Honors & Awards

  • Undergraduate Research and Teaching Scholar, UCLA Undergraduate Research Center (2007)
  • Tau Beta Pi, UCLA Engineering (2007)
  • Dean's Prize for Outstanding Undergraduate Researcher, UCLA Undergraduate Research Center (2007)
  • Distinguished Senior Award, UCLA Alumni Association (2007)
  • Senior Capstone Design Winner, UCLA Bioengineering (2008)
  • Engineering Honor Dean List, UCLA Engineering (2004 - 2008)
  • Phi Beta Kappa, UCLA (2008)
  • Outstanding Bachelor of Science, Departmental Citation (top graduate), UCLA Bioengineering (2008)
  • Gates Millennium Scholar, The Bill & Melinda Gates Foundation (2004 - 2008)
  • Medical Scholar Fellowship, Stanford University Medical Scholars Program (2008 - 2011)
  • Soros Fellowship, The Paul and Daisy Soros Foundation (2009 - 2011)
  • HHMI Research Fellowship, Howard Hughes Medical Institute (2010 - 2011)
  • International Achievement Summit Delegate, Academy of Achievement (2011)
  • Phi Beta Kappa Graduate Fellowship, Phi Beta Kappa (2013)
  • NRSA F30 for MD/PhD student, NIH/NIDDK (2013-2016)
  • Best Poster Award, Stanford Translational Research and Applied Medicine (TRAM) (2013)

Education & Certifications

  • Bachelor of Science, University of California Los Angeles, Bioengineering (2008)


  • 2015 Autumn - NENS 301A Neurology Core Clerkship
  • 2015 Autumn - PSYC 300A Psychiatry Core Clerkship
  • 2015 Spring - FAMMED 301A Family Medicine Core Clerkship
  • 2015 Spring - PEDS 300A Pediatrics Core Clerkship
  • 2015 Summer - MED 314A Advanced Medicine Clerkship
  • 2015 Summer - MED 313A Ambulatory Medicine Core Clerkship
  • 2015 Summer - MED 398A Clinical Elective in Medicine
  • 2015 Winter - OBGYN 300A Obstetrics and Gynecology Core Clerkship
  • 2015 Winter - PEDS 300A Pediatrics Core Clerkship
  • 2014 Autumn - MED 300A Internal Medicine Core Clerkship
  • 2014 Autumn - SURG 300A Surgery Core Clerkship
  • 2014 Summer - FAMMED 310A Primary Care Continuity Experience
  • 2014 Summer - SURG 300A Surgery Core Clerkship

Research & Scholarship

Current Research and Scholarly Interests

My research interest is translational molecular virology, focusing on hepatitis viruses. Using both biophysical and genetic tools, I aim to identify viral and host targets that are essential in the viral life cycle and subsequently develop high-throughput assays to identify novel compounds that can inhibit these targets. I also have a particular interest in understanding the linkage between various chronic viral infections and cancer through studying how such infections disturb the innate and adaptive immune systems and facilitate the development of cancer.


All Publications

  • Task-Shifting: An Approach to Decentralized Hepatitis C Treatment in Medically Underserved Areas DIGESTIVE DISEASES AND SCIENCES Jayasekera, C. R., Perumpail, R. B., Chao, D. T., Pham, E. A., Aggarwal, A., Wong, R. J., Ahmed, A. 2015; 60 (12): 3552-3557
  • Sofosbuvir and simeprevir combination therapy in the setting of liver transplantation and hemodialysis TRANSPLANT INFECTIOUS DISEASE Perumpail, R. B., Wong, R. J., Ha, L. D., Pham, E. A., Wang, U., Luong, H., Kumari, R., Daugherty, T. J., Higgins, J. P., Younossi, Z. M., Kim, W. R., Glenn, J. S., Ahmed, A. 2015; 17 (2): 275-278


    We report safety, tolerability, and 12-week sustained virologic response with half-standard dose sofosbuvir and standard-dose simeprevir combination therapy in a hepatitis C virus genotype 1a-infected liver transplant recipient on hemodialysis - uncharted territory for sofosbuvir-based therapy. The patient was a non-responder to prior treatment with pegylated interferon plus ribavirin. Sofosbuvir efficacy was maintained despite pill-splitting and administration of half-standard dose, 200 mg per day. No drug-drug interactions were noted with tacrolimus-based immunosuppression. Laboratory tests remained stable or improved during therapy. Our observation, if reproduced in a larger study, may lead to significant improvement in clinical outcomes and cost savings in this patient population.

    View details for DOI 10.1111/tid.12348

    View details for Web of Science ID 000352219400013

  • Phosphatidylinositol 4,5-Bisphosphate Is an HCV NS5A Ligand and Mediates Replication of the Viral Genome GASTROENTEROLOGY Cho, N., Lee, C., Pang, P. S., Pham, E. A., Fram, B., Nguyen, K., Xiong, A., Sklan, E. H., Elazar, M., Koytak, E. S., Kersten, C., Kanazawa, K. K., Frank, C. W., Glenn, J. S. 2015; 148 (3): 616-625


    Phosphoinositides (PIs) bind and regulate localization of proteins via a variety of structural motifs. PI 4,5-bisphosphate (PI[4,5]P2) interacts with and modulates the function of several proteins involved in intracellular vesicular membrane trafficking. We investigated interactions between PI(4,5)P2 and hepatitis C virus (HCV) nonstructural protein 5A (NS5A) and effects on the viral life cycle.We used a combination of quartz crystal microbalance, circular dichroism, molecular genetics, and immunofluorescence to study specific binding of PI(4,5)P2 by the HCV NS5A protein. We evaluated the effects of PI(4,5)P2 on the function of NS5A by expressing wild-type or mutant forms of Bart79I or FL-J6/JFH-5'C19Rluc2AUbi21 RNA in Huh7 cells. We also studied the effects of strategies designed to inhibit PI(4,5)P2 on HCV replication in these cells.The N-terminal amphipathic helix of NS5A bound specifically to PI(4,5)P2, inducing a conformational change that stabilized the interaction between NS5A and TBC1D20, which is required for HCV replication. A pair of positively charged residues within the amphipathic helix (the basic amino acid PI(4,5)P2 pincer domain) was required for PI(4,5)P2 binding and replication of the HCV-RNA genome. A similar motif was found to be conserved across all HCV isolates, as well as amphipathic helices of many pathogens and apolipoproteins.PI(4,5)P2 binds to HCV NS5A to promote replication of the viral RNA genome in hepatocytes. Strategies to disrupt this interaction might be developed to inhibit replication of HCV and other viruses.

    View details for DOI 10.1053/j.gastro.2014.11.043

    View details for Web of Science ID 000349968200032

  • Using Chimeric Mice with Humanized Livers to Predict Human Drug Metabolism and a Drug-Drug Interaction JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Nishimura, T., Hu, Y., Wu, M., Pham, E., Suemizu, H., Elazar, M., Liu, M., Idilman, R., Yurdaydin, C., Angus, P., Stedman, C., Murphy, B., Glenn, J., Nakamura, M., Nomura, T., Chen, Y., Zheng, M., Fitch, W. L., Peltz, G. 2013; 344 (2): 388-396


    Interspecies differences in drug metabolism have made it difficult to use preclinical animal testing data to predict the drug metabolites or potential drug-drug interactions (DDIs) that will occur in humans. Although chimeric mice with humanized livers can produce known human metabolites for test substrates, we do not know whether chimeric mice can be used to prospectively predict human drug metabolism or a possible DDI. Therefore, we investigated whether they could provide a more predictive assessment for clemizole, a drug in clinical development for the treatment of hepatitis C virus (HCV) infection. Our results demonstrate, for the first time, that analyses performed in chimeric mice can correctly identify the predominant human drug metabolite before human testing. The differences in the rodent and human pathways for clemizole metabolism were of importance, because the predominant human metabolite was found to have synergistic anti-HCV activity. Moreover, studies in chimeric mice also correctly predicted that a DDI would occur in humans when clemizole was coadministered with a CYP3A4 inhibitor. These results demonstrate that using chimeric mice can improve the quality of preclinical drug assessment.

    View details for DOI 10.1124/jpet.112.198697

    View details for Web of Science ID 000313745900008

  • Structural Map of a MicroRNA-122: Hepatitis C Virus Complex JOURNAL OF VIROLOGY Pang, P. S., Pham, E. A., Elazar, M., Patel, S. G., Eckart, M. R., Glenn, J. S. 2012; 86 (2): 1250-1254


    MicroRNA-122 (miR-122) enhances hepatitis C virus (HCV) fitness via targeting two sites in the 5'-untranslated region (UTR) of HCV. We used selective 2'-hydroxyl acylation analyzed by primer extension to resolve the HCV 5'-UTR's RNA secondary structure in the presence of miR-122. Nearly all nucleotides in miR-122 are involved in targeting the second site, beyond classic seed base pairings. These additional interactions enhance HCV replication in cell culture. To our knowledge, this is the first biophysical study of this complex to reveal the importance of 'tail' miR-122 nucleotide interactions.

    View details for DOI 10.1128/JVI.06367-11

    View details for Web of Science ID 000298674600056

    View details for PubMedID 22072754

  • Simplified RNA secondary structure mapping by automation of SHAPE data analysis NUCLEIC ACIDS RESEARCH Pang, P. S., Elazar, M., Pham, E. A., Glenn, J. S. 2011; 39 (22)


    SHAPE (Selective 2'-hydroxyl acylation analysed by primer extension) technology has emerged as one of the leading methods of determining RNA secondary structure at the nucleotide level. A significant bottleneck in using SHAPE is the complex and time-consuming data processing that is required. We present here a modified data collection method and a series of algorithms, embodied in a program entitled Fast Analysis of SHAPE traces (FAST), which significantly reduces processing time. We have used this method to resolve the secondary structure of the first ~900 nt of the hepatitis C virus (HCV) genome, including the entire core gene. We have also demonstrated the ability of SHAPE/FAST to detect the binding of a small molecule inhibitor to the HCV internal ribosomal entry site (IRES). In conclusion, FAST allows for high-throughput data processing to match the current high-throughput generation of data possible with SHAPE, reducing the barrier to determining the structure of RNAs of interest.

    View details for DOI 10.1093/nar/gkr773

    View details for Web of Science ID 000298186000004

    View details for PubMedID 21965531

  • Incorporation of multicellular spheroids into 3-D polymeric scaffolds provides an improved tumor model for screening anticancer drugs CANCER SCIENCE Ho, W. J., Pham, E. A., Kim, J. W., Ng, C. W., Kim, J. H., Kamei, D. T., Wu, B. M. 2010; 101 (12): 2637-2643


    Development of cancer therapeutics requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Three-dimensional (3-D) in vitro models have therefore been investigated for drug screening. In this study, we have developed a novel in vitro model in which multicellular aggregates, or spheroids, were incorporated into 3-D porous scaffolds. Drug resistance assays showed that spheroid-seeded scaffolds have much higher drug resistance than monolayer cultures, spheroids on flat substrates, or scaffolds seeded with dispersed cells. Furthermore, spheroid-seeded scaffolds demonstrated higher lactate production leading to acidosis, and higher expression of angiogenic factors. These data suggest that the spheroid-seeded 3-D scaffolds might serve as a useful in vitro system for screening cancer therapeutics.

    View details for DOI 10.1111/j.1349-7006.2010.01723.x

    View details for Web of Science ID 000284321300022

    View details for PubMedID 20849469

  • Modification of the diphenylamine assay for cell quantification in three-dimensional biodegradable polymeric scaffolds. Journal of biomedical materials research. Part B, Applied biomaterials Pham, E. A., Ho, W. J., Kamei, D. T., Wu, B. M. 2010; 92 (2): 499-507


    As three-dimensional (3D) cell culture systems gain popularity in biomedical research, reliable assays for cell proliferation within 3D matrices become more important. Although many cell quantification techniques have been established for cells cultured on nondegradable plastic culture dishes and cells suspended in media, it is becoming increasingly clear that cell quantification after prolonged culture in 3D polymeric scaffolds imposes unique challenges because the added presence of polymeric materials may contribute to background signal via various mechanisms including autofluorescence, diffusion gradients, and sequestering effects. Thus, additional steps are required to ensure complete isolation of cells from the 3D scaffold. The diphenylamine assay isolates cellular DNA, degrades the polymeric matrix materials, and reacts with the DNA to yield a colorimetric response. Thus, we report here a practical modification of the diphenylamine assay and show that the assay quantifies cells in 3D polyester scaffolds reliably and reproducibly as long as the necessary amount of the acidic working reagent is present. Our study also demonstrates that the sensitivity of the assay can be optimized by controlling the dimensions of the sampling volume. Overall, the DPA assay offers an attractive solution for challenges associated with 3D cell quantification.

    View details for DOI 10.1002/jbm.b.31543

    View details for PubMedID 19957351

  • Genetically engineering transferrin to improve its in vitro ability to deliver cytotoxins JOURNAL OF CONTROLLED RELEASE Yoon, D. J., Chu, D. S., Ng, C. W., Pham, E. A., Mason, A. B., Hudson, D. M., Smith, V. C., MacGillivray, R. T., Kamei, D. T. 2009; 133 (3): 178-184


    We previously demonstrated that decreasing the iron release rate of transferrin (Tf), by replacing the synergistic anion carbonate with oxalate, increases its in vitro drug carrier efficacy in HeLa cells. In the current work, the utility of this strategy has been further explored by generating two Tf mutants, K206E/R632A Tf and K206E/K534A Tf, exhibiting different degrees of iron release inhibition. The intracellular trafficking behavior of these Tf mutants has been assessed by measuring their association with HeLa cells. Compared to native Tf, the cellular association of K206E/R632A Tf and K206E/K534A Tf increased by 126 and 250%, respectively. Surface plasmon resonance studies clearly indicate that this increase in cellular association is due to a decrease in the iron release rate and not to differences in binding affinity of the mutants to the Tf receptor (TfR). Diphtheria toxin (DT) conjugates of K206E/R632A Tf and K206E/K534A Tf showed significantly increased cytotoxicity against HeLa cells with IC(50) values of 1.00 pM and 0.93 pM, respectively, compared to a value of 1.73 pM for the native Tf conjugate. Besides further validating our strategy of inhibiting iron release, these Tf mutants provide proof-of-principle that site-directed mutagenesis offers an alternative method for improving the drug carrier efficacy of Tf.

    View details for DOI 10.1016/j.jconrel.2008.10.006

    View details for Web of Science ID 000263700000003

    View details for PubMedID 18992290

  • Inhibition of transferrin iron release increases in vitro drug carrier efficacy JOURNAL OF CONTROLLED RELEASE Lao, B. J., Tsai, W. P., Mashayekhi, F., Pham, E. A., Mason, A. B., Kamei, D. T. 2007; 117 (3): 403-412


    Transferrin (Tf) conjugates of CRM107 are currently being tested in clinical trials for treatment of malignant gliomas. However, the rapid cellular recycling of Tf limits its efficiency as a drug carrier. We have developed a mathematical model of the Tf/TfR trafficking cycle and have identified the Tf iron release rate as a previously unreported factor governing the degree of Tf cellular association. The release of iron from Tf is inhibited by replacing the synergistic carbonate anion with oxalate. Trafficking patterns for oxalate Tf and native Tf are compared by measuring their cellular association with HeLa cells. The amount of Tf associated with the cells is an average of 51% greater for oxalate Tf than for native Tf over a two hour period at Tf concentrations of 0.1 nM and 1 nM. Importantly, diphtheria toxin (DT) conjugates of oxalate Tf are more cytotoxic against HeLa cells than conjugates of native Tf. Conjugate IC(50) values were determined to be 0.06 nM for the oxalate Tf conjugate vs. 0.22 nM for the native Tf conjugate. Thus, we show that inhibition of Tf iron release improves the efficacy of Tf as a drug carrier through increased association with cells expressing TfR.

    View details for DOI 10.1016/j.jconrel.2006.12.001

    View details for Web of Science ID 000244928100013

    View details for PubMedID 17239470