Blood Cancer Therapeutics Laboratory
2017 Blood Cancer Therapeutics group L to R: Dr Daniella Brasacchio, Mr Quinton Luong, Dr Luciano Martelotto, Dr Greg Corboy, Dr Gareth Gregory, Ms Belinda Maher, A/Prof Jake Shortt (Group leader).
Blood Cancer Therapeutics Laboratory
Our research seeks to evaluate novel ways to treat haematological malignancies, with a particular focus on lymphoma and multiple myeloma. By determining the molecular mechanisms underpinning specific blood cancers, we are developing novel therapeutic strategies for translation into clinical trials. Our location within the Monash Health Translation Precinct uniquely places the laboratory in a position to develop our scientific discoveries from bench to bedside.
Major themes include: oncogenic transcription, epigenetic therapy for lymphoma, IMiD biology, lymphoma genomics and rational targeting of the MYC oncogene.
- Associate Professor Jake Shortt: Group Leader and Consultant Haematologist
- Dr Daniella Brasacchio: Research Fellow
- Dr Gareth Gregory: Early Career Fellow and Consultant Haematologist
- Dr Luciano Martelotto: Senior Research Fellow
- Ms Belinda Maher: Research Assistant
- Mr Quinton Luong: Honours student
- Dr Greg Corboy: Honorary Research Fellow and Molecular Pathologist
- Prof Ricky Johnstone: Associate Director, Laboratory Research and Head of Gene Regulation Laboratory; Peter MacCallum Cancer Centre
- Prof Andrew Spencer: Head, Myeloma Research Group, Australian Centre for Blood Diseases.
- A/Prof Arun Azad: Prostate Cancer Therapeutics Laboratory, Monash Health Translation Precinct
- Victorian Epigenetics Group
Selected recent publications
Shortt J*, Ott CJ*, Johnstone RW & Bradner JE. A chemical probe toolbox for dissecting the cancer epigenome. Nat Rev Cancer 2017; 17: 160-83. *equal contributions.
Brasacchio D et al. Epigenetic control of mitochondrial cell death through PACS1-mediated regulation of BAX/BAK oligomerization. Cell Death Differ 2017 Jan 6. doi: 10.1038/cdd.2016.119 . [Epub ahead of print].
Martelotto LG et al. Whole-genome single cell copy number profiling from formalin-fixed paraffin embedded samples. Nat Med 2017 Feb 6. doi: 10.1038/nm.4279. [Epub ahead of print].
Hogg SJ…. Shortt J* & Johnstone RW*. BET-bromodomain inhibitors engage the host immune system and regulate the expression of the immune checkpoint ligand PDL1. Cell Rep 2017; 18: 2162-74. *equal contributions.
Gregory GP…. Johnstone RW* & Shortt J*. CDK9 inhibition by dinaciclib potently suppresses Mcl-1 to induce durable apoptotic responses in aggressive Myc-driven lymphoma in vivo. Leukemia 2015; 29: 1437-41. *equal contributions.
Shortt J*, Asu AK*…Johnstone RW. The drug vehicle and solvent N-methylpyrrolidone is an immunomodulatory and antimyeloma compound. Cell Rep 2014; 7: 1009-19. *equal contributions.
- A Phase I, open label dose escalation trial of orally administered N-methyl-pyrrolidone (NMP) in patients with relapsed or refractory myeloma. NCT02468687
- A Phase IIb, open label, sequential cohort study comparing KappaMab alone to KappaMab in combination with lenalidomide and low dose dexamethasone (MRd) in relapsed / refractory multiple myeloma.
Translational evaluation of epigenetic therapies in T-cell lymphoma
T-cell lymphoma represents a significant area of unmet need in the haematology clinic, with poorer outcomes and divergent biology compared to B-cell disease. Recent genomic profiling of T-cell lymphoma has shown a unique pattern of mutations in epigenetic regulators which are distinct from B-cell lymphoma and overlap with acute myeloid leukaemia and myelodysplasia. We are evaluating the mechanisms by which epigenetically targeted drugs kill T-cell lymphoma cells, and seek to translate our discoveries into clinical trials. Contacts: Jake Shortt, Daniella Brasacchio.
Discovering new treatments for therapy-resistant multiple myeloma
Myeloma is a disease that shows unique sensitivity to drugs targeting the ubiquitin proteasome system (such as proteasome inhibitors and thalidomide analogues or ‘IMiDs’). We have performed a functional genomics screen seeking to identify new vulnerabilities in regulators of protein homeostasis within the myeloma cell. Lead candidates from this screen are now being validated as potential new druggable targets in this currently uncurable disease. Contacts: Jake Shortt, Daniella Brasacchio.
In association with the Melbourne Genomics Health Alliance ‘aggressive lymphoma flagship’, we are developing non-invasive next generation sequencing-based assays for tracking lymphoma burden and clonal evolution in patients undergoing chemo-immunotherapy with curative intent. Contacts: Gareth Gregory, Luciano Martelotto.