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Stephen Howell

Title(s)Recall Hcomp, Medicine
SchoolHealth Sciences
Phone858-822-1112
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    Collapse Overview 
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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

    Collapse Research 
    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
    MOLECULAR PHARMACOLOGY OF PLATINUM DRUG RESISTANCE
    NIH/NCI R01CA069004Aug 1, 1996 - Jul 31, 1999
    Role: Principal Investigator
    MECHANISMS OF PLATINUM DRUG RESIST. IN OVARIAN CARCINOMA
    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
    COMBINATION INTRACAVITARY CHEMOTHERAPY
    NIH/NCI R01CA035309Aug 1, 1983 - May 31, 1989
    Role: Principal Investigator
    Specialized Cancer Center Support Grant
    NIH/NCI P30CA023100Apr 1, 1978 - Apr 30, 2024
    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. Kim B, Sun S, Varner JA, Howell SB, Ruoslahti E, Sailor MJ. Securing the Payload, Finding the Cell, and Avoiding the Endosome: Peptide-Targeted, Fusogenic Porous Silicon Nanoparticles for Delivery of siRNA. Adv Mater. 2019 Jul 03; e1902952. PMID: 31267590.
      View in: PubMed
    2. Bertucci A, Kim KH, Kang J, Zuidema JM, Lee SH, Kwon EJ, Kim D, Howell SB, Ricci F, Ruoslahti E, Jang HJ, Sailor MJ. Tumor-Targeting, MicroRNA-Silencing Porous Silicon Nanoparticles for Ovarian Cancer Therapy. ACS Appl Mater Interfaces. 2019 Jul 10; 11(27):23926-23937. PMID: 31251556.
      View in: PubMed
    3. Proetto MT, Callmann CE, Cliff J, Szymanski CJ, Hu D, Howell SB, Evans JE, Orr G, Gianneschi NC. Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry and Fluorescence Microscopy. ACS Cent Sci. 2018 Nov 28; 4(11):1477-1484. PMID: 30555899.
      View in: PubMed
    4. Local A, Zhang H, Benbatoul KD, Folger P, Sheng X, Tsai CY, Howell SB, Rice WG. APTO-253 Stabilizes G-quadruplex DNA, Inhibits MYC Expression, and Induces DNA Damage in Acute Myeloid Leukemia Cells. Mol Cancer Ther. 2018 06; 17(6):1177-1186. PMID: 29626127.
      View in: PubMed
    5. Tsai CY, Sun S, Zhang H, Local A, Su Y, Gross LA, Rice WG, Howell SB. APTO-253 Is a New Addition to the Repertoire of Drugs that Can Exploit DNA BRCA1/2 Deficiency. Mol Cancer Ther. 2018 06; 17(6):1167-1176. PMID: 29626126.
      View in: PubMed
    6. Schindler AJ, Watanabe A, Howell SB. LGR5 and LGR6 in stem cell biology and ovarian cancer. Oncotarget. 2018 Jan 02; 9(1):1346-1355. PMID: 29416699.
      View in: PubMed
    7. Jandial DA, Brady WE, Howell SB, Lankes HA, Schilder RJ, Beumer JH, Christner SM, Strychor S, Powell MA, Hagemann AR, Moore KN, Walker JL, DiSilvestro PA, Duska LR, Fracasso PM, Dizon DS. A phase I pharmacokinetic study of intraperitoneal bortezomib and carboplatin in patients with persistent or recurrent ovarian cancer: An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2017 05; 145(2):236-242. PMID: 28341300.
      View in: PubMed
    8. Bompiani KM, Tsai CY, Achatz FP, Liebig JK, Howell SB. Copper transporters and chaperones CTR1, CTR2, ATOX1, and CCS as determinants of cisplatin sensitivity. Metallomics. 2016 09 01; 8(9):951-62. PMID: 27157188.
      View in: PubMed
    9. Proetto MT, Anderton CR, Hu D, Szymanski CJ, Zhu Z, Patterson JP, Kammeyer JK, Nilewski LG, Rush AM, Bell NC, Evans JE, Orr G, Howell SB, Gianneschi NC. Cellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic Nanoscopy. ACS Nano. 2016 04 26; 10(4):4046-54. PMID: 27022832.
      View in: PubMed
    10. Muggia FM, Bonetti A, Hoeschele JD, Rozencweig M, Howell SB. 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
    11. Yamamoto T, Tsigelny IF, Götz AW, Howell SB. Cisplatin inhibits MEK1/2. Oncotarget. 2015 Sep 15; 6(27):23510-22. PMID: 26155939.
      View in: PubMed
    12. Tsai CY, Liebig JK, Tsigelny IF, Howell SB. 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.
      View in: PubMed
    13. Sugahara KN, Scodeller P, Braun GB, de Mendoza TH, Yamazaki CM, Kluger MD, Kitayama J, Alvarez E, Howell SB, 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.
      View in: PubMed
    14. Shang X, Lin X, Howell SB. Claudin-4 controls the receptor tyrosine kinase EphA2 pro-oncogenic switch through ß-catenin. Cell Commun Signal. 2014 Oct 25; 12:59. PMID: 25344320.
      View in: PubMed
    15. Wang Y, Ma J, Shen H, Wang C, Sun Y, Howell SB, 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
    16. Tsai CY, Larson CA, Safaei R, Howell SB. 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.
      View in: PubMed
    17. 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.
      View in: PubMed
    18. Huang CP, Fofana M, Chan J, Chang CJ, Howell SB. Copper transporter 2 regulates intracellular copper and sensitivity to cisplatin. Metallomics. 2014 Mar; 6(3):654-61. PMID: 24522273.
      View in: PubMed
    19. Abada PB, Howell SB. Cisplatin induces resistance by triggering differentiation of testicular embryonal carcinoma cells. PLoS One. 2014; 9(1):e87444. PMID: 24475288.
      View in: PubMed
    20. Proetto MT, Rush AM, Chien MP, Abellan Baeza P, Patterson JP, Thompson MP, Olson NH, Moore CE, Rheingold AL, Andolina C, Millstone J, Howell SB, 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.
      View in: PubMed
    21. Quail JF, Tsai CY, Howell SB. 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):151-159. PMID: 24447817.
      View in: PubMed
    22. Safaei R, Adams PL, Mathews RA, Manorek G, Howell SB. 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.
      View in: PubMed
    23. Lin X, Shang X, Manorek G, Howell SB. Regulation of the Epithelial-Mesenchymal Transition by Claudin-3 and Claudin-4. PLoS One. 2013; 8(6):e67496. PMID: 23805314.
      View in: PubMed
    24. Gu L, Hall DJ, Qin Z, Anglin E, Joo J, Mooney DJ, Howell SB, Sailor MJ. In vivo time-gated fluorescence imaging with biodegradable luminescent porous silicon nanoparticles. Nat Commun. 2013; 4:2326. PMID: 23933660.
      View in: PubMed
    25. Shang X, Lin X, Manorek G, Howell SB. 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
    26. Shang X, Lin X, Alvarez E, Manorek G, Howell SB. Tight junction proteins claudin-3 and claudin-4 control tumor growth and metastases. Neoplasia. 2012 Oct; 14(10):974-85. PMID: 23097631.
      View in: PubMed
    27. Tsai CY, Finley JC, Ali SS, Patel HH, Howell SB. 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.
      View in: PubMed
    28. Tsigelny IF, Sharikov Y, Greenberg JP, Miller MA, Kouznetsova VL, Larson CA, Howell SB. An all-atom model of the structure of human copper transporter 1. Cell Biochem Biophys. 2012 Jul; 63(3):223-34. PMID: 22569840.
      View in: PubMed
    29. Abada PB, Larson CA, Manorek G, Adams P, Howell SB. 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.
      View in: PubMed
    30. Gold MA, Brady WE, Lankes HA, Rose PG, Kelley JL, De Geest K, Crispens MA, Resnick KE, Howell SB. A phase II study of a urokinase-derived peptide (A6) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2012 Jun; 125(3):635-9. PMID: 22446624.
      View in: PubMed
    31. Safaei R, Adams PL, Maktabi MH, Mathews RA, Howell SB. 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.
      View in: PubMed
    32. Peng LX, Yu L, Howell SB, 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
    33. Peng LX, Yu L, Howell SB, Gough DA. Aggregation properties of a polymeric anticancer therapeutic: a coarse-grained modeling study. J Chem Inf Model. 2011 Dec 27; 51(12):3030-5. PMID: 21995420.
      View in: PubMed
    34. Piotrowicz RS, Damaj BB, Hachicha M, Incardona F, Howell SB, 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
    35. Park JS, Kinsella JM, Jandial DD, Howell SB, Sailor MJ. Cisplatin-loaded porous Si microparticles capped by electroless deposition of platinum. Small. 2011 Jul 18; 7(14):2061-9. PMID: 21630444.
      View in: PubMed
    36. Xiao L, Gu L, Howell SB, 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.
      View in: PubMed
    37. Peng LX, Das SK, Yu L, Howell SB, 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.
      View in: PubMed
    38. Kanatani I, Lin X, Yuan X, Manorek G, Shang X, Cheung LH, Rosenblum MG, Howell SB. Targeting granzyme B to tumor cells using a yoked human chorionic gonadotropin. Cancer Chemother Pharmacol. 2011 Oct; 68(4):979-90. PMID: 21327682.
      View in: PubMed
    39. Yuan X, Lin X, Manorek G, Howell SB. 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.
      View in: PubMed