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Abstract:

Cancer-Targeting Tides (CTTs) have enabled the modular design and development of precision nanomedicines in the diagnosis and treatment of cancer. At the forefront of their utility are solid-phase synthesis methods that have facilitated the rapid, scale-up production of synthetic CTTs, such as oligonucleotides and peptides, for medicinal chemistry applications. Of specific interest, are short-interfering RNA (siRNA), that have silenced oncogenic mRNA expression leading to cancer cell death through the RNA interference (RNAi) pathway. Our research is focused on synthetic siRNAs that have been designed to target and silence the expression of the oncogenic Glucose Regulated Proteins (GRPs) that have been classified as clinically relevant therapeutic targets in cancer detection and therapy. In order to potentiate siRNA therapeutic efficacy, we have developed branch and hyperbranch siRNA that self-assembled into higher-ordered nanostructures which silenced multiple GRPs in synergy, thereby enhancing their anti-cancer effects. We have also expanded the scope of synthetic siRNAs by chemical ligation of biologically active probes (fluorescent labels, lipid appendages and metal nanoparticles) for enhanced detection, uptake and RNAi activity in cancer cells. Similarly, we have designed and developed de novo synthetic peptides for anti-cancer utility. This specific class of synthetic biologicals has enabled molecular cancer biology investigations via the cell targeting/penetrating peptides, selected for oligonucleotide condensation and delivery within cancer cell lines for gene therapy applications. Our work has also led to the discovery of a new class of immunostimulatory peptides, capable of activation of Natural Killer (NK) cells and immunotoxicity towards targeted tumors in a mechanism of action reminiscent of the targeting and activating functions of antibodies. This cancer immunotherapy approach sheds important insights into the development of synthetic antibody mimics as well as the rational design and development of synthetic peptide vaccines. This presentation will thus serve to highlight the importance of synthetic biologicals such as the CTTs for clinical oncology research.

Bio:

Dr. David Sabatino was born and raised in Montreal, Quebec Canada where he completed his B.Sc. (2002) and Ph.D. (2007) at 成人VR视频 in the area of nucleic acid biochemistry under the supervision of Professor Masad J. Damha. As a research fellow, he completed his post-doctoral training with Professor William D. Lubell at l鈥橴niversit茅 de Montr茅al in 2010 developing new methods in the chemical synthesis of peptide mimics.

Dr. Sabatino was then appointed as faculty in the Department of Chemistry and Biochemistry at Seton Hall University and also held a joint appointment in the Department of Medical Sciences at the Hackensack-Meridian School of Medicine where he was engaged in multiple biomedical research collaborations. In January 2022, Dr. Sabatino joined the faculty at Carleton University where he is currently

Dr. Sabatino鈥檚 research interests span the areas of nucleic acid and peptide chemical biology. Dr. Sabatino鈥檚 research aims to explore the influence of structural modification on the anti-cancer activity of biological molecules for drug discovery applications. Dr. Sabatino is co-author of more than 40 peer-reviewed scientific publications, conference proceedings, patents and a book chapter. Dr. Sabatino has also co-authored more than 60 conference presentations in regional, national and international meetings. Dr. Sabatino has also received funding support from the federal government (NIH/NCI) for research related to the development of anti-cancer treatment strategies. His research accomplishments have been recognized and awarded, with being most recently nominated Researcher of the Year in 2019 at Seton Hall University. Dr. Sabatino is also acting topics editor of Molecules-open access journal, as well as a member of the Chemical Biology steering committee at the New York and New Jersey Academy of Sciences and is a contributing member of several other scientific associations.