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CURRENT RESEARCH PROJECTS

Project

Research Project

Project

Research Project

Project Outline

A major challenge to detect and treat chronic inflammatory diseases such as cancer and atherosclerosis (i.e. hardening of the arteries due to fat accumulation) is to effectively deliver contrast agents and therapeutics into the pathological tissues whilst avoiding off-target binding and consequent cytotoxic effects. Our team focuses on developing tools and strategies to target the microenvironment of cancers (i.e. breast carcinoma, insulinoma and hepatocellular carcinoma) and atherosclerotic plaques for imaging and therapy.
We have recently characterised a number of small molecules (i.e. peptides) that specifically bind to the abnormal cellular and non-cellular components in cancers and atherosclerotic lesions, including blood vessels, macrophages and extracellular matrix. These tumour and plaque –specific peptides can then be used as a drug delivery agent into the pathological tissues.

Using chemical coupling and bioengineering approaches, we are now developing imaging contrast agents and therapeutics fused with these targeting peptides for in vivo applications in pre-clinical models of cancers and atherosclerosis.

Figure 1 (below): Peptide homing (green) in vivo in tumours and plaques. Source: Unpublished


Improved diagnostic imaging for detecting cancers and atherosclerosis in vivo

We have developed multifunctional nanoparticle-based system to carry contrast agents to image tumours and plaques using advanced imaging instrument including microPET/CT, MRI and confocal imaging. Importantly, these reagents are fused to the homing peptides to improve binding and accumulation deep in tumours and plaques.

Our goal is to be able to detect the developing tumours and atherosclerotic lesions at their earliest form as well as at the advanced chronic stages that are known to cause severe complications.

Figure 2 (below): PET imaging of atherosclerosis in vivo. Source: Hamzah et al. PNAS, 2011

Targeted therapy to destroy pathological lesions and reverse inflammation in cancers and atherosclerosis
Our team explores two fundamentally different therapeutic interventions which involve targeting tumours and plaques to: i) destroy selective cellular components that contribute to the progression of cancers and atherosclerosis, and ii) re-program the diseased-promoting microenvironment by reversing specific inflammatory condition in the pathological tissues.

We engineered several classes of cell-killing agents and inflammatory mediators fused with tumour and plaque targeting peptides for effective delivery. We aim to monitor the drug penetration in tumours and plaques (by imaging) and evaluate the implications of these therapeutic strategies on cancer and plaque progression.

Figure 3 (below): Immune cell infiltration in tumours in response to targeted delivery. Source: Unpublished

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Research area
Cancer, Cardiovascular Disease

Laboratory
Targeted Drug Delivery, Imaging and Therapy Laboratory

CURRENT STUDENT PROJECTS

Student Project

Designing targeted nanoparticle delivery for diagnostic imaging of cancers

Student Project

Designing targeted nanoparticle delivery for diagnostic imaging of cancers

Project Outline

New ways to effectively detect the developing malignant cancers within inaccessible parts of our body are urgently needed. Effective strategies to diagnose cancer will greatly benefit from cell-specific delivery technologies. This proposed research will exploit our discovery of novel peptide ligands that bind specifically to solid tumours in vivo. The tumour-homing moieties in these peptides can penetrate inside tumours and bind to tumour blood vessels and inflammatory macrophages. Importantly, their homing to tumours is specific; these peptides are not taken up by normal tissues.
Hence, the goal of this project is to use these tumour-homing peptides to effectively deliver imaging contrast agents into solid tumours developed in mouse models (breast carcinoma, insulinoma and hepatocellular carcinoma). Specifically, we will incorporate the blood vessel and inflammatory macrophage –binding peptides into nanoparticle formulation that carries contrast agents for positron emission tomography (PET), magnetic resonance imaging (MRI) and fluorescence imaging. We expect that our research into tumour-targeted delivery will enhance diagnosis of cancers.
This project will offer training in multidisciplinary skill sets including:

  1. Peptide coupling and nanoparticle production
  2. The use of animal models of cancers (breast carcinoma, insulinoma and hepatocellular carcinoma)
  3. The application advanced imaging instruments including PET, MRI and confocal microscopy for in vivo imaging of cancer
  4. Immunohistochemistry and biochemical assays

Contact
Assistant Professor Juliana Hamzah – [email protected]

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Chief supervisor
Assistant Professor Juliana Hamzah

Other supervisor
Professor Roger Price (Nuclear Medicine, Sir Charles Gairdner Hospital), Dr Ramana Kotamraju (Sanford-Burnham Institute of Medical Research, California, USA)

Project suitable for
Honours, PhD

Essential qualifications
background in chemistry/ biochemistry

Start date
Any time.

Student Project

Developing recombinant proteins for tumour-specific delivery

Student Project

Developing recombinant proteins for tumour-specific delivery

Project Outline

New ways to effectively treat malignant cancers within inaccessible parts of our body are urgently needed. Effective strategies to deliver anti-cancer therapeutics will greatly benefit from cell-specific delivery technologies. This proposed research will exploit our discovery of novel peptide ligands that bind specifically to solid tumours in vivo. The tumour-homing moieties in these peptides can penetrate inside tumours and bind to tumour blood vessels, inflammatory macrophages and extracellular matrix. The peptide homing to tumours is specific; these peptides are not taken up by normal tissues. Importantly, our laboratory has successfully demonstrate that when coupled to other compounds, these peptides act as delivery agents, allowing specific tumour uptake of the fusion compounds following intravenous injection.
Moreover, we show this peptide-mediated delivery approach reduces systemic toxicity associated with the native drugs. The fusion compounds have significant therapeutic use as anti-cancer reagents.
Specific training provided in this project:

  1. Engineer immune-modulating proteins fused to our tumour-homing peptides (Technical training: cloning, protein expression, production and purification).
  2. Assess bioactivity of recombinant proteins (Technical training: cell culture, FACS analysis)
  3. Evaluate in vivo tissue homing in mouse models developing insulinoma, breast carcinoma and/or hepatocellular carcinoma (Technical training: understanding of mouse tumour models, protein labelling & imaging, histology & fluorescence microscopy).
  4. Evaluate short-term and long term benefits of recombinant fusion proteins in tumour-bearing mice (for PhD candidate only; technical training: Therapeutic studies, advanced immunohistochemistry and histology analysis, microscopy and advanced tissue imaging analyses).

Contact
Assistant Professor Juliana Hamzah – [email protected]

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Chief supervisor
Assistant Professor Juliana Hamzah

Project suitable for
Honours, PhD

Essential qualifications
background in biology/molecular biology/immunology/pathology