Bio

Bio


For the past 4 years as a post-doctorate fellow at the Department of Radiation Oncology, Stanford University, I have dedicated my work on the development of primary cancer and metastatic tumor-mouse models for the purpose of investigating immune cell migration, early detection of disease, and clinically relevant therapy combining radiation with novel drugs. My training as a doctorate candidate and during my brief post-doctorate appointment in the Department of Radiation Oncology, Oxford University UK has equipped me with a deep understanding of the molecularly targeted in vivo imaging with the use of contrast agents for early detection of metastasis. As a physics undergraduate and graduate student at the Department of Physics, Liverpool University UK, I have developed deep knowledge in all types of radiation and their implication in the entire spectrum of imaging modalities and medical radiation treatment.

Honors & Awards


  • Invited presentation, Oxford Cancer Imaging Center Retreat (2013, 2014)
  • Invited presentation, Oxford Institute Metastasis Symposium (2014)
  • Poster Prize, Aegean Conferences - 3rd International Conference for Tumour Microenvironment and Cellular Stress (2014)
  • Recognition of excellent research, Aegean Conferences - 12th International Conference on Complement Therapeutics (2019)

Professional Education


  • Doctor of Philosophy, University of Oxford (2015)
  • Master of Science, University of Oxford (2010)
  • Master of Science, University Of Liverpool (2009)
  • Bachelor of Science, University Of Liverpool (2008)
  • Associate in Engineering, IIEK Neapoleos, Greece (2000)

Stanford Advisors


Publications

All Publications


  • Theranostic nanoparticles enhance the response of glioblastomas to radiation Nanotheranostics Wu, W., Klockow, J. L., Mohanty, S., Ku, K. S., Daldrup-Link, H. E. 2019; 3(4) (299-310)

    View details for DOI 10.7150/ntno.35342

  • The tumour microenvironment links complement system dysregulation and hypoxic signalling. The British journal of radiology Olcina, M. M., Kim, R. K., Melemenidis, S., Graves, E. E., Giaccia, A. J. 2018: 20180069

    Abstract

    The complement system is an innate immune pathway typically thought of as part of the first line of defence against "non-self" species. In the context of cancer, complement has been described to have an active role in facilitating cancer-associated processes such as increased proliferation, angiogenesis and migration. Several cellular members of the tumour microenvironment express and/or produce complement proteins locally, including tumour cells. Dysregulation of the complement system has been reported in numerous tumours and increased expression of complement activation fragments in cancer patient specimens correlates with poor patient prognosis. Importantly, genetic or pharmacological targeting of complement has been shown to reduce tumour growth in several cancer preclinical models, suggesting that complement could be an attractive therapeutic target. Hypoxia (low oxygen) is frequently found in solid tumours and has a profound biological impact on cellular and non-cellular components of the tumour microenvironment. In this review, we focus on hypoxia since this is a prevailing feature of the tumour microenvironment that, like increased complement, is typically associated with poor prognosis. Furthermore, interesting links between hypoxia and complement have been recently proposed but never collectively reviewed. Here, we explore how hypoxia alters regulation of complement proteins in different cellular components of the tumour microenvironment, as well as the downstream biological consequences of this regulation.

    View details for PubMedID 29544344

  • Macrophages Promote Circulating Tumor Cell-Mediated Local Recurrence Following Radiation Therapy in Immunosuppressed Patients. Cancer research Rafat, M., Aguilera, T. A., Vilalta, M., Bronsart, L. L., Soto, L. A., von Eyben, R., Golla, M. A., Ahrari, Y., Melemenidis, S., Afghahi, A., Jenkins, M. J., Kurian, A. W., Horst, K., Giaccia, A. J., Graves, E. E. 2018

    Abstract

    Although radiation therapy (RT) decreases the incidence of locoregional recurrence in breast cancer, patients with triple-negative breast cancer (TNBC) have increased risk of local recurrence following breast-conserving therapy (BCT). The relationship between RT and local recurrence is unknown. Here we tested the hypothesis that recurrence in some instances is due to the attraction of circulating tumor cells to irradiated tissues. To evaluate the effect of absolute lymphocyte count on local recurrence after RT in TNBC patients, we analyzed radiation effects on tumor and immune cell recruitment to tissues in an orthotopic breast cancer model. Recurrent patients exhibited a prolonged low absolute lymphocyte count when compared to non-recurrent patients following RT. Recruitment of tumor cells to irradiated normal tissues was enhanced in the absence of CD8+ T cells. Macrophages (CD11b+F480+) preceded tumor cell infiltration and were recruited to tissues following RT. Tumor cell recruitment was mitigated by inhibiting macrophage infiltration using maraviroc, an FDA-approved CCR5 receptor antagonist. Our work poses the intriguing possibility that excessive macrophage infiltration in the absence of lymphocytes promotes local recurrence after RT. This combination thus defines a high-risk group of TNBC patients.

    View details for PubMedID 29880480

  • Molecular magnetic resonance imaging of angiogenesis in vivo using polyvalent cyclic RGD-iron oxide microparticle conjugates. Theranostics Melemenidis, S., Jefferson, A., Ruparelia, N., Akhtar, A. M., Xie, J., Allen, D., Hamilton, A., Larkin, J. R., Perez-Balderas, F., Smart, S. C., Muschel, R. J., Chen, X., Sibson, N. R., Choudhury, R. P. 2015; 5 (5): 515–29

    Abstract

    Angiogenesis is an essential component of tumour growth and, consequently, an important target both therapeutically and diagnostically. The cell adhesion molecule α(v)β(3) integrin is a specific marker of angiogenic vessels and the most prevalent vascular integrin that binds the amino acid sequence arginine-glycine-aspartic acid (RGD). Previous studies using RGD-targeted nanoparticles (20-50 nm diameter) of iron oxide (NPIO) for magnetic resonance imaging (MRI) of tumour angiogenesis, have identified a number of limitations, including non-specific extravasation, long blood half-life (reducing specific contrast) and low targeting valency. The aim of this study, therefore, was to determine whether conjugation of a cyclic RGD variant [c(RGDyK)], with enhanced affinity for α(v)β(3), to microparticles of iron oxide (MPIO) would provide a more sensitive contrast agent for imaging of angiogenic tumour vessels. Cyclic RGD [c(RGDyK)] and RAD [c(RADyK)] based peptides were coupled to 2.8 μm MPIO, and binding efficacy tested both in vitro and in vivo. Significantly greater specific binding of c(RGDyK)-MPIO to S-nitroso-n-acetylpenicillamine (SNAP)-stimulated human umbilical vein endothelial cells in vitro than PBS-treated cells was demonstrated under both static (14-fold increase; P < 0.001) and flow (44-fold increase; P < 0.001) conditions. Subsequently, mice bearing subcutaneous colorectal (MC38) or melanoma (B16F10) derived tumours underwent in vivo MRI pre- and post-intravenous administration of c(RGDyK)-MPIO or c(RADyK)-MPIO. A significantly greater volume of MPIO-induced hypointensities were found in c(RGDyK)-MPIO injected compared to c(RADyK)-MPIO injected mice, in both tumour models (P < 0.05). Similarly, administration of c(RGDyK)-MPIO induced a greater reduction in mean tumour T(2)* relaxation times than the control agent in both tumour models (melanoma P < 0.001; colorectal P < 0.0001). Correspondingly, MPIO density per tumour volume assessed immunohistochemically was significantly greater for c(RGDyK)-MPIO than c(RADyK)-MPIO injected animals, in both melanoma (P < 0.05) and colorectal (P < 0.0005) tumours. In both cases, binding of c(RGDyK)-MPIO co-localised with α(v)β(3) expression. Comparison of RGD-targeted and dynamic contrast enhanced (DCE) MRI assessment of tumour perfusion indicated sensitivity to different vascular features. This study demonstrates specific binding of c(RGDyK)-MPIO to α(v)β(3) expressing neo-vessels, with marked and quantifiable contrast and rapid clearance of unbound particles from the blood circulation compared to NPIO. Combination of this molecular MRI approach with conventional DCE MRI will enable integrated molecular, anatomical and perfusion tumour imaging.

    View details for DOI 10.7150/thno.10319

    View details for PubMedID 25767618

    View details for PubMedCentralID PMC4350013

Latest information on COVID-19