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Sarah Miles

Sarah Miles, PhD 
Assistant Research Professor

Research Interests

My main research involves the use of dietary constituents to inhibit the growth and progression of cancer, and elucidating the molecular mechanisms and pathways involved in malignant progression and chemotherapeutic resistance.  My early studies involved the use of ascorbic acid (vitamin C) to inhibit the progression of melanoma and potentially augment chemotherapeutic response by enhancing regulation of the Hypoxia Inducible Factor 1 alpha (HIF1-a) transcription factor. HIF-1α has been implicated as a key player in the development and progression of melanoma as well as several other cancer types. Tumor tissues of various types have been found to be ascorbate depleted when compared to normal surrounding tissue, and in conjunction, often expressed elevated levels of HIF-1α. My lab has documented the ability of physiological concentrations of ascorbic acid to reduce both the protein expression and activity of HIF-1α and subsequently inhibit the invasive potential of metastatic melanoma cells. These findings provide evidence that ascorbate, as a critical cofactor for prolyl- and asparginyl-hydroxylase enzymes (PHD and FIH), which regulate the stability and transcriptional activity of HIF1-a, may play an important role in the regulation of aberrant expression and activity of HIF-1α in melanoma cells. By documenting evidence for the efficacy of ascorbic to impede an aggressive malignant phenotype, this work can potentially change the traditional course of therapy for individuals with melanoma or other cancer types with aberrant HIF-1α. I am also interested in the use of other natural compounds (capsaicinoids) and phytochemicals (quercetin) as adjuvant or potentially preventative cancer therapy. Presently, I am involved in investigating the use of these compounds in lung and ovarian cancer, which have a higher prevalence in the Appalachian region (compared to melanoma), allowing more opportunity to translate the use of natural compounds to improve the clinical outcomes of cancer patients.