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    Stephen Howell

    SchoolUniversity of California, San Diego
    Address9500 Gilman Drive #0819
    CA La Jolla 92093
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      Research Interests
      Dr. Stephen Howell’s work focuses on the development of novel drugs and drug delivery systems for the treatment of cancer, and on the molecular and genetic mechanisms underlying the development of drug resistance.  He conducted much of the early pharmacokinetic information and clinical trials work on intraperitoneal chemotherapy for the treatment of ovarian cancer.  His laboratory has contributed importantly to the current understanding of how the platinum-containing drugs enter, traffic through and exit from ovarian cancer cells, and how much cells become resistant to these drugs.

      Education and Training
      BA - University of Chicago - 1966
      MD - Harvard Medical School - 1970
      Intern/Resident - Massachusetts General Hospital - 1970-1972
      Research Associate - Laboratory of Cell Biology, NCI - 1972-1974
      Resident - University of California Hospitals - 1974-1975
      Fellow - Oncology, Dana Farber Cancer Institute - 1975-1977

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      Collapse Research Activities and Funding
      In vivo detection and genome-wide location analysis of DNA-adducts
      NIH/NCI R21CA177519Sep 3, 2013 - Aug 31, 2016
      Role: Principal Investigator
      Control of the cellular pharmacology of the platinum-containing drugs by CTR1
      NIH/NCI R01CA152185Jun 18, 2010 - Apr 30, 2015
      Role: Principal Investigator
      UCSD Cancer Center Training Program in Drug Development
      NIH/NCI T32CA121938Jul 1, 2006 - Jun 30, 2021
      Role: Principal Investigator
      Center of Nanotechnology for Treatment, Understanding, *
      NIH/NCI U54CA119335Sep 30, 2005 - Dec 31, 2011
      Role: Co-Investigator
      The Center for Cancer Drug Development (C2D2)
      NIH/NCI U56CA110111Jul 5, 2004 - Jun 30, 2006
      Role: Principal Investigator
      Cisplatin resistance mediated by copper export pathways
      NIH/NCI R01CA095298May 1, 2002 - Jan 31, 2015
      Role: Principal Investigator
      Cisplatin resistance due to loss of DNA mismatch repair
      NIH/NCI R01CA078648Jul 1, 1998 - Apr 30, 2007
      Role: Principal Investigator
      NIH/NCI R01CA069004Aug 1, 1996 - Jul 31, 1999
      Role: Principal Investigator
      NIH/NCI R55CA055725Sep 30, 1992 - Sep 29, 1994
      Role: Principal Investigator
      IVEM and Image Analysis Resource
      NIH/NCRR P41RR004050Dec 12, 1988 - Mar 31, 2014
      Role: Co-Investigator
      NIH/NCI R01CA035309Aug 1, 1983 - May 31, 1989
      Role: Principal Investigator
      Specialized Cancer Center Support Grant
      NIH/NCI P30CA023100Apr 1, 1978 - Apr 30, 2019
      Role: Co-Investigator

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      Collapse Bibliographic 
      Collapse Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
      List All   |   Timeline
      1. Bompiani KM, Tsai CY, Achatz FP, Liebig JK, Howell S. Copper transporters and chaperones CTR1, CTR2, ATOX1, and CCS as determinants of cisplatin sensitivity. Metallomics. 2016 Sep 01; 8(9):951-62. PMID: 27157188; PMCID: PMC5025354 [Available on 09/01/17].
      2. Muggia FM, Bonetti A, Hoeschele JD, Rozencweig M, Howell S. Platinum Antitumor Complexes: 50 Years Since Barnett Rosenberg's Discovery. J Clin Oncol. 2015 Dec 10; 33(35):4219-26. PMID: 26503202.
        View in: PubMed
      3. Yamamoto T, Tsigelny IF, Götz AW, Howell S. Cisplatin inhibits MEK1/2. Oncotarget. 2015 Sep 15; 6(27):23510-22. PMID: 26155939; PMCID: PMC4695133.
      4. Tsai CY, Liebig JK, Tsigelny IF, Howell S. The copper transporter 1 (CTR1) is required to maintain the stability of copper transporter 2 (CTR2). Metallomics. 2015 Nov; 7(11):1477-87. PMID: 26205368; PMCID: PMC4635045.
      5. Sugahara KN, Scodeller P, Braun GB, de Mendoza TH, Yamazaki CM, Kluger MD, Kitayama J, Alvarez E, Howell S, Teesalu T, Ruoslahti E, Lowy AM. A tumor-penetrating peptide enhances circulation-independent targeting of peritoneal carcinomatosis. J Control Release. 2015 Aug 28; 212:59-69. PMID: 26071630; PMCID: PMC4508207.
      6. Shang X, Lin X, Howell S. Claudin-4 controls the receptor tyrosine kinase EphA2 pro-oncogenic switch through ß-catenin. Cell Commun Signal. 2014; 12(1):59. PMID: 25344320.
        View in: PubMed
      7. Wang Y, Ma J, Shen H, Wang C, Sun Y, Howell S, Lin X. Reactive oxygen species promote ovarian cancer progression via the HIF-1a/LOX/E-cadherin pathway. Oncol Rep. 2014 Nov; 32(5):2150-8. PMID: 25174950.
        View in: PubMed
      8. Tsai CY, Larson CA, Safaei R, Howell S. Molecular modulation of the copper and cisplatin transport function of CTR1 and its interaction with IRS-4. Biochem Pharmacol. 2014 Aug 15; 90(4):379-87. PMID: 24967972; PMCID: PMC4343213.
      9. Lin X, Shang X, Manorek G, Fofana M, Stephen B H. Integrin aV modulates the cellular pharmacology of copper and cisplatin by regulating expression of the influx transporter CTR1. Oncoscience. 2014; 1(3):185-195. PMID: 25594011; PMCID: PMC4278295.
      10. Huang CP, Fofana M, Chan J, Chang CJ, Howell S. Copper transporter 2 regulates intracellular copper and sensitivity to cisplatin. Metallomics. 2014 Mar; 6(3):654-61. PMID: 24522273; PMCID: PMC3982597.
      11. Abada PB, Howell S. Cisplatin induces resistance by triggering differentiation of testicular embryonal carcinoma cells. PLoS One. 2014; 9(1):e87444. PMID: 24475288; PMCID: PMC3903721.
      12. Proetto MT, Rush AM, Chien MP, Abellan Baeza P, Patterson JP, Thompson MP, Olson NH, Moore CE, Rheingold AL, Andolina C, Millstone J, Howell S, Browning ND, Evans JE, Gianneschi NC. Dynamics of soft nanomaterials captured by transmission electron microscopy in liquid water. J Am Chem Soc. 2014 Jan 29; 136(4):1162-5. PMID: 24422495; PMCID: PMC4021868.
      13. Quail JF, Tsai CY, Howell S. Characterization of a monoclonal antibody capable of reliably quantifying expression of human Copper Transporter 1 (hCTR1). J Trace Elem Med Biol. 2014 Apr; 28(2):151-9. PMID: 24447817; PMCID: PMC3989404.
      14. Safaei R, Adams PL, Mathews RA, Manorek G, Howell S. The role of metal binding and phosphorylation domains in the regulation of cisplatin-induced trafficking of ATP7B. Metallomics. 2013 Aug; 5(8):964-72. PMID: 23803742; PMCID: PMC4030745.
      15. Lin X, Shang X, Manorek G, Howell S. Regulation of the Epithelial-Mesenchymal Transition by Claudin-3 and Claudin-4. PLoS One. 2013; 8(6):e67496. PMID: 23805314; PMCID: PMC3689737.
      16. Gu L, Hall DJ, Qin Z, Anglin E, Joo J, Mooney DJ, Howell S, Sailor MJ. In vivo time-gated fluorescence imaging with biodegradable luminescent porous silicon nanoparticles. Nat Commun. 2013; 4:2326. PMID: 23933660; PMCID: PMC4154512.
      17. Shang X, Lin X, Manorek G, Howell S. Claudin-3 and claudin-4 regulate sensitivity to cisplatin by controlling expression of the copper and cisplatin influx transporter CTR1. Mol Pharmacol. 2013 Jan; 83(1):85-94. PMID: 23053666.
        View in: PubMed
      18. Shang X, Lin X, Alvarez E, Manorek G, Howell S. Tight junction proteins claudin-3 and claudin-4 control tumor growth and metastases. Neoplasia. 2012 Oct; 14(10):974-85. PMID: 23097631; PMCID: PMC3479841.
      19. Tsai CY, Finley JC, Ali SS, Patel HH, Howell S. Copper influx transporter 1 is required for FGF, PDGF and EGF-induced MAPK signaling. Biochem Pharmacol. 2012 Oct 15; 84(8):1007-13. PMID: 22842628; PMCID: PMC3464187.
      20. Tsigelny IF, Sharikov Y, Greenberg JP, Miller MA, Kouznetsova VL, Larson CA, Howell S. An all-atom model of the structure of human copper transporter 1. Cell Biochem Biophys. 2012 Jul; 63(3):223-34. PMID: 22569840; PMCID: PMC3590913.
      21. Abada PB, Larson CA, Manorek G, Adams P, Howell S. Sec61ß controls sensitivity to platinum-containing chemotherapeutic agents through modulation of the copper-transporting ATPase ATP7A. Mol Pharmacol. 2012 Sep; 82(3):510-20. PMID: 22710939; PMCID: PMC3422700.
      22. Safaei R, Adams PL, Maktabi MH, Mathews RA, Howell S. The CXXC motifs in the metal binding domains are required for ATP7B to mediate resistance to cisplatin. J Inorg Biochem. 2012 May; 110:8-17. PMID: 22459168; PMCID: PMC3586266.
      23. Peng LX, Yu L, Howell S, Gough DA. Effects of solution concentration on the physicochemical properties of a polymeric anticancer therapeutic. Mol Pharm. 2012 Jan 01; 9(1):37-47. PMID: 21988542.
        View in: PubMed
      24. Piotrowicz RS, Damaj BB, Hachicha M, Incardona F, Howell S, Finlayson M. A6 peptide activates CD44 adhesive activity, induces FAK and MEK phosphorylation, and inhibits the migration and metastasis of CD44-expressing cells. Mol Cancer Ther. 2011 Nov; 10(11):2072-82. PMID: 21885863.
        View in: PubMed
      25. Park JS, Kinsella JM, Jandial DD, Howell S, Sailor MJ. Cisplatin-loaded porous Si microparticles capped by electroless deposition of platinum. Small. 2011 Jul 18; 7(14):2061-9. PMID: 21630444; PMCID: PMC3377373.
      26. Xiao L, Gu L, Howell S, Sailor MJ. Porous silicon nanoparticle photosensitizers for singlet oxygen and their phototoxicity against cancer cells. ACS Nano. 2011 May 24; 5(5):3651-9. PMID: 21452822; PMCID: PMC3104024.
      27. Peng LX, Das SK, Yu L, Howell S, Gough DA. Coarse-grained modeling study of nonpeptide RGD ligand density and PEG molecular weight on the conformation of poly(?-glutamyl-glutamate) paclitaxel conjugates. J Mol Model. 2011 Nov; 17(11):2973-87. PMID: 21360176; PMCID: PMC3203221.
      28. Kanatani I, Lin X, Yuan X, Manorek G, Shang X, Cheung LH, Rosenblum MG, Howell S. Targeting granzyme B to tumor cells using a yoked human chorionic gonadotropin. Cancer Chemother Pharmacol. 2011 Oct; 68(4):979-90. PMID: 21327682; PMCID: PMC3180622.
      29. Yuan X, Lin X, Manorek G, Howell S. Challenges associated with the targeted delivery of gelonin to claudin-expressing cancer cells with the use of activatable cell penetrating peptides to enhance potency. BMC Cancer. 2011 Feb 08; 11:61. PMID: 21303546; PMCID: PMC3042419.
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