Kathryn J. Leyva, Ph.D.

Professor


Education:

1990  B.S. Biology  University of Oregon
1992  M.S. Biology  University of Oregon
1996  Ph.D. Biological Sciences  Northern Arizona University

Contact information:

Department of Microbiology & Immunology
Arizona College of Osteopathic Medicine
19555 N. 59th Avenue
Glendale, AZ 85308

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 regulation of cellular motility, and 3. Isolation and characterization of halophilic microorganisms and halocins.

Project #1: Exosomes and miRNAs in cancerCutaneous SCC

Our research in this area focuses on the role of exosomes and miRNA in cancer development. Exosomes are microscopic vesicles that are involved in cell-to-cell communication. These exosomes contain a variety of mRNA, miRNA and proteins that have shown to be involved in epigenetic regulation and promotion of oncogenesis in various cancers.  Specifically, exosomal contents have been shown to 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 (see image, right) and determining how these miRNA may be influencing the oncogenic potential of keratinocytes.

Project #2: Factors influencing cellular migration and EMT

Our lab has been interested in the factors that influence the collective migration of zebrafish keratocytes and the process of epithelial to mesenchymal transition (EMT). We have shown EMT occurs over a 7-day period in zebrafish explant cultures, as demonstrated by changes in morphology and cadherin expression (see figure below).  Our current focus is on matrix metalloproteinases (MMPs). Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that function to degrade extracellular matrix proteins, cleave cytokines to alter their activity, and cause ectodomain shedding of cell surface molecules to alter cellular responses. Much of the literature on MMPs and migration show MMPs have a promigratory effect.  In our lab, we have shown that MMP2, MMP9 and MMP14 all have a promigratory effect while MMP13 plays an antimigratory role in our system.  Therefore, we are interested in examining this complex interplay among these four MMPs in controlling migration of keratocytes.

EMT

Project #3:  Isolation and characterization of halophilic microorganisms and halocins

Production of protein antibiotics is a near universal feature of all living things; proteinaceous antibiotics have been found in the spectrum of living forms, including bacteria, plants, protozoans, insects, crustaceans, amphibians, and humans.  Halocins are proteinaceous antibiotics produced by halophilic (salt-loving) members of the prokaryotic Domain Archaea.  In comparison to the hundreds of protein antibiotics that have been characterized in the Domains Bacteria and Eukarya, only a few halocins have been characterized or partially characterized, and the number of halophilic Archaea are also vastly underrepresented in the literature.  My specific projects are two-fold: to characterize the diversity, abundance, and distribution of halophilic microorganisms in White Sands National Monument and to identify, purify, and characterize any antimicrobial peptides or proteins produced.  These organisms can theoretically be a source of novel antimicrobial compounds that can be of clinical interest.

Selected Publications:

Belden SE, Uppalapati CK, Pascual AS, Montgomery MR, Leyva KJ, Hull EE, Averitte RL. Establishment of a clinic-based biorepository. Journal of Visualized Experiments, in review.

Hull EE, Montgomery MR, Leyva KJ (2016). HDAC inhibitors as epigenetic regulators of the immune system: Impacts on cancer therapy and inflammatory diseases. BioMed Research International, 2016:8797206 doi:10.1155/2016/8797206.

Davis MR, Daggett JJ, Pascual AS, Lam JM, Leyva KJ, Cooper KE, Hull EE (2016). Epigenetically maintained SW13+ and SW13- subtypes have different oncogenic potential and convert with HDAC1 inhibition. BMC Cancer, 16:316 doi:10.1186/s12885-016-2353-7.

Rapanan JL, Pascual AS, Uppalapati CK, Cooper KE, Leyva KJ, Hull EE (2015). Zebrafish Keratocyte Explants to Study Collective Cell Migration and Reepithelialization in Cutaneous Wound Healing. Journal of Visualized Experiments (96), e52489, doi:10.3791/52489.     

Rapanan JL, Cooper KE, Leyva KJ, Hull EE (2014). Collective cell migration of primary zebrafish keratocytes. Experimental Cell Research 326(1):155.

McDonald T, Sumner A, Reyes J, Pascual A, Uppalapati C, Cooper K, Leyva K, Hull EE (2013). Matrix Metalloproteinases & Collective Cell Migration in 24 hour Primary Zebrafish Explant Cultures: MMP13 Plays an Inhibitory Role & MMP14 May Respond to Stretch. Cell Biology International Reports 20(2):24. 

McDonald T, Pascual A, Uppalapati C, Cooper K, Leyva K, Hull EE (2013).  Zebrafish keratocyte explant cultures as a wound healing model system: differential gene expression & morphological changes support epithelial-mesenchymal transition. Experimental Cell Research 319(12):1815.

Shand RF and Leyva KJ (2008). Chapter 11: Archaeal Antimicrobials: An Undiscovered Country, pp. 233-243. In: Archaea: New Models for Prokaryotic Biology, ed. P. Blum. Horizon Press.

Shand RF and Leyva KJ (2007). Chapter 5: Peptide and Protein Antibiotics from the Domain Archaea: Halocins and Sulfolobicins, pp. 93-109. In: Bacteriocins - Ecology and Evolution, eds. M.A. Riley and M. Chavan. Springer-Verlag Publishing Co.