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Elizabeth Hopper-Borge, PhD

Elizabeth Hopper-Borge, PhD
About

Assistant Professor

Research Program

MRP7 is expressed ubiquitously
Abcc10 null mice are hypersensitive to paclitaxel. Cancer Research, 2011.

 

Education, Training & Credentials

Educational Background

  • PhD, Biochemistry and Molecular Biophysics, University of Pennsylvania, 1994 - 1999
  • BA, Biological Chemistry, Oberlin College, 1988 - 1991

Memberships

  • American Association for Cancer Research
  • American Diabetes Assocation

Honors & Awards

  • Minority Scholar Award in Cancer Research, American Association for Cancer Research, 2004
  • NIGMS Minority Supplement, 2002
  • Fontaine Fellowship, University of Pennsylvania, 1994-1999
  • NIGMS Predoctoral Fellowship (F31), 1994-1999
  • COSEN Scholarship, 1991
  • GE Minority Scholar, 1988-1992
Research Profile

Research Program

Research Interests

  • Determine the In Vivo role of Abcc10/ABCC10 in resistance
  • Physiological Role of ABCC10
  • Biochemistry of ABCC10
  • Development of an ABCC10 specific inhibitor

Lab Overview

1. Determine the In Vivo role of Abcc10/ABCC10 in resistance

Joely Jacobs

ATP-Binding Cassette (ABC) family of transporters extrude a variety of substrates from cells including anticancer agents, bile acids, sterols and moieties bound to glutathione or glucuronidate. Our laboratory is particularly interested in ascertaining MRP7's (ABCC10's) physiology as well as its role in cancer resistance. Recently, using HEK 293- ABCC10 cell lines we have demonstrated that MRP7 confers resistance to taxanes and nucleoside analogs that are used in the treatment of various cancers. Our laboratory has created several mouse models and is using these models in conjunction with pharmacokinetic techniques to elucidate Mrp7's contribution to in vivo resistance.

 2. Biochemistry of ABCC10

Joely Jacobs & Ekaterina Malofeeva

We are examining the underlying biochemical requirements for MRP7 (ABCC10) activity. Interestingly ABCC10 has the ability to confer resistance to nucleoside analogs and natural products, this is a unique characteristic of this ABCC family member. Further, ABCC10 has some substrate overlap with another well known, very well characterized ABC transporter, P-glycoprotein. We will use biochemical techniques to further defineABCC10’s activity, as well as to identify sites that ABCC10 requires to actively transport its substrates. We can also use these techniques to characterize and find inhibitors of ABCC10 activity.

 3. Physiological Role of ABCC10

 Joely Jacobs

Our laboratory is actively investigating the role of ABCC10 in cancer and normal tissues by identifying physiological substrates of this protein and determining tissue polarity. Toward this end we have developed several mouse models for use in these investigations. We are  supplementing the in vivo models with the use of other in vitro model systems.

 4. Development of an ABCC10 specific inhibitor

Elizabeth Hopper-Borge, Michael Levin

In recently published work we demonstrated that ABCC10 knockdown results in solid tumor in mice also promotes a less aggressive cancer phenotype. In a collaboration we are developing a specific ABCC10 inhibitor. Recent unpublished work from our laboratory indicates that simultaneous  inhibition of ABCC10 and  another well known taxane pump causes  lethality in mice receiving taxane treatment. Many of the currently available ABCC10 inhibitors are non specific and  inhibit other ABC transporters, hence the need to develop a novel ABCC10 inhibitor.

People

Janet Wangari-Talbot, PhD

Postdoctoral Associate

Room: W463
215-214-3757

Additional Staff

Joely Jacobs, Technical Specialist
Liqi Chen, Student Assistant
Nicholas Elmer, Student Assistant
Su Lee, Student Assistant
Michaelle Tran, Student Assistant
Robert Burg, Student Assistant
Michael Levine, Student Assistant

Publications

Selected Publications

Chen, Z-S, Hopper-Borge, E, Belinsky, MG, Shchaveleva, I, Kotova, E, Kruh, GD. Characterization of the transport properties of human multidrug resistance protein 7 (MRP7, ABCC10). Mol. Pharmacol. 63:351-358, 2003. PubMed

Guo, Y, Kotova, E, Chen, Z-S, Lee, K, Hopper-Borge, E, Belinsky, MG, Kruh, GD. MRP8 (ABCC11) is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines, 23-dideoxycytidine and 9-(2-phosphonylmethoxyethyl)-adenine. J. Biol. Chem. 278: 29509-29514, 2003. PubMed

Hopper-Borge, E, Chen, Z-S, Shchaveleva, I, Belinsky, MG, Kruh, GD. Analysis of the drug resistance profile of MRP7 (ABCC10): resistance to docetaxel. Cancer Res. 64:4927-4930, 2004. PubMed

Risinger, AL, Jackson, EM, Polin, LA, Helms, GL, LeBoeuf, DA, Joe, PA, Hopper-Borge, E, Luduena, RF, Kruh, GD., Mooberry, SL. The taccolonides: microtubule stabilizers that circumvent clinically relevant taxane resistant mechanisms. Cancer Res. 68:8881-8888, 2008. PMC2727482 PubMed

Hopper-Borge, E, Xu, X, Shen, T, Shi, Z, Chen, ZS, Kruh, GD. Human multidrug resistance protein 7 (ABCC10) is a resistance factor for nucleoside analogues and epothilone B. Cancer Res. 69:178-184, 2009. PMC2745904 PubMed

Zhou, Y, Hopper-Borge, E, Shi, Z, Shen, T, Furukawa, T, Akiyama, S, Peng, XX, Huang, X.C., Ashby, C., Kruh, G.D., Chen, Z.S. Cepharanthine is a potent reversal agent for MRP7-mediated multidrug resistance. Biochem. Pharmacol. 77:993-1001, 2009. NIHMS84766 PubMed

Kuang, YH, Shen T, Chen X, Sodani K, Hopper-Borge E, Tiwari, AK, Lee JW, Fu LW, Chen, ZS. Lapatinib and erlotinib are potent reversal agents for MPR7 (ABCC10) mediated multidrug resistance. Biochem. Pharmacol. Jan 15;79(2):154-61, 2009. PubMed

Shen, T, Kuang, Y., Ashby, CR, Lei, Y, Chen, A, Zhou, Y, Chen, X, Tiwari, AK, Hopper-Borge, E, Ouyang, J, Chen Z-S. Imatinib and nilotinib reverse multidrug resistance in cancer cells by inhibiting the efflux activity of the MRP7 (ABCC10). PLoS One 4(10):e7520, 2009. PMCID: PMC2759525 PubMed

Hopper-Borge, EA*, Churchill, T, Paulose C, Nicolas, E, Jacobs, JD, Ngo, O, Kuang, Y, Grinberg, Al, Westphal, H, Chen, ZS, Klein-Szanto, AJ, Belinsky, MG, Kruh, GD. Contribution of Abcc10 (Mrp7) to in vivo paclitaxel resistance as assessed in Abcc10-/- mice, Cancer Res. 2011;71(10):3649-3657. 2011 PMID:21576088This paper was selected by the Faculty of 1000 in 2011; http://f1000.com/7256956 * corresponding author PubMed

Pushpakom, SP, Liptrott, N, Rodriguez-Novoa, S., Labarga, P, Soriano, V., Albalater, M, Hopper-Borge, E, Back, D., Khoo, S, Pirmohamed, M, Owen, A. Genetic variants of ABCC10, a novel tenofovir transporter are associated with kidney tubular dysfunction. Journal of Infectious Diseases, J Infect Dis. 2011 Jul; 204(1):145-53. PubMed

Liptrott NJ, Pushpakom S, Wyen C, Fätkenheuer G, Hoffmann C, Mauss S, Knechten H, Brockmeyer NH, Hopper-Borge E, Siccardi M, Back DJ, Khoo SH, Pirmohamed M, Owen Association of ABCC10 polymorphisms with nevirapine plasma concentrations in the German Competence Network for HIV/AIDs. Pharmacogenet Genomics. 2011 Nov 11. PubMed

Malofeeva, EV, Domanitskaya, N, Gudima, M, and Hopper-Borge, E. Modulation of the ATPase and transport activities of broad specificity multidrug resistance factor ABCC10 (MRP7), Cancer Research, 2012 Dec 15;72(24):6457-67.Epub 2012 Oct. 19th. PMID:23087055 PubMed

Domanitskaya, N, Wangari-Talbot J, Jacobs J, Peiffer E, Mahdaviyeh Y, Paulose C, Malofeeva, E, Foster K, Cai KQ, Zhou Y, Egleston B, Hopper-Borge E. Abcc10 status affect mammary tumour growth, metastasis, and docetaxel treatment response.Br. J Cancer 2014 Aug 12;111(4):696-707 PMID:24937672 PubMed 

Jacobs, J and Hopper-Borge, E, Carotid Artery Infusions for Pharmacokinetic and Pharmacodynamic Analysis of Taxanes in Mice. JOVE. 2014 Oct 27;(92): Issue 92; doi: 10.3791/51917 PMID:25407935 PubMed

Teijaro CN, Munagala S, Zhao S, Sirasani G, Kokkonda P, Malofeeva EV, Hopper-Borge E, Andrade RB. Synthesis and Biological Evaluation of Pentacyclic Strychnos Alkaloids as Selective Modulators of the ABCC10 (MRP7) Efflux Pump. J Med Chem. 2014 Dec 26;57(24):10383-90. doi: 10.1021/jm501189p. Epub 2014 Dec 8.PMID:25419978 PubMed

Additional Publications

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