Honors & Awards


  • NSF Graduate Student Fellowship, National Science Foundation (9/2016-8/2018)

Education & Certifications


  • Master of Science, Stanford University, BIOE-MS (2016)
  • BSE, University of Pennsylvania, Bioengineering (2014)

Lab Affiliations


All Publications


  • Nanoparticles Functionalized with Collagenase Exhibit Improved Tumor Accumulation in a Murine Xenograft Model Particle Murty, S., Gilliland, T., Qiao, P., Tabtieng, T., Higbee, E., Al Zaki, A., Pure, E., Tsourkas, A. 2014; 31 (12): 1307-1312
  • Theranostic Application of Mixed Gold and Superparamagnetic Iron Oxide Nanoparticle Micelles in Glioblastoma Multiforme Journal of Biomedical Technology Sun, L., Joh, D. Y., Al-Zaki, A., Stangl, M., Murty, S., et al 2016; 12 (2): 347-356
  • AshwaMAX and Withaferin A inhibits gliomas in cellular and murine orthotopic models JOURNAL OF NEURO-ONCOLOGY Chang, E., Pohling, C., Natarajan, A., Witney, T. H., Kaur, J., Xu, L., Gowrishankar, G., D'Souza, A. L., Murty, S., Schick, S., Chen, L., Wu, N., Khaw, P., Mischel, P., Abbasi, T., Usmani, S., Mallick, P., Gambhir, S. S. 2016; 126 (2): 253-264

    Abstract

    Glioblastoma multiforme (GBM) is an aggressive, malignant cancer Johnson and O'Neill (J Neurooncol 107: 359-364, 2012). An extract from the winter cherry plant (Withania somnifera ), AshwaMAX, is concentrated (4.3 %) for Withaferin A; a steroidal lactone that inhibits cancer cells Vanden Berghe et al. (Cancer Epidemiol Biomark Prev 23: 1985-1996, 2014). We hypothesized that AshwaMAX could treat GBM and that bioluminescence imaging (BLI) could track oral therapy in orthotopic murine models of glioblastoma. Human parietal-cortical glioblastoma cells (GBM2, GBM39) were isolated from primary tumors while U87-MG was obtained commercially. GBM2 was transduced with lentiviral vectors that express Green Fluorescent Protein (GFP)/firefly luciferase fusion proteins. Mutational, expression and proliferative status of GBMs were studied. Intracranial xenografts of glioblastomas were grown in the right frontal regions of female, nude mice (n = 3-5 per experiment). Tumor growth was followed through BLI. Neurosphere cultures (U87-MG, GBM2 and GBM39) were inhibited by AshwaMAX at IC50 of 1.4, 0.19 and 0.22 µM equivalent respectively and by Withaferin A with IC50 of 0.31, 0.28 and 0.25 µM respectively. Oral gavage, every other day, of AshwaMAX (40 mg/kg per day) significantly reduced bioluminescence signal (n = 3 mice, p < 0.02, four parameter non-linear regression analysis) in preclinical models. After 30 days of treatment, bioluminescent signal increased suggesting onset of resistance. BLI signal for control, vehicle-treated mice increased and then plateaued. Bioluminescent imaging revealed diffuse growth of GBM2 xenografts. With AshwaMAX, GBM neurospheres collapsed at nanomolar concentrations. Oral treatment studies on murine models confirmed that AshwaMAX is effective against orthotopic GBM. AshwaMAX is thus a promising candidate for future clinical translation in patients with GBM.

    View details for DOI 10.1007/s11060-015-1972-1

    View details for Web of Science ID 000368728300005

  • Theranostic Gold Nanoparticles Modified for Durable Systemic Circulation Effectively and Safely Enhance the Radiation Therapy of Human Sarcoma Cells and Tumors TRANSLATIONAL ONCOLOGY Joh, D. Y., Kao, G. D., Murty, S., Stangl, M., Sun, L., Al Zaki, A., Xu, X., Hahn, S. M., Tsourkas, A., Dorsey, J. F. 2013; 6 (6): 722-U363

    Abstract

    Radiation therapy (RT) is an integral component of the treatment of many sarcomas and relies on accurate targeting of tumor tissue. Despite conventional treatment planning and RT, local failure rates of 10% to 28% at 5 years have been reported for locally advanced, unresectable sarcomas, due in part to limitations in the cumulative RT dose that may be safely delivered. We describe studies of the potential usefulness of gold nanoparticles modified for durable systemic circulation (through polyethylene glycosylation; hereinafter "P-GNPs") as adjuvants for RT of sarcomas. In studies of two human sarcoma-derived cell lines, P-GNP in conjunction with RT caused increased unrepaired DNA damage, reflected by approximately 1.61-fold increase in γ-H2AX (histone phosphorylated on Ser(139)) foci density compared with RT alone. The combined RT and P-GNP also led to significantly reduced clonogenic survival of tumor cells, compared to RT alone, with dose-enhancement ratios of 1.08 to 1.16. In mice engrafted with human sarcoma tumor cells, the P-GNP selectively accumulated in the tumor and enabled durable imaging, potentially aiding radiosensitization as well as treatment planning. Mice pretreated with P-GNP before targeted RT of their tumors exhibited significantly improved tumor regression and overall survival, with long-term survival in one third of mice in this treatment group compared to none with RT only. Interestingly, prior RT of sarcoma tumors increased subsequent extravasation and in-tumor deposition of P-GNP. These results together suggest P-GNP may be integrated into the RT of sarcomas, potentially improving target imaging and radiosensitization of tumor while minimizing dose to normal tissues.

    View details for DOI 10.1593/tlo.13433

    View details for Web of Science ID 000330342400014

    View details for PubMedID 24466375

    View details for PubMedCentralID PMC3890707

  • Selective Targeting of Brain Tumors with Gold Nanoparticle-Induced Radiosensitization PLOS ONE Joh, D. Y., Sun, L., Stangl, M., Al Zaki, A., Murty, S., Santoiemma, P. P., Davis, J. J., Baumann, B. C., Alonso-Basanta, M., Bhang, D., Kao, G. D., Tsourkas, A., Dorsey, J. F. 2013; 8 (4)

    Abstract

    Successful treatment of brain tumors such as glioblastoma multiforme (GBM) is limited in large part by the cumulative dose of Radiation Therapy (RT) that can be safely given and the blood-brain barrier (BBB), which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs). GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ~1.3). Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature.

    View details for DOI 10.1371/journal.pone.0062425

    View details for Web of Science ID 000319077300056

    View details for PubMedID 23638079

    View details for PubMedCentralID PMC3640092