2018 Abstracts

Tason Turek, Dixie State University

Somer Doody, Utah Valley University

Kaden Jordan, Dixie State University

Christian Kodele, Lian Li, Jane Yang, University of Utah Non-Hodgkin lymphoma (NHL) is an immune disease mostly of B-cell origin (eighty-five percent of the time) as well as the ninth leading cause of cancer death in the United States. Although treatments for NHLs greatly improved following the FDA approval of Rituximab (RTX), refractive malignancies still occur that are nonresponsive and/or resistance to current therapies in at least a third of all patients. This has been attributed both to the inability of immune effector cells (eg., macrophages, natural killer cells) to hypercrosslink ligated monoclonal antibodies (mAbs), and to Fc receptor (FcR)-mediated endocytosis or ‰ÛÏtrogocytosis‰Û of CD20 antigens. In order to address these clinical obstacles, we designed a novel paradigm in macromolecular therapeutics that can specifically kill cancer cells without a drug. This paradigm is based on the use of anti-CD20 Fab’ fragments in a multivalent system. Crosslinking of CD20 receptors leads to receptor clustering, transfer to lipid rafts, opening of a calcium channel, and ultimately apoptosis. Additionally, the removal of the Fc fragment resulted enticingly in both the rendering of the system to be immune dependent and in decreasing the numerous adverse effects. In this study, we have used human serum albumin (HSA) as the multivalent carrier of RTX based Fab’ fragments. We have covalently attached multiple Fab’ fragments to HSA, characterized the nanoconjugate’s physiochemical properties, and evaluated its efficacy to induce apoptosis of Raji B cells in vitro. The efficacy of the nanoconjugate to induce apoptosis was determined with Annexin V assay and flow cytometry. The interaction of the nanoconstruct with Raji cells was characterized using confocal microscopy of Cy5 labeled conjugates. As predicted, the HSA-(Fab’)x conjugate was able to induce cell death in vitro. The results of the Annexin V apoptosis assay showed that 38.9 percent of the cell population treated with the conjugate became apoptotic, while 13.6 and 15.7 percent of the cell populations untreated and treated with whole RTX mAb became apoptotic respectively. Furthermore, images recorded by use of confocal microscopy suggest that the attachment of HSA-(Fab’)x conjugate to the cell membrane is CD20 specific. While not conclusive, the combination of these results suggest that the mechanism of action involves cross-linking of the CD20 receptor, which subsequently induces apoptosis. We believe these results warrant further investigation of the mechanism of action of HSA-(Fab’)x, as well as the treatment potential of this nanoconjugate.

Lydia Morley, University of Utah

Joshua Wilkerson; Seung-Ook Yang; Parker J. Funk; Steven K. Stanley, Brigham Young University

Tegan Parks, Utah Valley University

Mason Smith, Southern Utah University

Diabetes affects over 30 million Americans and 185,000 Utahn’s. Type 1 and Type 2 diabetes are characterized by decreased functional β-cell mass and insulin production. Diabetes also results in increased circulating glucose and fatty acid levels, which damage and destroy β-cells over time. Our study will shed further light on the effects of palmitate, the most commonly made fatty acid in the liver, on hyperlipidemia. In this study we test the specific effects of chronic palmitate exposure on various cell lines acclimated to 0.15 mM, 0.3 mM, and 0.5 mM concentrations of palmitate. We demonstrate the effects of progressive long-term exposure to palmitate on β-cell proliferation and resistance to apoptosis. We demonstrate mechanistic changes that result in the observed phenotypes. Our goal in this study is to explore how β-cells adapt to exposure to hyperlipidemia, and to define interventions to protect β-cells from the harmful effects of hyperlipidemia.

Jacob Delano; Nicholas Brian, Utah Valley University

Ashley Wiltsie, University of Utah

Aaron Leifer, Jasmine Banner, Collin Christensen, Trevor Lloyd, Kenneth Call, Brigham Young University Diabetes Mellitus has become a worldwide epidemic affecting over 400 million people. Both type 1 and type 2 diabetes result from the body’s inability to produce or respond to insulin in order to regulate blood sugar. In both cases, the insulin secreting ë_-cells in the pancreatic Islets of Langerhans have become endangered and in many cases non-functional. The function of these ë_-cells is defined by their ability to multiply and maintain a steady number, to defend against induced cell death and ultimately to secrete insulin. Since ë_-cell production reaches its peak during fetal development, this would suggest that diabetics have an inactive pathway to produce functional ë_-cells. However, recent studies have identified key transcription factors that aid pancreatic progenitors in becoming functional ë_-cells. Pdx1 is a transcription factor that is active throughout the ë_-cell pathway and found in mature ë_-cells. Research has identified Pdx1 as a key component in helping both ë±-cells and ë_-cells proliferate and even in reprogramming ë±-cells to become functional ë_-cells. Additionally, Pdx1 has been identified to help ë_-cells effectively secrete insulin. We present data demonstrating the effect of Pdx1 adenoviral over-expression on three independent markers of functional ë_-cell mass: 1) cell proliferation, 2) cell survival, and 3) insulin content and secretion. Defining the effect of Pdx1 on each of these parameters will provide further data to explore therapeutic interventions for diabetic patients.

Karaleen Anderson; Mariel Hatch, Utah Valley University

Parker Booren, Nathanael Jensen, Talon Aitken, Samuel Grover, Jackie Crabree, Brigham Young University Diabetes continues to grow at a rapid rate, affecting the lives of both young and old. Both Type 1 and Type 2 diabetes lead to eventual ë_ cell depletion (and subsequent decrease in insulin secretion). This can be treated through ë_ cell transplantation from the pancreata of cadavers. Currently, collecting sufficient ë_ cells for one diabetic patient requires pancreata from multiple cadavers. If proliferation can be induced in a donor’s aged ë_ cells, transplantation would become more effective as one donor now becomes sufficient to serve one or two patients. Nkx6.1 is a transcription factor that increases insulin secretion and induces proliferation of young rat ë_ cells (5 weeks) through the upregulation of its target genes: VGF, Nr4a1 and Nr4a3. Aged rat ë_ cells (5+ months) fail to proliferate after overexpression of Nkx6.1. We have also shown that upregulation of Nkx6.1’s target genes is disrupted in these aged ë_ cells. This may be due to changes in expression of a binding partner necessary for Nkx6.1’s upregulation of these target genes or to changes in Nkx6.1 posttranslational modifications that impede binding partner interactions in aged ë_ cells. We present data from co-immunoprecipitation and mass spectrometry experiments that reveal the presence or absence of Nkx6.1’s binding partner in young and aged ë_ cells. Furthermore, we present mass spectrometry results of Nkx6.1 posttranslational modification from young and old ë_ cells. This data will increase understanding on the ability of Nkx6.1 to upregulate its target genes in an aged ë_ cell.

Colton Smith, Dixie State University

Kayleigh Ingersoll, Brigham Young University

Nayla Rhein, Southern Utah University

Trevor Lloyd; Mason Poffenbarger; Austin Ricks; Andrew Barlow; Zoey Fishburn, Brigham Young University

Alyson DeNittis, Utah Valley University

Ariel Green; Taylor Schroedter, Brigham Young University

Mary Rosbach, Brigham Young University

Jayson Foster, Dixie State University

Austin Bettridge, Utah Valley University

Nathanael Nelson, Brigham Young University

Ben Thrift, Southern Utah University

Autumn Wyatt, Dixie State University

Trenton Colton; David Fullwood, Brigham Young University

Joseph Millar, Utah Valley University

Anastasiia Matkovska; Austin Bettridge; Blake Allred; Jeff Keller, Utah Valley University

Jackson Podis, Westminster College In the Guna Yala archipelago, PanamÌÁ, the removal of coral species for construction of coral walls has been a common practice for the Guna Yala indigenous group. This practice has the potential to drastically alter the community structure of offshore reefs. This study analyzed three reefs offshore of islands with varying coral wall volumes to quantify macroalgae and scleractinian coral cover, diversity of scleractinian coral species, and correlation between macroalgae and scleractinian coral cover. All three study sites exhibited significant differences in scleractinian coral coverage; a significant negative correlation was shown between scleractinian coral cover and macroalgal cover, and the site with the largest coral wall volume showed the lowest rates of coral species commonly used for mining. These results are telling of the potential effects coral mining can have on coral reefs in the Guna Yala archipelago, and aim to inform the development of marine resource management plans in the future.

Thomas Shober; Jaxon Roller; Ashley Kennedy, University of Utah

Joseph Rich, Brigham Young University

Chase Omana, University of Utah

Konstantinos Karpos; Koren Roach, University of Utah

Kyle Hakes; Heather Erickson, Brigham Young University

Katherine Safsten, Brigham Young University

Kathleen Fotheringham, Southern Utah University

Keanna Graff, Dixie State University

Maggie Marchant, Brigham Young University

Dakota Halley; Stephanie Johnstone; Andrea Deever; Cassidie Medina; Kimberly Child, Dixie State University

Mark Albrecht; Kristin Wilson-Grimes; Sennai Habtes, Southern Utah University

Jonathan Jacobs, Brigham Young University

Edgar Judd, Southern Utah University

Sydnee Higginson, Brigham Young University

Chad Talbot, Utah Valley University

Catherine Miner, Utah State University

Frost Mitchell, Utah State University

Jessie Byers, Southern Utah University

Peyton Carter, Southern Utah University

Tyler Hole, Weber State University