Positions

Overview

  • My overarching research goal is to understand how dysfunctional sphingolipid metabolism contributes to the development and progression of diseases such as acute myeloid leukemia (AML). I am particularly interested in utilizing this knowledge to discover and develop experimental therapeutic modalities that manipulate these biologically relevant pathways. In order to facilitate my goals as a researcher, I have divided my research into two categories: 1) sphingolipid and NADPH oxidase biology in leukemia, and 2) experimental therapeutics and nanomedicine. In order to address these areas I have developed a translational research program that utilizes state-of-the-art animal models to characterize the pathobiology of disease as well to engage in effective preclinical experimental therapeutic testing. By understanding how sphingolipid biology varies in the pathobiology of leukemia, we can initiate drug discovery processes, including from natural products, to identify and optimize new therapeutically active molecules.


    It is a primary goal of my lab's research to apply the knowledge gained from mechanistic biological studies to the development and testing of translational experimental therapeutics. There is a particular interest in chemical library and natural product screening, as well as in the development of nanodelivery systems for drug delivery. Our research team has adapted bioassays for screening approaches which target different aspects of AML pathobiology. In this way, chemical libraries have been screened for compounds that enhance nanoliposomal ceramide (e.g. 7,8-benzoflavone), and which have subsequently been formulated into nanoliposomes to enhance in vivo therapeutic efficacy. Likewise, our research team has employed these assays in coordination with chemist colleagues through a natural products fractionation process with the goal of identifying novel therapeutics. One example has been the evaluation of Oplopanax horridus (Devil’s club), which is a plant native to Alaska and the Pacific Northwest that is used in traditional indigenous medicine. Using bioassay-directed approaches, extracts and refined fractions have been identified with potent anti-AML activity. In vivo efficacy of extracts has been further evaluated using immunodeficient mice engrafted with human AML. Improvements to the therapeutics identified through these natural products and chemical library screening efforts occurs primarily by formulating them into nanodelivery systems. Fundamentally, our research with nanotechnologies seeks to improve the ability to deliver therapeutic molecules to target cells while simultaneously decreasing systemic toxicity. As an example of this utility, our previous research developed CD117 (c-kit)-targeted nanoparticles to preferentially target blast-crisis chronic myeloid leukemia cells in an in vivo murine model. Overall, my research program embraces nanotechnology platforms as a means to enhance therapeutics identified through mechanistic laboratory science and screening processes. The ability to validate experimental therapeutics in robust animal models is a hallmark of my lab’s endeavors.​
  • Publications

    Academic Article

    Year Title
    2018 Epigenetics and Sphingolipid Metabolism in Health and Disease.Int J Biopharm Sci.  1:105-105. 2018
    2018 Therapeutic effect of Northern Labrador tea extracts for acute myeloid leukemia.Phytotherapy Research.  32:1636-1641. 2018
    2018 Combinatorial Efficacy of Quercitin and Nanoliposomal Ceramide for Acute Myeloid Leukemia.Int J Biopharm Sci.  1:106-106. 2018
    2018 Therapeutic Effect of Blueberry Extracts for Acute Myeloid Leukemia.Int J Biopharm Sci.  1. 2018
    2016 Acid ceramidase is upregulated in AML and represents a novel therapeutic target.Oncotarget.  7:83208-83222. 2016
    2016 Ceramide-tamoxifen regimen targets bioenergetic elements in acute myelogenous leukemia.Journal of Lipid Research.  57:1231-1242. 2016
    2015 Modification of sphingolipid metabolism by tamoxifen and N-desmethyltamoxifen in acute myelogenous leukemia--Impact on enzyme activity and response to cytotoxics.Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids.  1851:919-928. 2015
    2014 Extracts of Devil's club (Oplopanax horridus) exert therapeutic efficacy in experimental models of acute myeloid leukemia.Phytotherapy Research.  28:1308-1314. 2014
    2014 Maritoclax induces apoptosis in acute myeloid leukemia cells with elevated Mcl-1 expression.Cancer Biology and Therapy.  15:1077-1086. 2014
    2014 Cholecystokinin mediates progression and metastasis of pancreatic cancer associated with dietary fat.Digestive Diseases and Sciences.  59:1180-1191. 2014
    2013 Ceramide 1-phosphate mediates endothelial cell invasion via the annexin a2-p11 heterotetrameric protein complex.Journal of Biological Chemistry.  288:19726-19738. 2013
    2013 PhotoImmunoNanoTherapy reveals an anticancer role for sphingosine kinase 2 and dihydrosphingosine-1-phosphate.ACS Nano.  7:2132-2144. 2013
    2013 Gaucher's disease and cancer: a sphingolipid perspective.Critical Reviews in Oncogenesis.  18:221-234. 2013
    2012 Ceramide kinase regulates TNFα-stimulated NADPH oxidase activity and eicosanoid biosynthesis in neuroblastoma cells.Cellular Signalling.  24:1126-1133. 2012
    2012 Calcium phosphosilicate nanoparticles for imaging and photodynamic therapy of cancer.Discovery medicine.  13:275-285. 2012
    2012 Neutral sphingomyelinase activation precedes NADPH oxidase-dependent damage in neurons exposed to the proinflammatory cytokine tumor necrosis factor-α.Journal of Neuroscience Research.  90:229-242. 2012
    2011 Exogenous ceramide-1-phosphate reduces lipopolysaccharide (LPS)-mediated cytokine expression.Journal of Biological Chemistry.  286:44357-44366. 2011
    2011 Ceramide-based therapeutics for the treatment of cancer.Anti-Cancer Agents in Medicinal Chemistry Current Medicinal Chemistry - Anti-Cancer Agents.  11:911-919. 2011
    2011 Combinatorial therapies improve the therapeutic efficacy of nanoliposomal ceramide for pancreatic cancer.Cancer Biology and Therapy.  12:574-585. 2011
    2011 Targeted indocyanine-green-loaded calcium phosphosilicate nanoparticles for in vivo photodynamic therapy of leukemia.ACS Nano.  5:5325-5337. 2011
    2011 Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma.Gut.  60:695-701. 2011
    2011 Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin.Nature Medicine.  17:55-63. 2011
    2010 Inhibition of NADPH oxidase by glucosylceramide confers chemoresistance.Cancer Biology and Therapy.  10:1126-1136. 2010
    2010 Metabolism of short-chain ceramide by human cancer cells--implications for therapeutic approaches.Biochemical Pharmacology.  80:308-315. 2010
    2010 Bioconjugation of calcium phosphosilicate composite nanoparticles for selective targeting of human breast and pancreatic cancers in vivo.ACS Nano.  4:1279-1287. 2010
    2009 Proinflammatory cytokines provoke oxidative damage to actin in neuronal cells mediated by Rac1 and NADPH oxidase.Molecular and Cellular Neurosciences.  41:274-285. 2009
    2008 Near-infrared emitting fluorophore-doped calcium phosphate nanoparticles for in vivo imaging of human breast cancer.ACS Nano.  2:2075-2084. 2008
    2007 Wild alaskan blueberry extracts inhibit a magnesium-dependent neutral sphingomyelinase activity in neurons exposed to TNF alphaCurrent Topics in Nutraceutical Research.  5:183-188. 2007

    Patents And Disclosures

    Year Title
    Bioconjugation of calcium phosphosilicate nanoparticles for selective targeting of cells in vivo
    Method for Ceramide-Elevating Therapeutic Strategies

    Teaching Activities

  • Doctoral Thesis Taught course 2019
  • Eukaryotic Cell & Devlpmt Biol Taught course 2019
  • Eukaryotic Cell & Devlpmt Biol Taught course 2019
  • Eukaryotic Cell & Devlpmt Biol Taught course 2019
  • Undergrad Teaching Experience Taught course 2019
  • Biochemistry of Cancer Taught course 2018
  • Biochemistry of Cancer Taught course 2018
  • Doctoral Thesis Taught course 2018
  • Doctoral Research Taught course 2018
  • Eukaryotic Cell & Devlpmt Biol Taught course 2018
  • Eukaryotic Cell & Devlpmt Biol Taught course 2018
  • Eukaryotic Cell & Devlpmt Biol Taught course 2018
  • Biochemistry of Cancer Taught course 2017
  • Biochemistry of Cancer Taught course 2017
  • Contemp Top Molec/Cell/Biomed Taught course 2017
  • Doctoral Research Taught course 2017
  • Eukaryotic Cell & Devlpmt Biol Taught course 2017
  • Eukaryotic Cell & Devlpmt Biol Taught course 2017
  • Biochemistry of Cancer Taught course 2016
  • Biochemistry of Cancer Taught course 2016
  • Biochemistry of Cancer Taught course 2016
  • Biochemistry of Cancer Taught course 2016
  • Rsrch Exp/MCBS Taught course 2015
  • Education And Training

  • B.S. Biochemistry and Molecular Biology, Colorado State University
  • M.S. Cell and Molecular Biology, Colorado State University
  • Ph.D. Biochemistry and Molecular Biology, University of Alaska
  • Full Name

  • Brian Barth