas K., Boxill, Martin F., Keren, Boris, Marey, Isabelle, Saenz, Margarita S., Brown, Kathleen ... Wainwright, Brandon J. (2021). Elp2 mutations perturb the epitranscriptome and lead to a complex neurodevelopmental phenotype. Nature Communications, 12 (1) 2678, 2678. doi: 10.1038/s41467-021-22888-5
Adolphe, Christelle, Xue, Angli, Fard, Atefeh Taherian, Genovesi, Laura A., Yang, Jian and Wainwright, Brandon J. (2021). Genetic and functional interaction network analysis reveals global enrichment of regulatory T cell genes influencing basal cell carcinoma susceptibility. Genome Medicine, 13 (1) 19, 19. doi: 10.1186/s13073-021-00827-9
Patient derived orthotopic xenograft models of Medulloblastoma lack a functional blood brain barrier
Genovesi, Laura A., Puttick, Simon, Millar, Amanda, Kojic, Marija, Ji, Pengxiang, Lagendijk, Anne K., Brighi, Caterina, Bonder, Claudine S, Adolphe, Christelle and Wainwright, Brandon J. (2020). Patient derived orthotopic xenograft models of Medulloblastoma lack a functional blood brain barrier. Neuro-Oncology, 23 (5), 732-742. doi: 10.1093/neuonc/noaa266
Brighi, Caterina, Reid, Lee, Genovesi, Laura A., Kojic, Marija, Millar, Amanda, Bruce, Zara, White, Alison L., Day, Bryan W., Rose, Stephen, Whittaker, Andrew K. and Puttick, Simon (2020). Comparative study of preclinical mouse models of high-grade glioma for nanomedicine research: the importance of reproducing blood-brain barrier heterogeneity. Theranostics, 10 (14), 6361-6371. doi: 10.7150/thno.46468
MR-guided focused ultrasound increases antibody delivery to nonenhancing high-grade glioma
Brighi, Caterina, Reid, Lee, White, Alison L., Genovesi, Laura A., Kojic, Marija, Millar, Amanda, Bruce, Zara, Day, Bryan W., Rose, Stephen, Whittaker, Andrew K. and Puttick, Simon (2020). MR-guided focused ultrasound increases antibody delivery to nonenhancing high-grade glioma. Neuro-Oncology Advances, 2 (1) vdaa030, 1-12. doi: 10.1093/noajnl/vdaa030
Elongator mutation in mice induces neurodegeneration and ataxia-like behavior
Kojic, Marija, Gaik, Monika, Kiska, Bence, Salerno-Kochan, Anna, Hunt, Sarah, Tedoldi, Angelo, Mureev, Sergey, Jones, Alun, Whittle, Belinda, Genovesi, Laura A., Adolphe, Christelle, Brown, Darren L., Stow, Jennifer L., Alexandrov, Kirill, Sah, Pankaj, Glatt, Sebastian and Wainwright, Brandon J. (2018). Elongator mutation in mice induces neurodegeneration and ataxia-like behavior. Nature Communications, 9 (1) 3195, 3195. doi: 10.1038/s41467-018-05765-6
Sangar, Michelle L. Cook, Genovesi, Laura A., Nakamoto, Madison W., Davis, Melissa J., Knobluagh, Sue E., Ji, Pengxiang, Millar, Amanda, Wainwright, Brandon J. and Olson, James M. (2017). Inhibition of CDK4/6 by palbociclib significantly extends survival in medulloblastoma patient-derived xenograft mouse models. Clinical Cancer Research, 23 (19), 5802-5813. doi: 10.1158/1078-0432.CCR-16-2943
Harris, Lachlan, Genovesi, Laura A., Gronostajski, Richard M., Wainwright, Brandon J. and Piper, Michael (2015). Nuclear factor one transcription factors: divergent functions in developmental versus adult stem cell populations. Developmental Dynamics, 244 (3), 227-238. doi: 10.1002/dvdy.24182
Genovesi, Laura A., Ng, Ching Ging, Davis, Melissa J., Remke, Marc, Taylor, Michael D., Adams, David J., Rust, Alistair G., Ward, Jerrold M., Ban, Kenneth H., Jenkins, Nancy A., Copeland, Neal G. and Wainwright, Brandon J. (2013). Sleeping Beauty mutagenesis in a mouse medulloblastoma model defines networks that discriminate between human molecular subgroups. Proceedings of the National Academy of Sciences of the United States of America, 110 (46), E4325-E4334. doi: 10.1073/pnas.1318639110
Genovesi, Laura A., Anderson, Denise, Carter, Kim W., Giles, Keith M. and Dallas, Peter B. (2012). Identification of suitable endogenous control genes for microRNA expression profiling of childhood medulloblastoma and human neural stem cells. BMC Research Notes, 5 (1) 507, 507.1-507.12. doi: 10.1186/1756-0500-5-507
Genovesi, Laura A., Carter, Kim W., Gottardo, Nicholas G., Giles, Keith M. and Dallas, Peter B. (2011). Integrated analysis of miRNA and mRNA expression in childhood Medulloblastoma compared with neural stem cells. PLoS One, 6 (9) e23935, e23935.1-e23935.12. doi: 10.1371/journal.pone.0023935
Tan, Xiao, Causer, Andrew, Vo, Tuan Quang Anh, Ma, Ning, Cheikh, Bassem Ben, Genovesi, Laura, Gonzalez-Cruz, Jazmina, Nguyen, Quan and Braubach, Oliver (2023). Applying spatial omics and computational integrative analyses to study drug responses and cancer immune cell interactions. AACR Annual Meeting 2023, Orlando, FL United States, 14-19 April 2023. Philadelphia, PA United States: American Association for Cancer Research. doi: 10.1158/1538-7445.am2023-4703
Vo, Tuan, Balderson, Brad, Jones, Kahli, Crawford, Joanna, Millar, Amanda, Tolson, Elissa, Ruitenberg, Marc, Robertson, Thomas, Bhuva, Dharmesh, Davis, Melissa, Wainwright, Brandon, Nguyen, Quan and Genovesi, Laura (2022). MEDB-06. Spatial transcriptomic analysis of Sonic Hedgehog Medulloblastoma identifies that loss of heterogeneity and induced differentiation underlies the response to CDK4/6 inhibition. International Symposium on Pediatric Neuro-Oncology, Hamburg, Germany, 12–15 June 2022. Cary, NC, United States: Oxford University Press. doi: 10.1093/neuonc/noac079.381
Targeting Apoptosis as a Novel Therapy for Myc-Driven Medulloblastoma
Ji, Pengxiang, Genovesi, Laura, He, Yaowu, Hooper, John and Wainwright, Brandon (2016). Targeting Apoptosis as a Novel Therapy for Myc-Driven Medulloblastoma. 17th International Symposium on Pediatric Neuro-Oncology (ISPNO), Liverpool England, 12-15 June 2016. United States: Oxford University Press.
Mouse Functional Genomics to Predict Novel Drug Targets for All Subgroups of Medulloblastoma
Genovesi, Laura, Ji, Pengxiang, Davis, Melissa, Ching Ging Ng, Remke, Marc, Taylor, Michael, Cho, Yoon-Jae, Jenkins, Nancy, Copeland, Neil and Wainwright, Brandon (2014). Mouse Functional Genomics to Predict Novel Drug Targets for All Subgroups of Medulloblastoma. 16th International Symposium on Pediatric Neuro-Oncology (ISPNO), Singapore, Singapore, 28 June - 02 July 2014. Cary, NC United States: Oxford University Press. doi: 10.1093/neuonc/nou074
(2023–2024) The Cure Starts Now Foundation
Medulloblastoma plasticity, persistence, relapse and resistance
(2023) NHMRC IDEAS Grants
(2022–2026) The Cure Starts Now Australia
A new and effective combination therapy for children with brain cancer
(2022) Preclinical and Clinical Early Career Research
Travel Award to attend ISPNO conference and Uppsala brain tumour conference
(2022) RCDF Travel Grant Award
(2021–2024) NHMRC IDEAS Grants
(2021–2022) Preclinical and Clinical Early Career Research
(2020–2024) Brainchild Foundation
(2020–2022) The Children's Hospital Foundation
(2019–2020) The Children's Hospital Foundation
(2018–2021) Cure Brain Cancer Foundation
(2018) Telethon Kids Institute
Dr Laura Genovesi - Maternity Funding (Advance Queensland Women's Academic Fund)
(2017–2018) Queensland Government Advance Queensland Women's Academic Fund
Investigation into network-defined novel targeted therapies for medulloblastoma
Doctor Philosophy — Principal Advisor
Other advisors:
New treatments for children with medulloblastoma.
Doctor Philosophy — Associate Advisor
Other advisors:
Spatial transcriptomics and Single-cell Interaction Analysis
Doctor Philosophy — Associate Advisor
Other advisors:
Assessing combinations of molecularly targeted agents as novel therapies for Medulloblastoma
Doctor Philosophy — Associate Advisor
Other advisors:
Investigating the role of the blood vasculature in Medulloblastoma progression using zebrafish models
Doctor Philosophy — Associate Advisor
Other advisors:
Quantifying tumour heterogeneity by spatial transcriptomics, imaging, and computational modelling to identify rare cancer cells driving tumour recurrence
Doctor Philosophy — Associate Advisor
Other advisors:
Targeting Apoptosis as A Novel Therapy for Medulloblastoma
(2018) Doctor Philosophy — Associate Advisor
Other advisors:
Genetic Regulation of Development and Disorders of the Cerebellum
(2016) Doctor Philosophy — Associate Advisor
Other advisors: