Researcher Profile

Researcher Profile

Charles Smith, PhD

Charles Smith, PhD

Professor, Department of Pharmacology
Scientific Program:Experimental Therapeutics
cds9@psu.edu

Research Interests

Research in Dr. Charles Smith's laboratory relates to cancer pharmacology, with a focus on studying the molecular mechanisms of action of established and experimental anticancer drugs, and on designing and developing new drugs against novel molecular targets.

This effort utilizes a multidisciplinary approach that includes biochemical characterization of selected targets for new drugs, synthesis of novel inhibitors of these targets and pharmacological evaluation of the activities of these compounds in both in vitro and in vivo model systems.

The emphasis is currently on studying the roles of sphingolipid metabolizing enzymes, and developing inhibitors of these enzymes.

The Smith lab has synthesized and extensively characterized small molecule inhibitors of sphingosine kinases (SK1 and SK2), which are key regulators of cancer cell proliferation and inflammation. The lab's most-advanced SK2 inhibitor (ABC294640) is currently in multiple clinical trials in cancer patients.

  • Neoplasms
  • sphingosine kinase
  • Proteins
  • Pharmaceutical Preparations
  • Therapeutics
  • P-Glycoprotein
  • Multiple Drug Resistance
  • Growth
  • Apoptosis
  • Phosphorylation
  • Phosphatidylinositol Phosphates
  • Protein Kinases

Recent Publications

2018

Selvam, SP, Roth, BM, Nganga, R, Kim, J, Cooley, MA, Helke, K, Smith, C & Ogretmen, B 2018, 'Balance between senescence and apoptosis is regulated by telomere damage–induced association between p16 and caspase-3', Journal of Biological Chemistry, vol. 293, no. 25, pp. 9784-9800. https://doi.org/10.1074/jbc.RA118.003506
Schrecengost, RS, Green, CL, Zhuang, Y, Keller, SN, Smith, RA, Maines, LW & Smith, C 2018, 'In vitro and in vivo antitumor and anti-inflammatory capabilities of the novel GSK3 and CDK9 inhibitor ABC1183s', Journal of Pharmacology and Experimental Therapeutics, vol. 365, no. 1, pp. 107-116. https://doi.org/10.1124/jpet.117.245738
Lewis, CS, Voelkel-Johnson, C & Smith, C 2018, Targeting Sphingosine Kinases for the Treatment of Cancer. in CE Chalfant & PB Fisher (eds), Advances in Cancer Research. Advances in Cancer Research, vol. 140, Academic Press Inc., pp. 295-325. https://doi.org/10.1016/bs.acr.2018.04.015
Dai, L, Smith, C, Foroozesh, M, Miele, L & Qin, Z 2018, 'The sphingosine kinase 2 inhibitor ABC294640 displays anti-non-small cell lung cancer activities in vitro and in vivo', International Journal of Cancer, vol. 142, no. 10, pp. 2153-2162. https://doi.org/10.1002/ijc.31234

2017

Britten, CD, Garrett-Mayer, E, Chin, SH, Shirai, K, Ogretmen, B, Bentz, TA, Brisendine, A, Anderton, K, Cusack, SL, Maines, LW, Zhuang, Y, Smith, C & Thomas, MB 2017, 'A phase I study of ABC294640, a first-in-class sphingosine kinase-2 inhibitor, in patients with advanced solid tumors', Clinical Cancer Research, vol. 23, no. 16, pp. 4642-4650. https://doi.org/10.1158/1078-0432.CCR-16-2363
Dai, L, Bai, A, Smith, C, Rodriguez, PC, Yu, F & Qin, Z 2017, 'ABC294640, A novel sphingosine kinase 2 inhibitor, induces oncogenic virus–infected cell autophagic death and represses tumor growth', Molecular cancer therapeutics, vol. 16, no. 12, pp. 2724-2734. https://doi.org/10.1158/1535-7163.MCT-17-0485
Sommer, G, Fedarovich, A, Kota, V, Rodriguez, R, Smith, C & Heise, T 2017, 'Applying a high-Throughput fluorescence polarization assay for the discovery of chemical probes blocking La:RNA interactions in vitro and in cells', PloS one, vol. 12, no. 3, e0173246. https://doi.org/10.1371/journal.pone.0173246
Prinsep, MR, Appleton, TG, Hanson, GR, Lane, I, Smith, C, Puddick, J & Fairlie, DP 2017, 'Tolyporphin Macrocycles from the Cyanobacterium Tolypothrix nodosa Selectively Bind Copper and Silver and Reverse Multidrug Resistance', Inorganic Chemistry, vol. 56, no. 10, pp. 5577-5585. https://doi.org/10.1021/acs.inorgchem.6b03000

2016

Ding, X, Chaiteerakij, R, Moser, CD, Shaleh, H, Boakye, J, Chen, G, Ndzengue, A, Li, Y, Zhou, Y, Huang, S, Sinicrope, FA, Zou, X, Thomas, MB, Smith, C & Roberts, LR 2016, 'Antitumor effect of the novel sphingosine kinase 2 inhibitor ABC294640 is enhanced by inhibition of autophagy and by sorafenib in human cholangiocarcinoma cells', Oncotarget, vol. 7, no. 15, pp. 20080-20092. https://doi.org/10.18632/oncotarget.7914
Lewis, CS, Voelkel-Johnson, C & Smith, C 2016, 'Suppression of c-Myc and RRM2 expression in pancreatic cancer cells by the sphingosine kinase-2 inhibitor ABC294640', Oncotarget, vol. 7, no. 37, pp. 60181-60192. https://doi.org/10.18632/oncotarget.11112

2015

Panneer Selvam, S, De Palma, RM, Oaks, JJ, Oleinik, N, Peterson, YK, Stahelin, RV, Skordalakes, E, Ponnusamy, S, Garrett-Mayer, E, Smith, C & Ogretmen, B 2015, 'Binding of the sphingolipid S1P to hTERT stabilizes telomerase at the nuclear periphery by allosterically mimicking protein phosphorylation', Science Signaling, vol. 8, no. 381, pp. ra58. https://doi.org/10.1126/scisignal.aaa4998
Dai, L, Trillo-Tinoco, J, Bai, A, Chen, Y, Bielawski, J, Valle, LD, Smith, C, Ochoa, AC, Qin, Z & Parsons, C 2015, 'Ceramides promote apoptosis for virus-infected lymphoma cells through induction of ceramide synthases and viral lytic gene expression' Oncotarget, vol. 6, no. 27, pp. 24246-24260. https://doi.org/10.18632/oncotarget.4759
Schrecengost, RS, Keller, SN, Schiewer, MJ, Knudsen, KE & Smith, C 2015, 'Downregulation of critical oncogenes by the selective SK2 Inhibitor ABC294640 hinders prostate cancer progression', Molecular Cancer Research, vol. 13, no. 12, pp. 1591-1601. https://doi.org/10.1158/1541-7786.MCR-14-0626
Venant, H, Rahmaniyan, M, Jones, EE, Lu, P, Lilly, MB, Garrett-Mayer, E, Drake, RR, Kraveka, JM, Smith, C & Voelkel-Johnson, C 2015, 'The sphingosine kinase 2 inhibitor ABC294640 reduces the growth of prostate cancer cells and results in accumulation of dihydroceramides in vitro and in vivo', Molecular cancer therapeutics, vol. 14, no. 12, pp. 2744-2752. https://doi.org/10.1158/1535-7163.MCT-15-0279
Jones, EE, Gao, P, Smith, C, Norris, JS & Drake, RR 2015, 'Tissue biomarkers of drug efficacy: Case studies using a MALDI-MSI workflow' Bioanalysis, vol. 7, no. 20, pp. 2611-2619. https://doi.org/10.4155/bio.15.174

Clinical Trials Search


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Adults (age >= 18 years)