Position title: Exploring Cutaneous Squamous Cell Carcinoma (cSCC) using integrated multi-omics approaches

Employer: University of Wollongong

Closing date: 30 december 2021

Brief position description: Exploring the mutational landscape of Cutaneous Squamous Cell
Carcinoma (cSCC) using integrated multi-omics approaches.

Our group is working to decipher the driver mutations and molecular pathways that promote metastasis in cSCC using a multi-Omics (whole genome/transcriptome/methylome) approach. This information will also be used to facilitate the stratification of potential clinically important genes (biomarkers) as predictors of metastatic potential in primary cSCC and identify potential new therapeutic targets. This PhD project will provide the opportunity for a student to work on the integration and analysis of the multi-omics dataset being generated by the group. The student will join a collaborative team of clinicians and molecular and bioinformatics scientists exploring cSCC from the Illawarra Health and Medical Research Institute (located on the University of Wollongong campus), the Sydney Head Neck Cancer Institute and at the National Cancer Centre Singapore Scholarship Information

A PhD scholarship is available for commencement at the University of Wollongong, Australia.

Stipend: $28,597* non-taxable (maximum 3 years full time). Part-funded by Cancer Institute NSW, Translational Program Grant 2020/TPG2081

Entry Requirements

Outstanding applicants holding First Class Honours or a Master’s degree in a discipline relevant to the research topic such as bioinformatics and biostatistics, genomics or genetics, and an interest in cancer biology are encouraged to apply. Experience with programming skills such as R statistical language and working in a UNIX environment is required. Bash scripting, additional programming skills such as perl, python, C++ would be a plus. Next generation sequencing related knowledge such as file formats, alignment tools/methods, or basic bioinformatics algorithm knowledge would also be advantageous. Applicants must remain enrolled as a full-time PhD student of Faculty of Science Medicine and Health, University of Wollongong for the duration of this scholarship.

Applicants will be enrolled in the Faculty of Science Medicine and Health, University of Wollongong and are expected to commit to full-time study based at the Illawarra Health and Medical Research Institute located on the UOW campus.

Scholarship open to domestic and international applicants but must be available to start in early 2022 at UOW.

Supervisors/collaborators

Prof Marie Ranson, Cancer Cell and Molecular Biology Group leader,
Theme Leader Diagnostics and Therapeutics, Illawarra Health and Medical Research Institute (IHMRI)
School of Chemistry and Molecular Bioscience, Molecular Horizons, UOW, and IHMRI,

A/Prof Bruce Ashford,
Head and Neck Surgeon, IHMRI Clinical Director, School of Medicine/IHMRI/ISLHD

Dr Amarinder Thind; Bioinformatician, cSCC Group
School of Medicine/IHMRI

Prof Jonathan Clark; Head and Neck Surgeon, Director of Head and Neck Research
TPG lead, Chris O'Brien Lifehouse Centre, Camperdown, Sydney

HOW TO APPLY

Applicants are encouraged to contact Prof Marie Ranson (mranson@uow.edu.au) or A/Prof. Bruce Ashford (bgashford@gmail.com) with an Expression of Interest (EOI). The EOI should include: (1) CV clearly outlining education qualifications with GPA, research and work experiences, (2) copies of academic transcripts, and (3) list of publications
(if any).

Proposal background

The non-melanoma skin cancer cutaneous squamous cell carcinoma
(cSCC) is one of the most common malignancies in Australia and is a
major health resource burden (Ashford et al 2017). Excessive exposure to
ultraviolet (UV) radiation, which causes cumulative DNA damage, is the
primary risk factor (Ashford et al 2017). Metastases to regional lymph
nodes occur in 2-5% of cases and impart a significant risk of morbidity and
mortality. Standard treatment for these metastases involves a
combination of radical surgery and radiation treatment which profoundly
reduces patient’s quality of life. There are no standardised
chemotherapeutic regimens and radiotherapy can stimulate aggressive
recurrence. Our group is attempting to decipher the driver mutations and
molecular pathways that promote metastasis in cSCC. This will facilitate
the stratification of potential clinically important genes (biomarkers) as
predictors of metastatic potential in primary cSCC and identify potential
new therapeutic targets. We have already completed the largest cohort of
metastatic cSCC whole genome sequencing (WGS). WGS has allowed us to
describe UV-induced mutation patterns that persist in metastases of cSCC
and excessively affect insulator binding sites. Recurrent patterns of
variation in key regulatory elements, and recurrent copy number and short variation in cancer-associated genes were also found (Mueller et al
2019; Ashford et al submitted).
We are currently extending our WGS and completing RNA sequencing and
methylome analysis across the clinicopathologic spectrum of cSCC
including metastasising and non-metastasising primary tumours and their
coincident metastases. This PhD project will provide the student the
opportunity to work with our team of clinicians and molecular and
bioinformatics scientists to explore cSCC disease by integrating the cSCC
related data obtained from our multi-Omics (whole
genome/transcriptome/methylome) approach. We hope to use these
sophisticated methods to better understand the biology of cSCC and to
identify candidate genes as discriminating biomarkers of metastasis in
cSCC; ie a potential prognostic “gene signature” that distinguishes
primary tumours with potential to metastasize from those with
clinicopatholigical “high risk” features but without metastatic potential.
Findings from these analyses can then also be employed in functional
genomic analyses and drug response profiling in cSCC patient-derived
cultures established in the Ranson lab (Perry et al 2020).

REFERENCES

Ashford, BG, Clark, J, Gupta, R, Iyer, NG, Yu, B, Ranson, M (2017)
Reviewing the genetic alterations in high-risk cutaneous squamous cell
carcinoma: A search for prognostic markers and therapeutic targets. Head
and Neck 39, 1462-1469. doi: 10.1002/hed.24765
Mueller SA, et al (2019) Mutational Patterns in Metastatic Cutaneous
Squamous Cell Carcinoma. Journal of Investigative Dermatology (2019)
139, 1449e1458; doi:10.1016/j.jid.2019.01.008.
Perry J, Ashford B, Thind AS, Gauthier ME, Minaei E, Major G, Iyer NG,
Gupta R, Clark J, Ranson M. (2020) Comprehensive Mutational and
Phenotypic Characterization of New Metastatic Cutaneous Squamous Cell
Carcinoma Cell Lines Reveal Novel Drug Susceptibilities. Int J Mol Sci.
21(24):9536. doi: 10.3390/ijms21249536.
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Job website:

Contact name: Marie Ranson

Contact email: mranson@uow.edu.au