Plenary Lecture

Biochemical Signalling Pathways Controlling Biological Responses of Human Myeloid Cells and Their Highly Specific Targeting Using Gold Nanoparticle-Based Biologically Active Conjugates

Professor Vadim V. Sumbayev
Medway School of Pharmacy
University of Kent
United Kingdom

Abstract: Human hematopoietic cells of myeloid lineage control crucial normal and pathophysiological reactions of human immune system. They are responsible for recognition of pathogen-associated molecular patterns followed by the inflammatory/innate immune responses to pathogens. Antigen presentation and promotion of lymphocyte-dependent adaptive immunity is also a responsibility of myeloid cells. On the other hand, allergic reactions are induced by the effector cells (mast cells and basophils) which belong to the myeloid lineage. Furthermore, immature myeloid cells could undergo malignant transformation causing acute myeloid leukaemia, which is a serious medical burden all over the world.
Our research demonstrated that all these kinds of responses become possible when the cells are properly adapted to stress caused by these reactions. The process of myeloid cell adaptation to pro-inflammatory/pro-leukaemic stress is controlled by hypoxia-inducible factor 1 (HIF-1) transcription complex which has a number of target genes encoding proteins/enzymes responsible for angiogenesis, glycolysis and cell adhesion.
HIF-1 activation is controlled via differential mechanisms including redox-dependent pathways inhibiting degradation of its alpha subunit by prolyl-hydroxylation, MAP kinase pathways and biosynthetic mechanism (driven by mammalian target of rapamycin – mTOR)
. We are currently using a new approach for highly specific targeting of human myeloid cells by functionalised gold nanoconjugates generated on the basis of citrate-stabilised gold nanoparticles. This allowed delivery of pharmacological inhibitors (rapamycin and ascomycin) into the target cells – human myeloid leukaemia monocytes and primary human basophils. Delivered drugs were capable of inducing the necessary functional effects.

Brief Biography of the Speaker: I obtained my PhD degree in Biochemistry in 1999 in Palladin Institute of Biochemistry NAS of UKraine. Then worked as assistant/associate professor at the Department of Biochemistry, Mechnikoff Odessa National University. In 2001 I obtained a highly competitive Humboldt Research Fellowship and moved to Germany (University of Kaiserslautern). Upon completion of my fellowship I spent three years in Aarhus (Denmark) working as assistant professor at the Interdisciplinary Nanoscience Centre, University of Aarhus. In December 2006 I joined Medway School of Pharmacy as a lecturer in Biochemistry.

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