Targeting STAT3 in CAFs to improve immunotherapies in advanced colon cancer

2021 Honours opportunity

Supervisors: Prof Matthias Ernst and Dr Amr Allam

Laboratory: Cancer and Inflammation

Subjects prerequisites:MED3LAB, MED3PRJ and/or GEN3LAB

The tumour microenvironment plays an integral role in promoting tumour progression and triggering the onset of metastasis. Remodeling of the tumour microenvironment is regulated via complex cross-talk between tumour cells and the host’s resident stromal cells that comprise the tumour microenvironment (TME). Cancer-associated fibroblasts (CAFs) are stromal cells, which play a pivotal role in remodeling the TME to promote tumour development and enable tumour cells to evade immune responses. Recently, the cancer stemness protein, STAT3 was reported to be involved in regulating CAFs’ activities in remodeling the extra cellular matrix, which correlated with elevated tumour burden in animal models and poor prognosis in patient cohorts.

This project will take advantage of our genetically modified mouse models for STAT3 signaling and state-of-art imaging platform to investigate how STAT3 affects the crosstalk between CAFs and tumour cells within the TME of colon cancer. We will investigate the extent to which this cross-talk not only remodels the tumour microenvironment but also promote evasion of anti-tumour immune responses and limits the efficacy of current immunotherapies. This functional insight will be correlated with findings in a recent trial with human colon cancer patients and combining STAT3 inhibition with immunotherapies.

Students will work in state-of-the-art research labs at the School of Cancer Medicine /Olivia Newton-John Cancer Research Institute, which is embedded in the ONJ Cancer Centre. Students will gain experience in multidisciplinary techniques in tumour biology, immunology, molecular biology, advanced microscopy (multi-photon) and pre-clinical mouse models.

 

How do I apply?
Please complete and return your Ranked Entry Project Selection Form (available in the 2021 projects booklet) by 5pm Friday 6 November 2020 to I.Poon@latrobe.edu.au

How do I find out more?
Discover more about La Trobe University’s School of Molecular Sciences/LIMS Honours opportunities
Contact the LTU Honours Coordinator, Dr Ivan Poon
Phone: 03 9479 6488
E-mail: I.Poon@latrobe.edu.au