Day 2 :
- Personalised Medicine | Biopharmaceutics | Pharmacotherapy | Pharmacological Sciences | Biomedicine
Location: Yoshino
Session Introduction
Duncan Ayers
University of Malta, Malta
Title: Non-coding RNA involvement in cancer: The case for Neuroblastoma
Biography:
Dr. Duncan Ayers has completed his PhD in Translational Medicine from The University of Manchester (UK) in 2011 and is currently continuing his senior post-doctoral research at the University of Malta (CMMB). Dr. Ayers’ researchfocuses mainly on non-coding RNA biomarker discovery and therapeutic applications for paediatric cancers such as neuroblastoma. Other research interests include the influences of gene, micro RNA (miRNA) and other non-coding RNA expression profiles in the development of human disease conditions, high throughput semi-/quantitative gene (or miRNA, lncRNA, etc.) analytical techniques such as RT- qPCR, microarray platform utilization and the development of nanoparticle – based drug delivery systems for RNA interference -based therapeutics in cancer. Dr. Ayers’ research has been published / presented in over 40 reputed peer -reviewed journal papers and international meetings, together with contributing to five book publications.
Abstract:
Neuroblastoma (NB) is a paediatric tumour afflicting the developing neurons and typically manifests itself in children between 1-5 years of age. The prognosis for NB is in the region of 50%, with this value lowering to 15% in cases of relapsed NB. Furthermore, NB development and clinical manifestation depends on multiple molecular networks’ dysreguated activities, including at the genomic and transcriptomic levels.
The introduction of RNA interference (RNAi) technology in the 1990s gave a new insight into factors acting on oncogene regulatory processes. Noncoding sequences of the transcriptome have been in fact found to play major roles in gene regulation. MiRNAs are noncoding ribonucleic acids of approximately 22 base pairs in size originating within the cell and function as chief regulators in gene expression.
Long non-coding RNAs (lncRNAs) are a novel class of approximately 15,000 – 20,000 non -protein coding RNAs, having a base length of over 200 nucleotides and are the result of RNA Polymerase II activities. Long non-coding RNAs have only just recently been identified to play a major role in gene regulatory pathways for a wide spectrum of human disease conditions, including multiple cancer models such as NB.
Consequently, our group has played a part in discovering and developing novel non-coding RNA biomarkers deemed to have direct influence on NB tumourigenesis and other tumour characteristics, including conventional therapy chemoresistance.
R Manjunatha Kini
National University of Singapore, Singapore
Title: Natriuretic peptide analogs with vasodilatory or renal activities: personalized care of heart failure patients
Biography:
Manjunatha Kini conducts basic and applied research on snake venoms and saliva of blood-feeding animals, both contain pharmacologically-active proteins. He is an accomplished biochemist and established world leader in the field of toxins as well as in blood clotting (thrombosis and hemostasis). His main research focus is "From Toxins to Therapeutics", where he identifies novel bioactive proteins from venoms or saliva, determines their modes of action, and designs potential drug-leads based on their structure. Venom toxins target cardiovascular and neuromuscular systems. He has published 240 research publications including 182 original articles, 40 reviews and 18 book chapters. In addition, he also filed 50 patent applications. He edited two monographs “Venom Phospholipase A2 Enzymes: Structure, Function and Mechanism” (Sole editor, 1997, John Wiley, England) and “Toxins and Hemostasis: From Bench to Bedside” (Chief Editor, 2010, Springer, The Netherlands). He also edited five special issues for various journals.
Abstract:
Natriuretic peptides (NPs) are potent vasoactive hormones, which maintain pressure-volume homoeostasis. All three isoforms of mammalian NPs, namely ANP, BNP and CNP have a conserved 17-residue ring but with highly variable C-terminal extensions. These peptides confer their functions through binding to three membrane-bound NP receptors (NPRs). ANP and BNP bind to NPR-A, whereas CNP binds to NPR-B, both Guanylyl Cyclase (GC) linked receptors. NPR-A and NPR-B undergo conformational change upon respective NP binding and lead to the production of intracellular cGMP. Snake venom NPs, although have the conserved NP-ring, exhibit distinct biological activity compared with mammalian NPs due to subtle changes in their sequences. We recently identified a new NP from Krait Venom (KNP), with an unusual 38-residue long C-terminal tail, which has a propensity to form a α-helix. Deletion mutant studies have revealed the presence of two pharmacophores in KNP, namely ring and helix. These functional segments induced vasodilation through orthogonal pathways. Ring, like a classical NP, elevates intracellular cGMP levels through activation of NPR-A with a 10-fold lower potency compared to ANP, while helix uses NO-dependent mechanisms. By systematic structure-function studies, we were able to delineate the amino acid residues that determine vasodilatory and diuretic functions. Using the new knowledge, development of two classes of human Natriuretic Peptide Analogues (NPAs); one group of NPAs with only vasodilatory effects without diuretic function and the second group with only diuretic effects without vasodilatory function was done. Such distinct classes of NPAs will be useful in the treatment of distinct classes of ADHF (Acute Decompensated Heart Failure) patients.