Day 3 :
- Track 10: Next Generation Sequencing Services
Track 11: Pharmacogenomics Past, Present and Future
Track 12: Plant & Ecological Genomics
Subbu Apparsundaram completed his doctorate in Pharmacology at the University of Houston and post-doctoral work in neuropharmacology at the Vanderbilt University. He was a faculty at the University of Kentucky and was a senior scientist at Roche Pharmaceuticals. Currently, he is Chief Science Officer at V ClinBio. He has wide experience in neuropharmacology and is focused in the application of translational research for advancing biomarker discovery, diagnostics development and personalized medicine in multiple therapeutic areas. He has more than 40 peer reviewed publications.
The promise of personalized medicine in providing the most effective and safe therapeutics to specific subpopulation of patients relies on the proper diagnosis of the disease and understanding of pharmacogenomics of pharmacological agents and the causes of variations of drug effects in different patient populations. Variations in drug efficacy and safety have been associated to differences in disease pathology, pharmacokinetics and pharmacodynamics actions of agents. Recent advances in personalized / stratified medicine are occurring mainly due to the completion of the human genome, rapid growth in the use of next-generation sequencing technologies and application of advanced techniques for identifying novel biomarkers in understanding disease pathology and response to therapeutic agents or other interventions. This talk will provide an overview of biomarkers in CNS disorders, and the integration of different types of biomarkers in understanding disease pathology, in drug discovery and development process with particular focus in CNS disorders. Pharmacokinetic, pharmacodynamic and pharmacogenomic biomarkers that are used to optimize treatment outcomes will be discussed. Particular attempts to understand genetic variations driving susceptibility to CNS disorders in different patient populations across geographical regions and drug efficacy and therapeutic efficacy will be reviewed.
North Carolina State University, USA
Title: Using DNA copy number aberrations in naturally occurring canine cancers to identify candidate drivers of carcinogenesis
Time : 10:20-10:40
Daniel Rotroff has completed his MSPH and his Ph.D. from the University of North Carolina at Chapel Hill and is currently a postdoctoral research scholar at North Carolina State University in the Department of Statistics. His graduate work was conducted within the ToxCast project at the National Center for Computational Toxicology at the US EPA and focused on predictive modeling of the estrogen receptor signaling pathway. He is currently focused on association mapping and predictive modeling for a wide range of pharmacogenomics applications.
There are approximately 78 million domestic dogs residing in the USA. Cancer is one of the leading causes of death for domestic dogs, with popular breeds such as golden retrievers, Labrador retrievers and boxers, succumbing to cancer with frequencies of 50, 34 and 44%, respectively. Because canines exhibit a wide variety of spontaneous cancers that share clinicopathologic features with humans, we have a unique opportunity for comparative analysis of naturally occurring cancers toward advancing treatment strategies in both species. Furthermore, the recent development of a high-quality canine genome sequence assembly has opened the door for researchers to identify key drivers of disease that may impact both canine and human patients. We have developed tumor-associated genomic DNA copy number aberration profiles for 75 canine hemangiosarcomas and more than 200 canine leukemias and lymphosarcomas using an oligonucleotide array comparative genomic hybridization (oaCGH) platform. Using a variety of bioinformatic approaches we have mapped canine genes to available human homologues for pathway-based analyses, identified putative drivers of carcinogenesis, and have identified genes that may be useful as diagnostic tools for characterizing leukemia subtypes. Overall, these results demonstrate the potential for using spontaneously occurring canine cancers to improve diagnoses and develop novel therapies for both dogs and humans.
Virginia Bioinformatics Institute, Virginia Tech, USA
Time : 10:20-11:00
Hehuang David Xie graduated from the University of Iowa with Ph.D. in genetics and a master degree in computer science in 2003. After his graduate studies, Dr. Xie received his postdoctoral training in the field of bioinformatics at The University of Iowa and The University of Minnesota. In 2005, Dr. Xie joined the Cancer Biology and Epigenomics Program, Children’s Memorial Research Center; Department of Pediatrics, Northwestern University as a research faculty. Currently, Dr. Xie is an associate professor at the Virginia Bioinformatics Institute.
Decoding epigenome is a new and growing field of post-genomic research. With the advance in high-throughput sequencing technologies, large scale omics data including methylomes have been accumulated rapidly in the past few years. However, the cross-talk among epigenome, transcriptome and transcription factor binding remain largely unexplored. As an epigenetic on/off switch, DNA methylation plays essential roles in controlling chromatin configuration and gene expression. It has been recognized as an essential mechanism allowing genetically identical cells to exhibit distinct phenotypes. Recently, we developed genome-wide hairpin bisulfite sequencing technology and a series of computational tools to decode DNA methylation patterns. Integrative “omics” data analysis has been performed to understand the regulatory mechanisms underlying the DNA methylation dynamics. The novel insights gained from omics data analyses for stem cells and differentiated tissues will be discussed.
Northwest University, China
Title: Genetic polymorphisms of pharmacogenomic VIP variants in the various ethnic minority from China
Time : 11:20-11:40
Huijuan Wang has graduated from Northwest University of China and received her PhD degree in Biochemistry and Molecular biology. Since 2011, she was recruited as a Teaching Staff by College of Life Science, Northwest University mainly focuses on the clinical application of pharmacogenomics fi ndings in disease treatment especially cancers including development of genotyping methods and reagents for drug-related biomarkers and mechanic study of cancer-related biomarkers. Besides, lots of efforts are also dedicated on the study of the molecular mechanism underlying the resistance of anticancer drugs such as BRAF inhibitors and endocrine therapy.
Background: It is well-established that the differences among ethnic groups in drug response mainly lie in the genetic diversity of pharmacogenes. A number of genes or variants which play a crucial role in drug response have been summarized as the Very Important Pharmacogenes(VIP) by PharmGKB database. And to clarify the polymorphic distribution of the VIP genes in different ethnic groups will aid to the personalized medicine in specific populations. Methods: In the present study, we genotyped 85 pharmacogenomic VIP variants in the Kyrgyz population, Lhoba population, Uygur population, Deng people, Mongol nationality, Sherpa population, and Tibetanin Northwestern China and compared our data with other four major human populations including Han Chinese in Beijing, China (CHB), the Japanese in Tokyo, Japan (JPT), a northern and western Europe population (CEU), and the Yoruba in Ibadan, Nigeria (YRI). 85 pharmacogenomic VIP variants were genotyped in 700 Chinese subjects consisting of 100 Kyrgyz, 100 Lhoba, 100 Uygur, 100 Deng, 100 Mongol, 100 Sherpa and 100 Tibetan by Mass ARRAY platform. Genetic frequencies of these variants, haplotype distribution and comparison with those in four Hap Map populations including Han Chinese in Beijing, China (CHB), the Japanese in Tokyo, Japan (JPT), a northern and western Europe population (CEU), and the Yoruba in Ibadan, Nigeria (YRI) were analyzed. Results: We found there were three the selected VIP variant genotype frequencies in these ethnic minorities which differed from thoseof the CHB, JPT and CEU, respectively (p < 0.05/85), particularly differed from the YRI.These three sites located in the PTGS2 gene, ADH family ADH1B genes, VDR gene.VDR encodes the nuclear hormone receptor for vitamin D3 and secondarybile acid lithocholic acid. Mutations in this gene are associated with type II vitamin D-resistant rickets.The PTGS2(prostaglandin-endoperoxide synthase 2)gene is located on chromosome 1andencodes prostaglandin G/H synthase-2, whichcatalyses the first two steps in the metabolism of arachadonic acid. The -765G > C promoter SNP (rs20417) is the best-studied variant in PTGS2.NR1I2 is a key regulator for the expression of genes involved in all stages of drug metabolism and transport. Phase I drugmetabolizing enzymes regulated by PXR/NR1I2 include several CYPs, carboxylesterases, and dehydrogenases. Haplotype analyses also showed differences among the ethnic minoritiesin China and the four Hap Map populations. Conclusion: Our data complement the pharmacogenomics information of ethnic minorities in China provided by the existing database worldwide, and provide a template for the study of pharmacogenomics in various ethnic minority groups in China. These information would provide a theoretical basis for safer drug administration and individualized treatment plans for the ethnic minorities in China.
General Genetics Ltd, Kazakhstan
Title: Pharmacogenetic kit for individual correction of Warfarin and Clopidogrel dosage in central Asian population
Time : 12:00-12:20
Pavel Tarlykov has received his M.Sc. in Biochemistry from Montana State University (Bozeman) in 2009. He is a research scientist at General Genetics Ltd, a startup company involved in pharmacogenetic research, and senior research scientist at the National Center for Biotechnology of the Republic of Kazakhstan. His work is published in many reputed journals.
ADME of drugs significantly depends on individual genetic differences and affects efficacy of drug therapy. Information on the patient’s pharmacogenetic status minimizes occurrence of side effects and complications after the appointment of drugs. It is well established that every population has its own unique set of allelic variants in the genes involved in drug metabolism. One of our goals was to study Kazakh population and its allele frequencies of 158 SNPs that determine susceptibility to major classes of drugs. A total of 320 blood samples were collected from adult individuals of Kazakh origin. Ethical approval was received from the Ethics Committee of the National Center for Biotechnology. Comparative analysis of allele frequencies has revealed that Kazakh population has common genetic characteristics of the neighboring Caucasian and Asian populations. The latest report of Ministry of Health of the Republic of Kazakhstan states that Warfarin and Clopidogrel are major causes of severe side effects in patients with cardiovascular disease. The acquired genotyping data was used to develop a diagnostic kit that is aimed to correct individual dosage of these drugs. The kit includes 8 SNPs representing 5 genes (CYP2C9 (CYP2C9*2, CYP2C9*3), VKORC1 (1173 C>T, 1542 G>С), СYP4F2 (G23454A), CYP2D6 (CYP2D6*3, CYP2D6*4) and CYP1A2*1F (C163A). Real-Time PCR with TaqMan probes was selected and optimized as a genotyping method for diagnostics. Introduction of the in vitro pharmacogenetic diagnostic will result in reduced incidence of adverse reactions and help clinicians to determine therapeutic strategy and treatment dose for Warfarin and Clopidogrel in Central Asian region.