Are you interested in Honours at the University of Sydney? Through Honours in Applied Medical Science program at the University of Sydney, Westmead Campus, CTSR will be offering many exciting projects in 2021 that will cover your interests. Our projects include basic and translational research studies of diseases such as melanoma, non-melanoma skin cancers, cutaneous T-cell lymphoma and psoriasis. Our research laboratories are located at the Westmead Institute Medical Research (Westmead) and the Research and Education Building Laboratories (Westmead Hospital), and we also have access to various Research Core Facilities and laboratories at the University of Sydney’s main campus in Camperdown.
If you have any questions, please contact:
Prof Pablo Fernandez-Penas, Head of the Department of Dermatology on Pablo.fernandezpenas@sydney.edu.au
Or, Dr Ali Azimi, on ali.azimi@sydney.edu.au
PROJECT 1. CTCL proteomics in Formalin Fixed Paraffin Embedded (FFPE) tissue
Primary supervisor: Prof. Pablo Fernandez Penas
Co-supervisor: Dr Ali Azimi
Cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders with primary manifestation in the skin. These conditions are usually of low malignancy and evolve over extended times, often decades. However, at late stages these cancers spread to lymph nodes, viscera, and bone, and in some cases develop severe hematological manifestations. High grade cutaneous lymphomas cause substantial mortality. Currently there isn’t any good treatment options available and progress in the development of new therapies will depend on the identification of suitable target molecules. The same is true for diagnosis of cutaneous lymphomas which relies on clinical, histopathological and immunohistochemical criteria. As yet, there are no specific molecular markers for these diseases that could complement and maybe extend conventional diagnoses. In this project we propose using proteomic techniques to identify biomarkers and improves the understanding of disease mechanisms at the molecular level. Subsequently, this may aid in the development of molecular diagnostics, targeted therapies and personalized medicines.
Discipline: Applied Medical Sciences, Westmead
PROJECT 2. Proteomic analysis of Cutaneous T cell lymphomas (CTCL) using Scarless biopsy
Primary supervisor: Prof. Pablo Fernandez Penas
Co-supervisor: Dr Ali Azimi
Cutaneous lymphomas are a heterogeneous group of lymphoproliferative disorders with primary manifestation in the skin. These conditions are usually of low malignancy and evolve over extended times, often decades. However, at late stages these cancers spread to lymph nodes, viscera, and bone, and in some cases develop severe haematological manifestations. High grade cutaneous lymphomas causes substantial mortality. Currently there isn’t any good treatment options available and progress in the development of new therapies will depend on the identification of suitable target molecules. The same is true for diagnosis of cutaneous lymphomas which relies on clinical, histopathological and immunohistochemical criteria. As yet, there are no specific molecular markers for these diseases that could complement and maybe extend conventional diagnoses. In this project we propose using proteomic techniques to identify biomarkers and improves the understanding of disease mechanisms at the molecular level. Subsequently, this may aid in the development of molecular diagnostics, targeted therapies and personalized medicines.
Discipline: Applied Medical Sciences, Westmead
PROJECT 3. Can proteomic analysis of scarlessly collected samples discriminate between eczema, psoriasis and actinic keratosis?
Primary supervisor: Prof. Pablo Fernandez Penas
Co-supervisor: Dr Ali Azimi
Eczema, psoriasis and actinic keratosis are different skin lesions. Currently, physical examination of the lesions by naked eye or with the assistance of imaging technologies such as dermoscopy are the main approach in diagnosing these lesions. However, these lesions may sometimes be mistaken for one another specially when they present with similar clinical features and appearances. Any misdiagnosis or delayed diagnosis will have undesired consequences for the patients. Currently, there are no validated biomarkers to complement the conventional diagnoses. In this project we propose using non-invasive patient sample collection, tape-stripping, coupled with state-of-the-art mass-spectrometry-based proteomic technique to identify lesion-specific protein biomarkers for improved diagnosis of these lesions. Subsequently, this may aid in the development of targeted therapies and personalized medicines.
Discipline: Applied Medical Sciences, Westmead
PROJECT 4. Imaging and Proteomic Analysis of Early Melanoma; A Pilot Study
Primary supervisor: Prof. Pablo Fernandez Penas
Co-supervisor: Dr Ali Azimi
Australia has the second highest melanoma rates in the world (after New Zealand), and melanoma represents a huge burden to the Australian health system with treatment costs alone surpassing $201 million annually. This figure is expected to grow substantially with the expansion of new therapies for late-stage disease. Melanomas may progress from non-life-threatening pigmented lesions to minimally invasive melanoma and eventually to deadly disease in open sight. Detection of pre- or early melanoma lesions is expected to save lives, to reduce morbidity and costs associated with treatment of late-stage disease, and to reduce the high socio-demographic inequalities in melanoma outcomes
Currently, non-invasive imaging technologies such as confocal imaging and sequential digital dermoscopic are used to observe change in pigmented lesions over time. Suspected lesions are subsequently excised to undergo histopathologic analysis to rule out skin cancer.
The field of cancer research is rapidly moving towards the discovery of molecular signatures using proteomic technique. Proteomics allows a comprehensive examination of protein content of cancer samples, leading to the identification of lesion-specific molecular signatures.
In this project we will combine imaging data with proteomics technique to study early melanoma samples. We will first collect imaging data from patients with early melanoma. This will be followed by collecting patient samples from the surface of the skin (stratum corneum) using a non-invasive tape-stripping method. Proteomic analysis will be performed on the samples, and its findings will be corelated with the imaging data. This will help us with a better understanding of disease mechanisms while aiding the development of non-invasive molecular diagnostics.
Discipline: Applied Medical Sciences, Westmead
PROJECT 5. Comparison, validation and characterisation of primary human cutaneous squamous call carcinoma cells (cSCC) isolated and cultured using different techniques
Primary supervisor: Prof. Pablo Fernandez Penas
Co-supervisor: Dr Ali Azimi
Co-supervisor: Dr Minal Dalvi or Dr Emily Fuller
cSCC is a common skin cancer with malignant potential, the highest incidence of which occurs in Australia. Understanding of the development pathways resulting in invasive cSCC is lacking. Previous work in this group has highlighted differentially expressed proteins in cSCC compared to adjacent normal tissues, which could potentially be targets for interruption of disease progression and therefore early treatment targets.
Cell or tissue culture is often the first means of creating a representative disease model. Obtaining cells of interest and establishing primary culture is essential, as well as characterisation of the model. This project will involve collection of cSCC tissue (of different grades) and adjacent normal tissue samples from consented patients undergoing surgical treatment. Specific aims of the project are to investigate two different methods of establishing cell culture; using enzymatic digestion of tissue and comparing this will explant/cell outgrowth. Once cells are established, validation and characterisation studies will include viability and proliferation assays, morphology assessment, immunocytochemistry assays, western blot and molecular characterisation. The profile of primary cSCC cells of different grades will be compared to primary cells derived from adjacent normal tissues as well as to that of commercially available relevant cell lines.
Discipline: Applied Medical Sciences, Westmead
PROJECT 6. Investigating the role of NECTIN2 in cutaneous squamous cell carcinogenesis
Primary supervisor: Prof. Pablo Fernandez Penas
Co-supervisor: Dr Minal Dalvi
Co-supervisor: Dr Ali Azimi
Cutaneous squamous cell carcinoma (cSCC) is a common non-melanoma skin cancer (NMSC) with high prevalence rate globally. It accounts for 20% of all NMSC cases in Australia. Cutaneous cSCC may develop from premalignant actinic keratosis and Bowen’s disease, and they exhibit overlapping clinical and histopathological behaviours. The molecular mechanisms behind the development of cSCC is unknown.
Our recent proteomic investigation of formalin-fixed and paraffin embedded samples has shown that the protein, NECTIN2, is highly regulated in cSCC lesions. The role of NECTIN2 in cell differentiation, proliferation and survival is well established, and its increased expression has been described in advanced and metastatic breast cancer and oesophageal SCCs. These findings provide a basis for further investigation into the utility of NECTIN2 as a SCC biomarker as well as its role in cSCC carcinogenesis. The present study will evaluate the role of NECTIN2 in cSCC carcinogenesis firstly by knocking down the NECTINC2 gene in cSCC cell lines using siRNA gene knockdown. Subsequently, the effect of NECTIN2 gene knockdown in cell proliferation and migration will be evaluated using xCelligence Real Time Cell Analysis Systems, and the findings will be compared with the healthy control cell lines. The findings of this study will be significant as it will likely provide evidence on the role of NECIN2 in cSCC carcinogenesis, its value as diagnostic biomarker and a potential therapeutic target.
Discipline: Applied Medical Sciences, Westmead
PROJECT 7. Integrative proteomic and genomic analysis of early melanoma lesions
Primary supervisor: Prof. Pablo Fernandez Penas
Co-supervisor: Dr Ali Azimi
Australia has the second highest melanoma rates in the world (after New Zealand), and melanoma represents a huge burden to the Australian health system with treatment costs alone surpassing $201 million annually. This figure is expected to grow substantially with the expansion of new therapies for late-stage disease. Melanomas may progress from non-life-threatening pigmented lesions to minimally invasive melanoma and eventually to deadly disease in open sight. Detection of pre- or early melanoma lesions is expected to save lives, to reduce morbidity and costs associated with treatment of late-stage disease, and to reduce the high socio-demographic inequalities in melanoma outcomes.
The integration of proteomics with genomics and transcriptomics, termed as proteogenomics, is an emerging approach that promises to advance basic, translational and clinical research. By combining genomic and proteomic information, new insights can be gained due to a more complete and unified understanding of complex biological processes.
In this project, using various bioinformatics tool, we will analyse and integrate informative features from the already collected proteomic (inhouse) and genomic (obtained from repositories) data from early melanoma lesions. This will help us with a better understanding of the disease mechanisms and will also provide evidence on the value of a combination of genes and proteins as diagnostic biomarker and a potential therapeutic target.
Discipline: Applied Medical Sciences, Westmead