Stephen Howell

Title(s)Recall Hcomp, Medicine
SchoolVc-health Sciences-schools
Address9500 Gilman Drive #
La Jolla CA 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 R21CA177519Sep 3, 2013 - Aug 31, 2017
    Role: Principal Investigator
    Control of the cellular pharmacology of the platinum-containing drugs by CTR1
    NIH R01CA152185Jun 18, 2010 - Apr 30, 2015
    Role: Principal Investigator
    UCSD Cancer Center Training Program in Drug Development
    NIH T32CA121938Jul 1, 2006 - Jun 30, 2021
    Role: Principal Investigator
    Center of Nanotechnology for Treatment, Understanding, *
    NIH U54CA119335Sep 30, 2005 - Dec 31, 2011
    Role: Co-Investigator
    The Center for Cancer Drug Development (C2D2)
    NIH U56CA110111Jul 5, 2004 - Jun 30, 2006
    Role: Principal Investigator
    Cisplatin resistance mediated by copper export pathways
    NIH R01CA095298May 1, 2002 - Jan 31, 2015
    Role: Principal Investigator
    Cisplatin resistance due to loss of DNA mismatch repair
    NIH R01CA078648Jul 1, 1998 - Apr 30, 2007
    Role: Principal Investigator
    NIH R01CA069004Aug 1, 1996 - Jul 31, 1999
    Role: Principal Investigator
    NIH R55CA055725Sep 30, 1992 - Sep 29, 1994
    Role: Principal Investigator
    IVEM and Image Analysis Resource
    NIH P41RR004050Dec 12, 1988 - Mar 31, 2014
    Role: Co-Investigator
    NIH R01CA035309Aug 1, 1983 - May 31, 1989
    Role: Principal Investigator
    Specialized Cancer Center Support Grant
    NIH P30CA023100Apr 1, 1978 - Apr 30, 2024
    Role: Co-Investigator

    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. to make corrections and additions.
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    1. Luxeptinib (CG-806) Targets FLT3 and Clusters of Kinases Operative in Acute Myeloid Leukemia. Mol Cancer Ther. 2022 07 05; 21(7):1125-1135. Rice WG, Howell SB, Zhang H, Rastgoo N, Local A, Kurtz SE, Lo P, Bottomly D, Wilmot B, McWeeney SK, Druker BJ, Tyner JW. PMID: 35499387; PMCID: PMC9256809.
      View in: PubMed   Mentions:    Fields:    Translation:HumansAnimalsCells
    2. Single-cell characterization of step-wise acquisition of carboplatin resistance in ovarian cancer. NPJ Syst Biol Appl. 2022 06 17; 8(1):20. Wenzel AT, Champa D, Venkatesh H, Sun S, Tsai CY, Mesirov JP, Bui JD, Howell SB, Harismendy O. PMID: 35715421; PMCID: PMC9206019.
      View in: PubMed   Mentions:    Fields:    Translation:Humans
    3. Luxeptinib disables NLRP3 inflammasome-mediated IL-1β release and pathways required for secretion of inflammatory cytokines IL-6 and TNFα. Biochem Pharmacol. 2022 01; 195:114861. Sonowal H, Zhang H, Rice W, Howell SB. PMID: 34843717.
      View in: PubMed   Mentions:    Fields:    Translation:HumansAnimalsCells
    4. Therapeutic Targeting of Tumor Cells Rich in LGR Stem Cell Receptors. Bioconjug Chem. 2021 02 17; 32(2):376-384. Yu S, Mulero MC, Chen W, Shang X, Tian S, Watanabe J, Watanabe A, Vorberg T, Wong C, Gately D, Howell SB. PMID: 33492953.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansAnimalsCells
    5. WNT Signaling Driven by R-spondin 1 and LGR6 in High-grade Serous Ovarian Cancer. Anticancer Res. 2020 Nov; 40(11):6017-6028. Lee S, Jun J, Kim WJ, Tamayo P, Howell SB. PMID: 33109540; PMCID: PMC9312105.
      View in: PubMed   Mentions: 1     Fields:    Translation:HumansCells
    6. Securing the Payload, Finding the Cell, and Avoiding the Endosome: Peptide-Targeted, Fusogenic Porous Silicon Nanoparticles for Delivery of siRNA. Adv Mater. 2019 Aug; 31(35):e1902952. Kim B, Sun S, Varner JA, Howell SB, Ruoslahti E, Sailor MJ. PMID: 31267590; PMCID: PMC6710136.
      View in: PubMed   Mentions: 13     Fields:    Translation:HumansAnimalsCells
    7. Tumor-Targeting, MicroRNA-Silencing Porous Silicon Nanoparticles for Ovarian Cancer Therapy. ACS Appl Mater Interfaces. 2019 Jul 10; 11(27):23926-23937. Bertucci A, Kim KH, Kang J, Zuidema JM, Lee SH, Kwon EJ, Kim D, Howell SB, Ricci F, Ruoslahti E, Jang HJ, Sailor MJ. PMID: 31251556.
      View in: PubMed   Mentions: 19     Fields:    Translation:HumansAnimalsCells
    8. 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. Proetto MT, Callmann CE, Cliff J, Szymanski CJ, Hu D, Howell SB, Evans JE, Orr G, Gianneschi NC. PMID: 30555899; PMCID: PMC6276039.
      View in: PubMed   Mentions: 6  
    9. 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. Tsai CY, Sun S, Zhang H, Local A, Su Y, Gross LA, Rice WG, Howell SB. PMID: 29626126; PMCID: PMC7087411.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansAnimalsCells
    10. 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. Local A, Zhang H, Benbatoul KD, Folger P, Sheng X, Tsai CY, Howell SB, Rice WG. PMID: 29626127.
      View in: PubMed   Mentions: 20     Fields:    Translation:HumansCells
    11. LGR5 and LGR6 in stem cell biology and ovarian cancer. Oncotarget. 2018 Jan 02; 9(1):1346-1355. Schindler AJ, Watanabe A, Howell SB. PMID: 29416699; PMCID: PMC5787443.
      View in: PubMed   Mentions: 17     Fields:    
    12. 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. 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. PMID: 28341300; PMCID: PMC5706109.
      View in: PubMed   Mentions: 9     Fields:    Translation:HumansCTClinical Trials
    13. Copper transporters and chaperones CTR1, CTR2, ATOX1, and CCS as determinants of cisplatin sensitivity. Metallomics. 2016 09 01; 8(9):951-62. Bompiani KM, Tsai CY, Achatz FP, Liebig JK, Howell SB. PMID: 27157188; PMCID: PMC5025354.
      View in: PubMed   Mentions: 27     Fields:    Translation:HumansAnimalsCells
    14. Cellular Delivery of Nanoparticles Revealed with Combined Optical and Isotopic Nanoscopy. ACS Nano. 2016 04 26; 10(4):4046-54. 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. PMID: 27022832; PMCID: PMC8459375.
      View in: PubMed   Mentions: 8     Fields:    Translation:HumansCells
    15. Platinum Antitumor Complexes: 50 Years Since Barnett Rosenberg's Discovery. J Clin Oncol. 2015 Dec 10; 33(35):4219-26. Muggia FM, Bonetti A, Hoeschele JD, Rozencweig M, Howell SB. PMID: 26503202.
      View in: PubMed   Mentions: 43     Fields:    Translation:Humans
    16. Cisplatin inhibits MEK1/2. Oncotarget. 2015 Sep 15; 6(27):23510-22. Yamamoto T, Tsigelny IF, Götz AW, Howell SB. PMID: 26155939; PMCID: PMC4695133.
      View in: PubMed   Mentions: 3     Fields:    Translation:HumansCells
    17. The copper transporter 1 (CTR1) is required to maintain the stability of copper transporter 2 (CTR2). Metallomics. 2015 Nov; 7(11):1477-87. Tsai CY, Liebig JK, Tsigelny IF, Howell SB. PMID: 26205368; PMCID: PMC4635045.
      View in: PubMed   Mentions: 6     Fields:    Translation:HumansCells
    18. A tumor-penetrating peptide enhances circulation-independent targeting of peritoneal carcinomatosis. J Control Release. 2015 Aug 28; 212:59-69. 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. PMID: 26071630; PMCID: PMC4508207.
      View in: PubMed   Mentions: 29     Fields:    Translation:HumansAnimalsCells
    19. Claudin-4 controls the receptor tyrosine kinase EphA2 pro-oncogenic switch through β-catenin. Cell Commun Signal. 2014 Oct 25; 12:59. Shang X, Lin X, Howell SB. PMID: 25344320; PMCID: PMC4212103.
      View in: PubMed   Mentions: 5     Fields:    Translation:HumansCells
    20. Reactive oxygen species promote ovarian cancer progression via the HIF-1α/LOX/E-cadherin pathway. Oncol Rep. 2014 Nov; 32(5):2150-8. Wang Y, Ma J, Shen H, Wang C, Sun Y, Howell SB, Lin X. PMID: 25174950; PMCID: PMC4440217.
      View in: PubMed   Mentions: 24     Fields:    Translation:HumansAnimalsCells
    21. 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. Tsai CY, Larson CA, Safaei R, Howell SB. PMID: 24967972; PMCID: PMC4343213.
      View in: PubMed   Mentions: 13     Fields:    Translation:AnimalsCells
    22. Integrin αV modulates the cellular pharmacology of copper and cisplatin by regulating expression of the influx transporter CTR1. Oncoscience. 2014; 1(3):185-195. Lin X, Shang X, Manorek G, Fofana M, Stephen B H. PMID: 25594011; PMCID: PMC4278295.
      View in: PubMed   Mentions: 2  
    23. Copper transporter 2 regulates intracellular copper and sensitivity to cisplatin. Metallomics. 2014 Mar; 6(3):654-61. Huang CP, Fofana M, Chan J, Chang CJ, Howell SB. PMID: 24522273; PMCID: PMC3982597.
      View in: PubMed   Mentions: 23     Fields:    Translation:HumansAnimalsCells
    24. Cisplatin induces resistance by triggering differentiation of testicular embryonal carcinoma cells. PLoS One. 2014; 9(1):e87444. Abada PB, Howell SB. PMID: 24475288; PMCID: PMC3903721.
      View in: PubMed   Mentions: 14     Fields:    Translation:HumansCells
    25. Dynamics of soft nanomaterials captured by transmission electron microscopy in liquid water. J Am Chem Soc. 2014 Jan 29; 136(4):1162-5. 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. PMID: 24422495; PMCID: PMC4021868.
      View in: PubMed   Mentions: 13     Fields:    Translation:Cells
    26. 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. Quail JF, Tsai CY, Howell SB. PMID: 24447817; PMCID: PMC3989404.
      View in: PubMed   Mentions: 4     Fields:    Translation:HumansCells
    27. The role of metal binding and phosphorylation domains in the regulation of cisplatin-induced trafficking of ATP7B. Metallomics. 2013 Aug; 5(8):964-72. Safaei R, Adams PL, Mathews RA, Manorek G, Howell SB. PMID: 23803742; PMCID: PMC4030745.
      View in: PubMed   Mentions: 8     Fields:    Translation:HumansCells
    28. Regulation of the Epithelial-Mesenchymal Transition by Claudin-3 and Claudin-4. PLoS One. 2013; 8(6):e67496. Lin X, Shang X, Manorek G, Howell SB. PMID: 23805314; PMCID: PMC3689737.
      View in: PubMed   Mentions: 49     Fields:    Translation:HumansAnimalsCells
    29. In vivo time-gated fluorescence imaging with biodegradable luminescent porous silicon nanoparticles. Nat Commun. 2013; 4:2326. Gu L, Hall DJ, Qin Z, Anglin E, Joo J, Mooney DJ, Howell SB, Sailor MJ. PMID: 23933660; PMCID: PMC4154512.
      View in: PubMed   Mentions: 58     Fields:    Translation:HumansAnimals
    30. 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. Shang X, Lin X, Manorek G, Howell SB. PMID: 23053666.
      View in: PubMed   Mentions: 26     Fields:    Translation:HumansAnimalsCells
    31. Tight junction proteins claudin-3 and claudin-4 control tumor growth and metastases. Neoplasia. 2012 Oct; 14(10):974-85. Shang X, Lin X, Alvarez E, Manorek G, Howell SB. PMID: 23097631; PMCID: PMC3479841.
      View in: PubMed   Mentions: 51     Fields:    Translation:HumansCells
    32. Copper influx transporter 1 is required for FGF, PDGF and EGF-induced MAPK signaling. Biochem Pharmacol. 2012 Oct 15; 84(8):1007-13. Tsai CY, Finley JC, Ali SS, Patel HH, Howell SB. PMID: 22842628; PMCID: PMC3464187.
      View in: PubMed   Mentions: 26     Fields:    Translation:AnimalsCells
    33. An all-atom model of the structure of human copper transporter 1. Cell Biochem Biophys. 2012 Jul; 63(3):223-34. Tsigelny IF, Sharikov Y, Greenberg JP, Miller MA, Kouznetsova VL, Larson CA, Howell SB. PMID: 22569840; PMCID: PMC3590913.
      View in: PubMed   Mentions: 23     Fields:    Translation:HumansCells
    34. Sec61β controls sensitivity to platinum-containing chemotherapeutic agents through modulation of the copper-transporting ATPase ATP7A. Mol Pharmacol. 2012 Sep; 82(3):510-20. Abada PB, Larson CA, Manorek G, Adams P, Howell SB. PMID: 22710939; PMCID: PMC3422700.
      View in: PubMed   Mentions: 9     Fields:    Translation:HumansCells
    35. 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. Gold MA, Brady WE, Lankes HA, Rose PG, Kelley JL, De Geest K, Crispens MA, Resnick KE, Howell SB. PMID: 22446624; PMCID: PMC4370623.
      View in: PubMed   Mentions: 18     Fields:    Translation:HumansCTClinical Trials
    36. 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. Safaei R, Adams PL, Maktabi MH, Mathews RA, Howell SB. PMID: 22459168; PMCID: PMC3586266.
      View in: PubMed   Mentions: 20     Fields:    Translation:HumansCells
    37. Effects of solution concentration on the physicochemical properties of a polymeric anticancer therapeutic. Mol Pharm. 2012 Jan 01; 9(1):37-47. Peng LX, Yu L, Howell SB, Gough DA. PMID: 21988542.
      View in: PubMed   Mentions:    Fields:    Translation:Cells
    38. Aggregation properties of a polymeric anticancer therapeutic: a coarse-grained modeling study. J Chem Inf Model. 2011 Dec 27; 51(12):3030-5. Peng LX, Yu L, Howell SB, Gough DA. PMID: 21995420.
      View in: PubMed   Mentions: 2     Fields:    Translation:Cells
    39. 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. Piotrowicz RS, Damaj BB, Hachicha M, Incardona F, Howell SB, Finlayson M. PMID: 21885863.
      View in: PubMed   Mentions: 24     Fields:    Translation:HumansAnimalsCells
    40. Cisplatin-loaded porous Si microparticles capped by electroless deposition of platinum. Small. 2011 Jul 18; 7(14):2061-9. Park JS, Kinsella JM, Jandial DD, Howell SB, Sailor MJ. PMID: 21630444; PMCID: PMC3377373.
      View in: PubMed   Mentions: 9     Fields:    Translation:HumansCells
    41. Porous silicon nanoparticle photosensitizers for singlet oxygen and their phototoxicity against cancer cells. ACS Nano. 2011 May 24; 5(5):3651-9. Xiao L, Gu L, Howell SB, Sailor MJ. PMID: 21452822; PMCID: PMC3104024.
      View in: PubMed   Mentions: 57     Fields:    Translation:HumansAnimalsCells
    42. Coarse-grained modeling study of nonpeptide RGD ligand density and PEG molecular weight on the conformation of poly(γ-glutamyl-glutamate) paclitaxel conjugates. J Mol Model. 2011 Nov; 17(11):2973-87. Peng LX, Das SK, Yu L, Howell SB, Gough DA. PMID: 21360176; PMCID: PMC3203221.
      View in: PubMed   Mentions: 1     Fields:    Translation:Cells
    43. Targeting granzyme B to tumor cells using a yoked human chorionic gonadotropin. Cancer Chemother Pharmacol. 2011 Oct; 68(4):979-90. Kanatani I, Lin X, Yuan X, Manorek G, Shang X, Cheung LH, Rosenblum MG, Howell SB. PMID: 21327682; PMCID: PMC3180622.
      View in: PubMed   Mentions: 6     Fields:    Translation:HumansAnimalsCells
    44. 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. Yuan X, Lin X, Manorek G, Howell SB. PMID: 21303546; PMCID: PMC3042419.
      View in: PubMed   Mentions: 11     Fields:    Translation:HumansCells
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