Dr.Kathryn Leyva, Ph.D.

Research Summary

My research focuses in three main areas: 1. Examining the role of miRNA in the epigenetic regulation of cancer. 2. Understanding the mechanisms involved in epigenetic regulation of EMT in cancer, and 3. The relationship between progranulin and lysosomal function in cancer and neurodegenerative disease.

Project #1: Role of miRNA in cancer progression

Our research in this area focuses on the role of miRNA in cancer development. miRNAs have been shown to be involved in epigenetic regulation and promotion of oncogenesis in various cancers. Specifically, we are interested in determining if miRNAs promote oncogenesis in normal cells by suppressing the immune response to tumor cells and accelerating the process of EMT (epithelial to mesenchymal transition), a component of the metastatic process. Our lab is currently focused in examining the miRNA expression profile of patient-derived cutaneous squamous cell carcinoma (cSCC) cells and determining how these miRNA may be influencing the oncogenic potential of keratinocytes.

Project #2: Epigenetic regulation of EMT in cancer cells

The second focus of the laboratory involves examination of epigenetic regulatory mechanisms in cancer. It is postulated that epigenetic modifications within cancer cells can negatively impact effectiveness of treatment and understanding how these modifications are regulated or controlled is clinically important. Two of the epigenetic mechanisms that we have focused on are miRNAs and acetylation of histones and p53 using both cancer cell lines and patient-derived tissues, allowing us to investigate these epigenetic factors on EMT and oncogenic potential. 

Project #3: Relationship between progranulin and lysosomal function in cancer and neurodegenerative disease 

Most recently, our lab has shifted to determine the relationship between lysosomal pH and progranulin processing using the epigenetically plastic SW13 cell line, in which progranulin was first discovered. Preliminary data from our lab have shown that lysosomal pH differs in the two cellular subtypes, and that progranulin may also be differentially processed, resulting in the production of varied granulin subunits in each subtype. Collectively, altered lysosomal function and/or differential progranulin processing must be influencing cellular behavior differently between the two subtypes. These results have led our laboratory to begin examining the relationship between progranulin, lysosomal function, and neuroinflammation that may pave the way to developing novel therapeutics targeting the early stages of disease.