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.?
Ph.D., Biochemistry and Molecular Biology, University of Alaska
M.S., Cell and Molecular Biology, Colorado State University
B.S., Biochemistry and Molecular Biology, Colorado State University
BCHM 863: Biochemistry of Cancer
BMCB 605: Eukaryotic Cell & Devlpmt Biol
BMCB 763: Biochemistry of Cancer
BMCB 790: Undergrad Teaching Experience
INCO 590: Rsrch Exp/MCBS
MCBS 905: Contemp Top Molec/Cell/Biomed
MCBS 999: Doctoral Thesis
MESB 999: Doctoral Research
McGill, C. M., Tomco, P. L., Ondrasik, R. M., Belknap, K. C., Dwyer, G. K., Quinlan, D. J., . . . Barth, B. M. (2018). Therapeutic effect of Northern Labrador tea extracts for acute myeloid leukemia. Phytotherapy Research, 32(8), 1636-1641. doi:10.1002/ptr.6091
McGill, C. M., Brown, T. J., Cheng, Y. -Y., Fisher, L. N., Shanmugavelandy, S. S., Gustafson, S. J., . . . Barth, B. M. (2018). Therapeutic Effect of Blueberry Extracts for Acute Myeloid Leukemia.. International journal of biopharmaceutical sciences, 1(1).
Tan, S. -F., Liu, X., Fox, T. E., Barth, B. M., Sharma, A., Turner, S. D., . . . Loughran, T. P. (2016). Acid ceramidase is upregulated in AML and represents a novel therapeutic target. Oncotarget, 7(50). doi:10.18632/oncotarget.13079
Morad, S. A. F., Ryan, T. E., Neufer, P. D., Zeczycki, T. N., Davis, T. S., MacDougall, M. R., . . . Cabot, M. C. (2016). Ceramide-tamoxifen regimen targets bioenergetic elements in acute myelogenous leukemia. Journal of Lipid Research, 57(7), 1231-1242. doi:10.1194/jlr.m067389
Morad, S. A. F., Tan, S. -F., Feith, D. J., Kester, M., Claxton, D. F., Loughran, T. P., . . . Cabot, M. C. (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 (BBA) - Molecular and Cell Biology of Lipids, 1851(7), 919-928. doi:10.1016/j.bbalip.2015.03.001
Barth, B. M., I. Altinoğlu, E., Shanmugavelandy, S. S., Kaiser, J. M., Crespo-Gonzalez, D., DiVittore, N. A., . . . Kester, M. (2011). Targeted Indocyanine-Green-Loaded Calcium Phosphosilicate Nanoparticles for In Vivo Photodynamic Therapy of Leukemia. ACS Nano, 5(7), 5325-5337. doi:10.1021/nn2005766
Tagaram, H. R. S., DiVittore, N. A., Barth, B. M., Kaiser, J. M., Avella, D., Kimchi, E. T., . . . Staveley-O'Carroll, K. F. (2011). Nanoliposomal ceramide prevents in vivo growth of hepatocellular carcinoma. Gut, 60(5), 695-701. doi:10.1136/gut.2010.216671
Holland, W. L., Miller, R. A., Wang, Z. V., Sun, K., Barth, B. M., Bui, H. H., . . . Scherer, P. E. (2011). Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nature Medicine, 17(1), 55-63. doi:10.1038/nm.2277
Barth, B. M., Sharma, R., Altınoǧlu, E. İ., Morgan, T. T., Shanmugavelandy, S. S., Kaiser, J. M., . . . Adair, J. H. (2010). Bioconjugation of Calcium Phosphosilicate Composite Nanoparticles for Selective Targeting of Human Breast and Pancreatic Cancers In Vivo. ACS Nano, 4(3), 1279-1287. doi:10.1021/nn901297q
Altınoǧlu, E. I., Russin, T. J., Kaiser, J. M., Barth, B. M., Eklund, P. C., Kester, M., & Adair, J. H. (2008). Near-Infrared Emitting Fluorophore-Doped Calcium Phosphate Nanoparticles for In Vivo Imaging of Human Breast Cancer. ACS Nano, 2(10), 2075-2084. doi:10.1021/nn800448r