Carlos Smith Diaz Email and Phone Number

As a civil litigation solicitor I work on a wide range of matters including construction disputes, contractual disputes, property disputes, misrepresentation cases, challenges to estates, debt collection, liquidation and sports law.

Cutaneous melanoma is a highly invasive, heterogeneous and treatment resistant cancer. It’s ability to dynamically shift between transcriptional states or phenotypes results in an adaptive cell plasticity that may drive cancer cell invasion or the development of therapy resistance. The expression of peroxidasin (PXDN), an extracellular matrix peroxidase, has been proposed to be associated with the invasive metastatic melanoma phenotype. I have been involved in analysing the transcriptomes of New Zealand metastatic melanoma (NZM) cell lines characterised by either high or low PXDN expression. In doing so, I unearthed a strong association between high PXDN expression and the undifferentiated invasive melanoma phenotype. I further observed that PXDN knockout in a high PXDN expressing cell line decreased the expression of epithelial-mesenchymal transition and invasive marker genes. This research provides compelling evidence that PXDN plays a functional role in melanoma invasion by promoting an invasive, mesenchymal-like transcriptional phenotype.

PhD in Epigenetics, Biochemistry and BioinformaticsThesis title: "Vitamin C and TET-Mediated Demethylation in Leukaemia and Development"Humans rely on dietary intake to maintain body levels of vitamin C, a molecule that is critically important for the activity of the epigenetic TET (Ten-Eleven Translocase) enzymes. The TETs catalyse the oxidation of 5-methylcytosine in DNA and regulate gene expression.My PhD shows that vitamin C stimulates TET activity and results in transcriptional changes in leukaemia cells. Further, restricted vitamin C intake during guinea pig pregnancy resulted in epigenomic alterations in offspring that were detectable at birth and persisted throughout the lifetime of the animal. The findings reveal that vitamin C deficiency due to poor diet, a common issue in our society, disrupts the TET-driven regulation of methylation, potentially altering lifelong biological and health outcomes in individuals and their children.During my PhD I developed extensive expertise in the analysis of transcriptomics (RNAseq) data from cultured cells and tissue samples, including quality control, mapping, differential gene expression analysis, pathway analysis and data visualisation. Additionally, I performed an extensive analysis of bisulphite sequencing data (RRBS, oxRRBS and WGBS) to measure changes in CpG island methylation.

BBiomedSc (Hons) Thesis: "Vitamin C as an Epigenetic Therapeutic for Acute Myeloid Leukaemia"Acute myeloid leukaemia (AML) is a deadly disease characterised by the abnormal proliferation of immature blood cells in the bone marrow with a block in haematopoietic differentiation. I examined the epigenetic effects of vitamin C in AML, by using a SKM-1 myeloid leukaemia cell model characterised by a heterozygous loss-of-function mutation in TET2. My research shows that vitamin C can act via at least two separate mechanisms to decrease the proliferation of leukaemia cells in vitro. One mechanism likely involves the generation of hydrogen peroxide causing cell death. The second mechanism was independent of hydrogen peroxide and caused decreased cellular proliferation.

At Lane Neave, I worked as a solicitor in the building and construction law team. I was involved in drafting and advising on construction contracts and civil litigation relating to building disputes.