Day 1 :
National University of Singapore, Singapore
Time : 09:30-10:15
After completion of his postdoctoral training at University of Texas MD Anderson Cancer Center, Dr. Gautam Sethi joined Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore in 2008 as an Assistant Professor and was promoted to Associate Professor in 2015. The focus of his research over the past few years has been to elucidate the mechanism (s) of activation of oncogenic transcription factors such as NF-kB/STAT3 by carcinogens and inflammatory agents and the identification of novel inhibitors of these proteins for prevention of and therapy for cancer. The findings of his research work have so far resulted in more than two hundred scientific publications in high impact factor peer reviewed journals (with h index = 68) and several international awards. He currently serves as an Academic Editor for PLOS, editorial board member of Scientific Reports, Cancer Letters, Pharmacological Research, BMC Cancer, Frontiers in Pharmacology, Frontiers in Oncology, Journal of Natural Products in Cancer Prevention and Therapy, and ad-hoc reviewer for several other prestigious international journals.
Signal Transducers and Activators of Transcription (STATs) comprise an important class of transcription factors that have been implicated in a wide variety of essential cellular functions related to proliferation, survival, and angiogenesis. Among various STAT members, STAT3 is frequently overexpressed in tumor cells as well as tissue samples, and regulates the expression of numerous oncogenic genes controlling the growth and metastasis of tumor cells. I will briefly discuss the importance of STAT3 as a potential target for cancer therapy and also provide novel insights into various classes of existing pharmacological inhibitors of this transcription factor that can be potentially developed as anti-cancer drugs.
Duke-NUS Medical School, Singapore
Keynote: The effect of cross-reactive antibodies on immunogenicity of live-attenuated vaccine: A systems approach
Time : 10:15-11:00
Chan Kuan Rong is an Immunologist, specializing in elucidating the role of antibodies in dengue virus infection. He is a Senior Research Fellow in the laboratory of Professor Ooi Eng Eong in the Program of Emerging Infectious Diseases. During his doctoral studies, he identified two co-receptors, Fc-gamma receptor IIB and leukocyte immunoglobulin-like receptor B1, that are involved in antibody-mediated dengue virus neutralization and infection enhancement, respectively. His Postdoctoral research focuses on exploring the use of cross-reactive antibodies to boost efficacy of live vaccines, with the ultimate aim to develop vaccines that are safe and immunogenic.
Live-attenuated vaccines (LAV) are reputed to be the most cost-effective tools for controlling epidemics. With increasing disease outbreaks caused by virus infections, vaccines will have to be delivered to both adults and children, who may have pre-existing cross-reactive antibodies due to previous exposure with an antigenically related virus strain. We and others have shown in vitro that cross-reactive antibodies can improve vaccine efficacy by enhancing LAV infection in Fc gamma-receptor (FcgR) expressing antigen-presenting cells (APCs), a process known as antibody-dependent enhancement (ADE). However, the relevance and occurrence of ADE has yet to be demonstrated clinically. We conducted an open-label trial where subjects are sequentially immunized with the inactivated Japanese Encephalitis (JE) vaccine (Ixiaro®) followed by a live-attenuated yellow fever (YF) vaccine (Stamaril®). To generate a range of cross-reactive antibodies concentrations, subjects were divided into 3 groups, where they were given JE and YF vaccines at either 1-month (Group 1), 4-months (Group 2) or 9-months (Group 3) apart. Group 4 served as a control where only YF vaccine was administered. A specific range of cross-reactive antibodies from JE vaccination enhanced YF immunogenicity, which is consistent with in vitro ADE of virus infection of FcgR-expressing APCs. We further employed a systems biology approach encompassing viremia, transcriptomics, metabolomics and cytokine profiling to explain the molecular basis behind antibody-enhanced YF vaccination. Besides signatures related to increased immunogenicity, we additionally investigated the molecular basis behind reactogenicity. We observed an up-regulation of the innate immune pathways at day 1 post-YF vaccination, and this up-regulation correlated with occurrence of AE. Our findings reveal that the innate immune response can be a double-edge sword, where an early induction results in AE and later induction engenders robust immunity.
University of Cambridge, UK
Time : 11:15-12:15
Dr Rameen Shakur is a clinician scientist in Cardiology and the Wellcome trust clinical fellow for the University of Cambridge. Dr Shakur trained at Cambridge, Oxford and Edinburgh University medical schools for his clinical training, finally practising in Cardiology in London, UK. He completed his PhD in modelling inherited cardiac diseases at the Wellcome Trust Sanger centre and the Laboratory of Regenerative Medicine at the University of Cambridge. He was also Cambridge BRC fellow at George Church's lab at Harvard medical School and a previous Churchill fellow at Harvard University and Mayo medical school, Rochester and Peter Kirk fellow at ehe Karolinska institute Sweden. He is the author of 4 text books and numerous papers.
Hypertrophic Cardiomyopathy (HCM) was the first of the cardiomyopathies to be attributed a genetic etiology. It is also considered to be one of the commonest hereditary cardiac disorders with a prevalence of about 1:500 in young adults. Yet, after 25 years although much has been gained in unraveling the genetic basis for HCM; clinical management of these patients is still based on symptom control and the prophylactic implantation of internal cardio defibrillators (ICD) for the prevention of fatal cardiac arrhythmias. Risk stratifying those patients who are most likely to benefit from device therapy given some mutations have a higher propensity for sudden cardiac death than others has proved difficult. However, the potential for pharmacological therapy in such cases has often not been considered given a lack of understanding of the inherent biological systems perturbed as a result of these underlying genetic changes, we put forward a platform to better understand the mechanism of action of some of the HCM phenotypes using an in silico then in vitro model which attempts to define the structural and physical characteristics of mutations within the confines of clinical datasets to define prognostic implications of sequences. This was then integrated “omics” model and later verified experimentally, potential drugs were used which could be repurposed to target some of the main pathways shown to be perturbed in this process. This represents a possible methodology for which in cardiovascular and inherited cardiac disorders may aid the clinical potentials for personalized therapeutics.