Projects
PhD/Honours Students:
Understanding the role of the underlying dermis in the genesis and progression of basal cell carcinoma
Basal cell carcinoma is the most frequent malignancy in the world. It affects almost 1/3 Australian by the age of 70. Despite being a highly common tumour it does not metastasize and grows locally. Biologically it has many features of hair follicles and relies on a highly specialized underlying mesenchyme. In recent years we have identified the underlying mesenchyme driving hair follicle regeneration/tumour formation and have worked out means to isolate and culture these specialised cells effectively maintaining their hair regeneration capacity. The objective of the present study is to identify the key pathways involved in this mesenchymal epidermal interaction to find potential molecular targets for intervention.
Study of epidermal clonal progression towards cancer.
Skin cancer is the most prevalent form of malignancy. The main environmental factor driving skin cancer is ultraviolet irradiation. It is known that upon UVR cells accumulate mutations that will eventually give rise to cancer. However the efficiency and progression of this process is not known. We will here use mouse genetic models to label individual keratinocytes with different colours to follow their fate over time through confocal or biphoton microscopy in situations with or without UVR. Upon understanding clonal proliferation in response to UVR we will examine the rate of mutations within individual clones affected or not by p53 mutations using laser capture microdissection and genome sequencing. This will provide an unprecedented view on clonal progression towards cancer.
Tumour heterogeneity towards metastasis.
Tumours are composed of various subclones with different invasive and proliferative properties. The goal of this study is to identify gene expression signatures associated with invasive properties within subclones of the same tumour. We will use Rainbow technology to label tumour cells individually and follow the formation of subclones and follow their progression towards metastasis. Comparing subclones that have metastasized to those that have not metastasized will inform on the tumour genes required for this process.
MPhil Students:
To understand differences between basal cell carcinoma subtypes at the genomic, transcriptomic and proteomic level
Reccurrence rates of BCCs depend essentially on their subtype. The objective is to collect primary BCC tumours and compare nodular BCC to fibrosing and micronodular subtypes using RNA and DNA sequencing as well as validating targets on tissue arrays.
About me
Professor Khosrotehrani is a clinical scientist interested in skin biology, regenerative medicine and skin cancer.
He was recently appointed at the University of Queensland Centre for Clinical Research (UQCCR) and the newly established Translational Research Institute in Brisbane, Australia. Dr Khosrotehrani obtained his MD from the Cochin-Port Royal School of Medicine at René Descartes University, Paris, France, specialized in Dermatology and a fellow of the Australasian College of Dermatologists.
He is also a former graduate of the Ecole Normale Supérieure and the Institut Pasteur of Paris (Université Paris VI, Pierre et Marie Curie) where he obtained a PhD in Physiology and Physiopathology. During his post-doctoral training at Tufts-New England Medical Center, Boston, USA, Dr. Khosrotehrani helped establish the contribution of pregnancy-associated stem cells to tissue repair by demonstrating their multipotent capacity with a specific potency towards the endothelial lineage. The originality of this work was recently acknowledged by the NHMRC through an achievement award (2011) and he is currently an NHMRC Career Development Fellow.
The main focus of his laboratory, the Experimental Dermatology Group, is on mesenchymal-epidermal interactions in stem cell maintenance and cancer. His research has broad applications in skin wound healing, regenerative medicine and cancer initiation and progression.
