Theme Member
Caitlin Schutz

Contact

Phone:08 8128 4340

Email: caitlin.schutz@sahmri.com

Qualifications

Bachelor of Science (Biomedical)

Research Focus

Honours Project: Investigating the efficacy of novel and combination therapies in Ph-like ALL

Relapsed Acute Lymphoblastic Leukaemia (ALL) is a significant medical problem in children and adults. Recent advances in genomic profiling techniques highlighted the genetic heterogeneity of the disease; subgroups of patients harbouring a diverse range of genetic fusions exist. Of importance are two new, high-risk ALL subtypes (Ph+ and Ph-like ALL) which respond poorly to current chemotherapeutic regimens but which are targetable with safe and highly potent drugs already in clinical use.

Ph-like ALL is characterized by different genetic alterations including fusion genes involving ABL1 and ABL2 kinases:

  • PAG1-ABL2, RCSD1-ABL2, ABL2-ZC3HAV1
  • RANBP2-ABL1, RCSD1-ABL1, SNX2-ABL1, ZMIZ1-ABL1, NUP214-ABL1, ETV6-ABL1

ABL fusions can typically be targeted with tyrosine kinase inhibitors such as dasatinib, imatinib and nilotinib, which are used to treat patients with chronic myeloid leukaemia (CML). There is also a new allosteric inhibitor called ABL001 that has demonstrated efficacy against the BCR-ABL1 fusion most commonly observed in CML patients.

This project will investigate the efficacy of ABL001 in in vitro models of leukaemia and comprises the following aims:

1) Create viral constructs containing fusion genes of interest for transduction of the Ba/F3 cell line

2) Generate cell lines stably expressing fusion genes of interest for in vitro investigations including efficacy of novel and combination drug treatments

Techniques used will include:

  • PCR and bacterial cloning of Ph-like fusions
  • Viral transfection and transduction of cell lines
  • Western blotting
  • Flow cytometry including phospho-flow and Annexin V/7AAD cell death assays

Before improved treatment of patients is effected, it is first critical to investigate the efficacy of an expanding repertoire of available therapies in the laboratory. Results from this project will be used to guide in vivo mouse models and will ultimately contribute to advancing the knowledge of drug efficacy and personalized medicine approaches in the treatment of patients with Ph-like ALL.

Get in touch
+61 8 8128 4000 info@sahmri.com
You can't miss us!
North Terrace Adelaide 5000 South Australia
Postal Address
PO BOX 11060 Adelaide 5001 South Australia
Key Partners
SAHMRI is located on the traditional lands of the Kaurna Nation.

The SAHMRI community acknowledges and respects the traditional owners, the family clans who are the Kaurna Nation from the Adelaide Plains region of South Australia. We acknowledge the clans of the Kaurna Nation and the sacred knowledge they hold for their country. We pay our respects to the Kaurna Nation, their ancestors and the descendants of these living family clans today.