Day 1 :
Keynote Forum
Andreas Scherer
Golden Helix Inc., USA
Keynote: Key success factors implementing precision medicine
Time : 10:00-10:45
Biography:
Andreas Scherer is the CEO of Golden Helix. He is also Managing Partner of Salto Partners, a management consulting firm headquartered in the DC metro area. He has extensive experience in managing growth as well as orchestrating complex turn-around situations. He holds a PhD in Computer Science from University of Hagen, Germany and a Master of Computer Science from University of Dortmund, Germany. He is author and co-author of over 20 international publications and has written books on project management, the internet and artificial intelligence. His latest book, “Be Fast or Be Gone”, is a prize winner in the 2012 Eric Hoffer Book Awards competition and has been named as finalist in the 2012 Next Generation India Book Awards.
Abstract:
Almost 2500 years ago, Hippocrates captured one of the key principles underlying precision medicine. In the 21st century we take the understanding of the individual characteristics of a person to a new level. By leveraging information about an individual’s genome we are able to increase the effectiveness of medical treatments. The goal is to have more successful outcomes by providing targeted therapies. The cost of sequencing a genome has dramatically dropped since the first draft of the human genome sequence was published in 2001. This is a key enabler. Now, it is very much in reach for a wide range of patients to receive a gene panel analysis or even a whole exome/genome analysis. But there is more that is required. Through a collaborative effort between clinicians, pharma companies, scientists and regulatory agencies we are working on a new framework for standard care on a global basis. This talk will discuss the components that will facilitate the power of precision medicine. Now, the concept of Precision Medicine is not new. Medical practice has always been about treating each individual patient. Clinicians are very familiar with the fact that different patients respond differently to specific treatments. What is new is that the advances in the field of genomics offer a new ways to develop targeted therapies, diagnose patients and predict who will respond favorably from those targeted therapies. Since the approval of Kalydeco (ivacaftor) on January 31, 2012 by the FDA to help cystic fibrosis patients with G551D mutation, the FDA has approved a number of so called targeted therapies primarily in the cancer space: crizotinib, vemaurafinib, dabrafenib and treminib – each have been approved for use in patients with a particular tumor profile. Precision Medicine is well on its way. This generation experiences a paradigm shift in medicine. Clinicians, empowered by state of the art bioinformatics pipelines can make better informed and more targeted decisions. Patients benefit from individualized treatment plans and better clinical outcomes. There is still a lot to do.
Keynote Forum
Hans Lehrach
Max Planck Institute for Molecular Genetics, Germany
Keynote: Virtualized drug development for (truly) personalized drug therapy
Time : 10:45-11:30
Biography:
Hans Lehrach has obtained his PhD at the Max Planck Institute for Experimental Medicine and the MPI for Biophysical Chemistry in 1974. He has then moved on to Harvard University, Boston (1974-1978) and became Group Leader at EMBL, Heidelberg (1978-1987). He then moved to the Imperial Cancer Research Fund, London (1987-1994) to become Head of the Genome Analysis Department. In 1994 he has returned to Germany to become Director at the MPI for Molecular Genetics (1994-2014). He has founded several biotechnology companies such as Sequana Therapeutics, GPC Biotech, Scienion, Prot@gen, PSF Biotech and Atlas Biolabs. He is the Founder of the Berlin-based company Alacris Theranostics GmbH, specializing in the development of new approaches for personalized medicine for cancer patient diagnosis, treatment and drug stratification. In 2010 he founded the non-for-profit research institute Dahlem Centre for Genome Research and Medical Systems Biology.
Abstract:
Every patient is different. In particular, every tumor is different. Even subgroups of tumor cells can react differently to specific therapies, due to the heterogeneity of many tumors. Drug therapies therefore typically only help a fraction of patients; many patients do not respond with some suffering sometimes severe side effects of ineffective treatments. The ability to identify effects and possible side effects of different drugs on individual patients will, in our view, require highly detailed molecular analyses of every individual patient and his/her individual disease; data that is integral to generating individualized computer models, which can then be used to test the effects of drugs (or other therapies) on the individual. This will, on one hand, provide a basis for a truly personalized selection of therapies optimal for the individual patient, first in cancer patients but increasingly also in other areas of medicine and prevention. It will, however, also open the way to an increasing virtualization of the drug development process, by e.g., virtual clinical trials of drug candidates carried out throughout the development process.
- Pharmacogenomics & Personalized Medicine
Session Introduction
Joe Vockley
Inova Translational MedicineInstitute, USA.
Title: Making genomic medicine a reality in the community hospital setting.
Biography:
Joe Vockley completed his PhD in genetics at The University of Delaware and a post doctoral fellowship and clinical genetics residency at the University of California at Los Angeles (UCLA). He is SVP, CSO and COO of the Inova Translational Medicine Institue and Professor of Pediatrics at the Virginia Commonwealth University, School of Medicine. Dr. Vockley was a Senior Scientists in the pharmaceutical industry, worked his way up to Vice President of Genomics in the biotechnology sector and directed The Cancer Genome Atlas project at the NCI. He has published in the fields of genetics, genomics molecular diagnostics and bioinformatics.
Abstract:
The Inova Translational Medicine Institute (ITMI) is a not-for-profit research institute that spent the past four years enrolling, consenting and banking samples (Blood, Saliva, Urine, Placenta) from families who gave birth at the Inova Fairfax Medical Center (IFMC). To date, over 3500 mother/father/baby family trios have enrolled in two major studies: A preterm Birth Study and an 18 year long childhood longitudinal study. Whole genome sequencing data has been generated on approximately 7000 individuals. Expression, methylation and miRNA data have been generated on the mother’s samples. We have utilized these data to generate novel ancestral genomic references to: 1) Enhance the identification of rare disease-causing variants in WGS data; 2) Perform an in silico newborn screen that is compared to results returned by the Commonwealth of Virginia; 3) Parse cancer-causing genes by ancestry; 4) Generate prediction models for preterm birth; 5) Develop a private hybrid cloud database infrastructure and tools to support research and 6) Launch a pharmacogenomics panel test that is offered free to any baby born at our hospital. ITMI has developed a novel WGS-based test, referred to as a ‘genomic physical’ that evaluates approximately 3000 pediatric and adult onset disease-causing genes as well as inherited familial cancer genes in a clinical laboratory environment to provide patients with an accurate assessment for the risk of developing genetic disease and a clinical interpretation of the WGS results. In combination, these projects and tests are helping the IFMC to integrate genomics into the healthcare of patients in the community hospital.
Amber Dahlin
University of California San Francisco, usa
Title: Large-scale genome-wide association study of asthma.
Biography:
Amber Dahlin, Ph.D., MMSc., is an Instructor of Medicine and an Associate Epidemiologist at Harvard Medical School and Brigham and Women’s Hospital. She received her Ph.D. from the University of Washington, and completed her postdoctoral training at University of California San Francisco and Harvard Medical School, where she also obtained an MMSc. in bioinformatics. Her research is focused on genomics, pharmacogenomics and systems biology approaches in asthma.
Abstract:
Asthma, a genetically heterogeneous disease, affects over 300 million persons globally, and susceptibility to asthma is influenced by environmental and genetic risk factors. Identifying the genetic variants associated with asthma through well-powered genome wide association studies (GWAS) in large populations is needed to elucidate the genetic basis of asthma. We conducted a GWAS in 16,272 patients with asthma and 38,269 unaffected controls from the Kaiser Permanente Northern California’s (KPNC) Genetic Epidemiology Research on Adult Health and Aging (GERA), one of the largest real-life asthmatic populations. Genomic DNA was extracted from saliva samples and used to generate over 675,000 genetic markers by Affymetrix Axiom arrays, and genotypes for six million common variants were imputed using the1000 Genomes Project as the reference. The mean age of the population was 60.6 years and 63.5% were female. We identified 15 genes associated with asthma at a genome-wide significance level of 5x10-08 that were discovered in prior GWA studies, including IL33, IL1RL1, WDR36, TSLP, HLA-DQ1, HLA-DQB1, HLA-DRB1, HLA-DRB4, ORMDL3, ZPBP2, GSDMB, MICB, SMAD3, IKZF3, and LRRC3C. In addition, we also identified eight novel significant associations: PTPRC, HLA-DRB3, HLA-DRB5, HLA-DRB6, PORS1C3, LOC105371988, SNU13 and MEI1. The strongest associations were found in a region of chromosome 6 containing the HLA-DQA1 locus (6p21.3). The top-ranked GWAS SNP, rs9272513, [P=2.2x10-15; OR =0.89] present within an intron of HLA-DQA1, was not previously reported as associated with asthma. Among the top ten SNPs in this region, a second SNP, rs1047989 [OR = 0.90; P = 1.3x10-13] encoded a leucine to methionine substitution at amino acid position 8 of HLA-DQA1, and was also in moderate linkage disequilibrium (r2=0.6) with rs9272513. Replication of these results is ongoing.
Farhad Kamali
Newcastle upon Tyne, United Kingdom.
Title: Effect of genetic, patient and clinical factors on statin-related myotoxicity
Biography:
Farhad Kamali is Professor of Human & Experimental Pharmacology at the Institute of Cellular Medicine, Newcastle University, United Kingdom. He has published well over one hundred articles in peer reviewed journals as well as book chapters. Professor Kamali serves on the editorial board of a number of journals in the areas of clinical pharmacology, pharmacogenetics and haematology. Prof Kamali’s research focuses on the elucidation of the mechanisms of drug-induced toxicity and in particular identifying the risk factors associated with poor outcomes in anticoagulation treatment of thromboembolic disease.
Abstract:
Although statins are generally well-tolerated, statin associated musculoskeletal symptoms (SAMS) are relatively common. True statin-related myotoxicity (SRM) is much less common and rhabdomyolysis, the severest consequence of myopathy, is a rare event. Genetic factors associated with enhanced statin systemic exposure and muscular availability increase the risk of severe myopathy; however it is not clear whether the same or different genetic factors operate across the spectrum of SRM from myalgia to milder myopathy, as encountered in routine practice. The current study examined associations between clinical and genetic factors and SRM in a case-control design study in patients at high cardiovascular risk. 120 SRM cases (who discontinued statins due to intolerable statin related muscle symptoms) and 481 statin tolerant controls (treated with either 40 mg simvastatin or 80 mg atorvastatin daily) were studied. The association between 12 single nucleotide polymorphisms (SNPs) in nine candidate genes [i.e., SLCO1B1, ABCC2, ABCG2, CYP3A4, COQ2, glycine amidinotransferase (GATM), glutathione peroxidases 1 and 4 (GPX1 and GPX4), SLC16A1, SLC16A3] and patient factors (age, sex, BMI, comorbidities and concurrent therapy) with SRM was evaluated. Of the 12 SNPs genotyped, only rs4149056 in SLCO1B1 was associated with SRM (P = 0.031, P = 0.014 in univariate and binary logistic regression analysis, respectively) with odds ratio of 1.60 (95 % CI= 1.05-2.45) and this association was influenced by sex (P= 0.006). In multivariate logistic regression analyses of data only SLCO1B1 rs4149056 genotype (OR=1.72, 95% CI: 1.15- 2.59, P=0.014) and sex (OR=1.72, 95% CI =1.15 - 2.59, P=0.006) were independently associated with SRM. We conclude that genetic factors associated with statin systemic exposure are implicated in the full spectrum of SRM. However among the genetic variants studied here, only SLCO1B1 rs4149056 warrants further evaluation for the identification of patients who may be susceptible to myopathy.
Yuri E. Dubrova
University of Leicester,UK
Title: A Genome-wide Analysis of Mutation Induction in the Mouse Germline
Biography:
Yuri Dubrova has completed his PhD at the age of 27 years from NI Vavilov Institute of General Genetics, Moscow. He is a Professor of Genetics at the Department of Genetics, University of Leicester. He has published more than 90 papers in reputed journals and has been serving as an editorial board member of Mutation Research.
Abstract:
The ability to predict the genetic consequences for humans of exposure to ionizing radiation and chemical mutagens has been one of the most important goals of human genetics in the past fifty years. However, despite numerous efforts, little is known about the genetic effects of radiation exposure in humans and the only definitive evidence for germline mutation induction in vivo in mammals comes from mouse studies. Recent advances in genetic technologies have provided new microarray-based and next generation sequencing-based tools for the genome-wide analysis of genetic variation, which have the potential for characterizing germline mutation in humans and mice. Using microarray-based comparative genomic hybridisation and high depth (>22X) whole genome HiSeq sequencing we have recently carried out a matched case control experiment to investigate the effects of ionizing radiation on germline mutation in mice. We found that the frequency of de novo Copy Number Variants (CNVs) and insertion/deletion events indels was significantly elevated in offspring of exposed fathers. We also showed that the spectrum of induced de novo SNVs is strikingly different; with clustered mutations being significantly over-represented in the offspring of irradiated males. Our study highlights the specific classes of radiation-induced DNA lesions that evade repair and result in germline mutation and paves the way for similarly comprehensive characterizations of other germline mutagens.
MarÃa C Ovejero-Benito
Instituto de Investigación Sanitaria la Princesa (IP), Madrid, Spain
Title: Analysis of DNA methylation of psoriasis patients treated with anti-TNF drugs using bioinformatics tools.
Biography:
María C Ovejero-Benito completed her PhD in 2013 from the Universidad Autónoma de Madrid. Since 2004, she has collaborated in cutting edge projects in areas as different as Cancer, Chemistry, Neurodegeneration, Neurogenesis and Epigenetics. She has performed her research in institutions such as Cajal Institute, NYU, Universidad de Valencia, LGC (UK) and the Spanish Research Council. Her scientific results have been recognized by 6 publications in high-impact factor journals and through the presentation of 3 presentations and 6 posters in scientific meetings. Currently she carries out projects in Pharmacogenetics in Dr. Abad lab in Instituto de Investigación Sanitaria la Princesa.
Abstract:
Psoriasis is a chronic, autoimmune and inflammatory skin disorder related to a combination of genetic, environmental and immune factors that affects to 1.3-2.2% of the world population. This strongly disabling disease interferes with patients’ daily life and presents a wide range of comorbidities such as cardiovascular diseases, cancer and depression that can decrease the life expectancy of psoriasis patients. Anti-TNF drugs have been the main biologic drug to treat moderate-to-severe psoriasis so far and its effectiveness can reach 80%. However, the clinical response to the administration of these drugs varies depending on the genetic and the environment of the patient. To understand this phenomenon, analyses of DNA methylation of patients treated with anti-TNF drugs were performed. Blood samples were collected from 72 patients who suffered from moderate-to-severe psoriasis. DNA extracted from these samples was treated with sodium bisulfite, amplified, labeled, hybridized to methylated and unmethylated probes and microarray scanning platform in HiScanSQ Illumina Inc. Human Methylation450 BeadChips technology was used as it allows the simultaneous analysis of 485,000 individual CpGs sites. After analyzing the results with bioinformatic tools such as Genome Studio, Circos and R version 3.1.2, significative differences in the degree of methylation of several CpG islands were found. These islands regulate the expression of genes that have not been involved so far in the pathology of psoriasis. These results are very promising because they help to seed light to the mechanisms involved in this disease and path the way to find new drugs to treat Psoriasis.
Julie Earl
University Hospital Ramón y Cajal, Spain.
Title: The liquid biopsy: The detection of circulating tumor cells and tumor DNA as prognostic biomarkers in patients diagnosed solid tumors.
Biography:
Julie Earl completed her PhD at the age of 28 years from the University of Liverpool, UK and her postdoctoral studies at the University of Liverpool and the Spanish Cancer Research Center (CNIO) in Madrid, Spain. She is a senior research scientist in the medical oncology department of the university hospital Ramón y Cajal, Madrid, Spain and specializes in cancer genetics and tumor biomarkers, particularly in digestive cancers. She has published more than 20 papers in reputed journals and is also currently the head of the HNPCC clinical diagnostics laboratory and BEAMing technology facility at the hospital.
Abstract:
Although overall cancer survival rates are improving, many patients present with advanced disease with distant metastasis which impacts severely on their survival hopes. The crucial factor to improve prognosis is early detection at a potentially curative stage and adequate management of patients after diagnosis. However, there are few sensitive and specific biomarkers in the clinic that aid the management of these patients. The concept of the liquid biopsy and the detection of Circulating Tumor Cells (CTC) and circulating free tumor DNA (cftDNA) in blood have gained momentum over the last few years. In fact, they have been shown to be potential early indicators of tumor spread that may not be visible on imaging as invasive but localized tumors may shed CTC and DNA into the blood stream before a metastasis is established. However, it is important to be able to distinguish between non-tumor and tumor cells and DNA in these types of studies. Thus we take advantage of the genetic aberrations commonly found in primary tumors that serve as positive indicators of tumor cells and their DNA such as mutant KRAS, EGFR and TP53. The advent of digital PCR allows us to detect minute amounts of DNA in blood that originates from the tumor and has revolutionised these types of biomarker studies. The liquid biopsy samples are of great importance in cancer genomic research, particularly when tissue biopsies specimens are limited and in the future could revolutionise the field of oncology and become an invaluable diagnostic, prognostic and predicative marker in the field of oncology.
Günter Müller
Institute for Diabetes and Obesity, Germany
Title: Serum Signatures of Low Bias Are Correlated with (Pre-)Diabetic States in Rats
Biography:
Günter Müller has completed his PhD in Genetics at the Ludwig-Maximilians-University (LMU) Munich. After postdoctoral studies at the Universities of Ulm and Heidelberg and habilitation at the LMU he was engaged in drug discovery for type II diabetes at pharmaceutical companies Hoechst AG, Aventis and Sanofi at Frankfurt/Germany for more than 20 years. Currently, he is group leader for biomarker research at the Helmholtz Center Munich. He has published more than 150 original papers, reviews, book chapters and patents.
Abstract:
Most conventional approaches toward biomarker identification have failed to provide tools that would enable to stratify cellular stress responses and pave the way for a more personalized medicine for stress-related diseases, such as type 2 diabetes (T2D). We are therefore taking an entirely different path relying on novel technology and a minimal (biophysical) bias. We established and validated a chip-based biosensor based on the principle of surface acoustic waves (SAW) which enables characterization and quantification of extracellular complexes in plasma. These harbor glycosylphosphatidylinositol-anchored proteins (GPI-APs) and phospholipids (ECGAPP). ECGAPP have already been shown to be released from the surface of metabolically relevant cells through non-classical secretory mechanisms in response to metabolic stress as is prevalent during T2D. Importantly, ECGAPP are assumed to differ in level, morphology, structure and biophysical properties between distinct states of (metabolic) stress. Strikingly, GPI-APs have been shown to exhibit high susceptibility for release in ECGAPP from the surface of mammalian cells in response to T2D. The presence of ECGAPP in body fluids of stressed people has not been studied so far, possibly due to conceptual (reductionistic and causal thinking) and technological limitations. To overcome these hurdles, the SAW biosensor will be used for the specific detection and biophysical characterization of ECGAPP. Any specific interaction of ECGAPP with the gold surface via the capturing molecule alpha-toxin and the monitoring molecule annexin-V (for the detection of phospholipids) will result in corresponding changes in the shape of the SAW, altering both their phase and amplitude and thereby reflecting changes in mass loading and biophysical properties. The data indicate that the time-resolved signatures recorded in course of successive binding and releasing of ECGAPP to the chip surface in the presence of differential concentrations of synthetic phosphoinositolglycans (PIG), that interfere with the specific interaction of the core glycan portion of the GPI anchors contained in the ECGAPP and alpha-toxin, differ significantly between sera from wildtype and ZF (either normal or obese) rats with regard to amplitude reductions and between wildtype and ZDF (either normal and obese) rats with regard to phase shifts. Trends in either amplitude reductions or phase shifts were measured between sera from normal and obese ZF rats, normal and obese ZDF obese rats, normal and obese wildtype rats as well as betwee normal ZF and ZDF rats. Measurement of phase shifts and amplitude reductions of SAW exposed to complexes, which interact with the biosensor chip surface via GPI-APs and phospholipids as their constituents as a minimal bias, was sufficient to differentiate between sera from normal and (pre-)diabetic rats on the basis of mass reflecting differences in the amount of ECGAPP released and their putative post-translational modifications as well as on the basis of viscoelasticity reflecting alterations in the spatial configuration and conformation of the ECGAPP constituents. The requirement for the presence of limiting concentrations of PIG, that compete for the interaction of the ECGAPP with the chip, indicate that a subset of ECGAPP is relevant for the successful differentiation, only, rather than that the differentiating signatures represent a summation signal over all ECGAPP released. This phenomenological approach may open new avenues for biomarker research for and the prediction of common diseases since it does not depend on knowledge of the underlying molecular basis for the monitored differences in the ECGAPP signatures a priori as is the case for conventional reductionistic and causal approaches.
Giridharan Periyasamy
Genome Institute of Singapore, Singapore
Title: "Patient Derived Micro Tumor systems: Future Trends Towards Improved Testing Systems - Realizing the Potential of HTS/HCS towards precision medicine..."
Biography:
Dr.Giridharan studied in Centre for Biotechnology at Anna University, India where he obtained his Ph.D. in Biotechnology He is the Head of Centre for High Throughput Phenomics (CHiP-GIS) at the Genome institute of Singapore. His research focus is on the Cancer biology, Drug resistance and signaling pathway networks of human diseases. Prior to his current position, he worked as a Scientific Director of HTS/HCS Screening Core Facility at C-CAMP, NCBS, India and a Group Leader at Piramal Life Sciences Ltd in Mumbai India. He has more than 15 significant publications and 8 patents to his credit.
Abstract:
With increasing breadth and depth of genomics studies across a range of cancers, it is now apparent that there exists significant inter and intra tumoural heterogeneity, with complex genotypes comprising of multiple co-existing genetic and epigenetic alterations. Current efforts at genomic characterization of individual cancers however, has several limitations: A significant proportion of patients invariably develop resistance to current targeted therapies, for which the mechanisms are not fully unraveled, and there remain a lack of treatment options. In this project, we plan to propagate patient derived cell lines in order to allow functional studies that may expand therapeutic opportunities beyond genomic-based markers. Functional studies comprise both chemical and genetic tools that perturb the signaling networks in the primary cell cultures, in order to unravel complex signaling networks that interact through crosstalk and feedback loops, which modify therapeutic vulnerability. Such screens can therefore provide insights into mediators of resistance and sensitivities, yielding predictive biomarkers as well as novel drug combinations to circumvent drug resistance. Two crucial components include an efficient scalable system to explore therapeutic combinations and the development of representative preclinical models: Patient-derived cells in 3D culture models reflect an integration of genetic, epigenetic, and environmental influences, and may closely mimic the chemotherapeutic (or pathway specific inhibitor)-response of the actual tumor in patients. Thus we aim to exploit the relevance and scalability of patient-derived cell lines to perform HTS/HCS based screens.
Ahmed Abdelfatah
National Research Centre, Egypt
Title: Trigonelline attenuates hepatic complications and molecular alterations in high fat high fructose-induced insulin resistance in rats
Biography:
I am aresearch assistant at pharmacology department , National Research Centre. I am a PHD student at faculty of veterinary medicine , cairo university . last yrear i took afullbright prize for the ecxellent innovative idea in aceremony at national research centre. Workoing nowdays at national project on diabetes mellitus in egypt.
Abstract:
The present study aimed to evaluate the effect of trigonelline (TRG) on the hepatic complications associated with high fat high fructose (HFHF)-induced insulin resistance (IR) in rats. IR was induced by adding saturated fat diet and 10% fructose in the drinking water to rats for 8 weeks. Insulin resistant rats were orally treated with TRIG (50 and 100 mg/kg), sitagliptin (SITA; 10 mg/kg) and the combination TRIG (50 mg/kg) with SITA (10 mg/kg) for 14 consecutive days. Afterwards, blood samples were withdrawn from fasting rats; liver and pancreas tissues were isolated. Sera were separated for determination of serum levels of glucose and insulin; to calculate the homeostatic model assessment-IR (HOMA-IR); and for determination of serum liver function. Liver homogenates were used for assessment of hepatic lipids, oxidative stress biomarkers and inflammatory cytokines. Histopathological and DNA cytometery examinations were carried out for hepatic and pancreatic tissues. Moreover, hepatic tissues were examined using Fourier Transform Infrared (FTIR) spectroscopy technique for assessment of any molecular changes. Results of the present study revealed that oral treatment of insulin resistant rats with TRG and its combination with SIT significantly decreased HOMA-IR, hepatic lipids, oxidative stress biomarkers; measured as malondialdehyde and reduced glutathione and the inflammatory cytokine; α-tumor necrosis factor. TRIG and its combination with SITA succeeded to ameliorate the histopathological, DNA cytometery and molecular alteration induced by HFHF. Finally, it can be concluded that TRIG has beneficial effects on the hepatic complications associated with HFHF-induced insulin resistance in rats due to its hypoglycemic effect and antioxidant potential.
Alex Lucas Hanusch
Universidade Federal de Goiás, Brazil
Title: Genotoxicity and Cytotoxicity Evaluation of the Neolignan Analogue 2-(4-Nitrophenoxy)-1-Phenylethanone and its Protective Effect Against DNA Damage
Biography:
Alex Lucas Hanusch has completed his MSc. at the age of 25 years from Universidade federal de Goiás (UFG), Brazil. He is a Cytopatologist of Hospital das Clínicas – UFG - Goiânia, Goiás, Brazil. He has published three papers and 45 abstracts.
Abstract:
Neolignans are secondary metabolites found in various groups of Angiosperms. They belong to a class of natural compounds with great diversity of chemical structures and pharmacological activities. These compounds are formed by linking two phenylpropanoid units. Several compounds that have ability to prevent genetic damage have been isolated from plants, and can be used to prevent or delay the development of tumor cells. Genetic toxicology evaluation is widely used in risk assessment of new drugs in preclinical screening tests. In this study, we evaluated the genotoxicity and cytotoxicity of the neolignan analogue 2-(4- nitrophenoxy)-1-phenylethanone (4NF) and its protective effect against DNA damage using the mouse bone marrow micronucleus test and the comet assay in mouse peripheral blood. Our results showed that this neolignan analogue had no genotoxic activity and was able to reduce induced damage both in mouse bone marrow and peripheral blood. Although the neolignan analogue 4NF was cytotoxic, it reduced cyclophosphamide-induced cytotoxicity. In conclusion, it showed no genotoxic action, but exhibited cytotoxic, antigenotoxic, and anticytotoxic activities.
Lifshits G.I.
ICBFM SB RAS, RUSSIA
Title: New device for home measurement of blood coagulation parameter
Biography:
M.D. Lifshits Galina Israilevna, is the Head of the Laboratory of Personalized Medicine ICBFM SB RAS, professor Novosibirsk State University. He has published more than 100 papers in reputed journals and has been serving as an editorial board member of repute.
Abstract:
Antithrombotic therapy is widely used to prevent thrombotic events. There are inter-individual differences of therapeutic effects and adverse drug reactions (such as bleeding or thrombosis due to the failure of the drug) observed in some patients. The efficacy and safety of antithrombotic drugs is enhanced by the timely control laboratory markers of hemostasis. The problem of antithrombotic therapy is an individual response to drugs depending on genetic factors (CYP2C9, CYP3A4, CYP2C19, and others), metabolic status, food, combination with other drugs. Therefore, individually calibrated doses of drugs should be prescribed based on its effectiveness to qualify for the "safe passage" between the risk of bleeding and the risk of thrombosis, which in both cases may lead to death or disability. These conditions led to the investigation aimed at developing a new device for multiparametric study of blood coagulation and platelet aggregation that allows patients to perform measurements at home using capillary blood. Thus the proposed equipment combines the functionality of two devices: to determine the international normalized ratio (INR) and platelet aggregation in response to ADP, and further to be able to transmit information to the physician using the Internet, as well as it should be portable and easy to use. Now we are testing the device in comparison with standard laboratory methods for measuring INR and platelet aggregation. In addition to the device, we have also developed instructions for personification of multiplicity and conditions of its use by patients depending on the individual genotype.
Chi-Tai Yeh
Taipei Medical University-Shuang Ho Hospital, Taiwan
Title: JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells
Biography:
Chi-Tai Yeh received his Ph.D. in Food Science and Biotechnology from National Chung Hsing University. Dr. Yeh is currently the Research Fellow and Executive Secretary of Department of Research of Taipei Medical University-Shuang Ho Hospital. Dr. Yeh has contributed 2 book chapters, published 35 articles in the field of cancer & nutritional chemistry journal, and got 2 patents in the medical compound of cancer therapy. His major research interests include in cancer cell biology, cancer stem cell research, nutrigenomis and cancer chemoprevention with dietary phytochemicals.
Abstract:
Neuroblastoma (NB) is a common neural crest-derived extracranial solid cancer in children. Among all childhood cancers, NB causes devastating loss of young lives as it accounts for 15% of childhood cancer mortality. Neuroblastoma, especially high-risk stage 4 NB with MYCN amplification has limited treatment options and associated with poor prognosis. This necessitates the need for novel effective therapeutic strategy. JARID1B, also known as KDM5B, is a histone lysine demethylase, identified as an oncogene in many cancer types. Clinical data obtained from freely-accessible databases show a negative correlation between JARID1B expression and survival rates. Here, we demonstrated for the first time the role of JARID1B in the enhancement of stem cell-like activities and drug resistance in NB cells. We showed that JARID1B may be overexpressed in either MYCN amplification (SK-N-BE(2)) or MYCN -non-amplified (SK-N-SH and SK-N-FI) cell lines. JARID1B expression was found enriched in tumor spheres of SK-N-BE(2) and SK-N-DZ. Moreover, SK-N-BE(2) spheroids were more resistant to chemotherapeutics as compared to parental cells. In addition, we demonstrated that JARID1B-silenced cells acquired a decreased propensity for tumor invasion and tumorsphere formation, but increased sensitivity to cisplatin treatment. Mechanistically, reduced JARID1B expression led to the downregulation of Notch/Jagged signaling. Collectively, we provided evidence that JARID1B via modulation of stemness-related signaling is a putative novel therapeutic target for treating malignant NB.
Qiong Shi
Shenzhen University, China
Title: High throughput identification of novel conotoxins from cone snails by multi-transcriptomic sequencing
Biography:
Qiong Shi has completed his PhD from China Zhongshan University and postdoctoral studies from Beijing Normal University and Japan Hokkaido University. Before joining BGI in 2011, he worked at USA National Institutes of Health, University of Maryland and OriGene Technologies Inc. He is the dean of BGI Academy of Marine Sciences, VP and Chief Scientist of BGI Fisheries, a genomics professor at University of Chinese Academy of Sciences and Shenzhen University, and the chief of Shenzhen Key Lab of Marine Genomics. He has published over 60 academic papers and 6 monographs, and acquired 12 Chinese patents.
Abstract:
With an estimation of over 500 species, cone snails are classified into Conus, the biggest genus among marine invertebrates. Cone snails apply a complex cocktail of venom components to capture and digest prey. According to variation in diet, cone snails are divided into piscivorous, molluscivorous and vermivorous groups. In the past few years, our lab has successfully performed transcriptomic sequencing of around 10 species. Here, we summarize our recent data about a special species, Chinese tubular cone snail (C. betulinus), which is the dominant conus species inhabiting the South China sea. The transcriptomes of venom ducts and venom bulbs from a variety of specimens of this species were sequenced using both next-generation sequencing and traditional Sanger sequencing technologies, resulting in identification of a total of 215 distinct conopeptides. Among these, 183 were novel conopeptides, including 9 new superfamilies. It appears that most of the identified conopeptides are synthesized in the venom duct, while a handful of conopeptides are identified only in the venom bulb and at very low levels. Variation in conopeptides from different specimens of C. betulinus was observed, which suggested the presence of intraspecific variability in toxin production at the genetic level. These novel conopeptides provide a potentially fertile resource for development of new pharmaceuticals and a pathway for discovery of new conotoxins. Upon acceptance for publication of these results in GigaScience, we initiated construction of the first draft genome of the Chinese tubular cone snail, which is expected to be finished in 2016.
Jie Liu
Central South University, China.
Title: The mechanism of β-blockers on breast cancer proliferation and the influence of ADRB2 polymorphisms on β-blockers’ anti-proliferation
Biography:
Jie Liu, the assistant professor of Department of Clinical Pharmacology, Central South University, has completed her PhD from Central South University and finished postdoctoral studies in Xiangya hospital. From 2014 to 2015, she went to DeBartolo Family Personalized Medicine Institute, Division of Population Sciences, Moffitt Cancer Center, as visiting scholar. She is the assistant of director in Xiangya medical laboratory central and a commission of Chinese society of Pharmacology. She has published more than 20 papers in reputed journals and focused on the influence of genetic variation in drug target such as ADRB1, ADRB2, DRD2 and GR on individual difference.
Abstract:
β-blockers are regular drugs used for cardiovascular diseases. However, increasing studies proposed that β-blockers could be potential anti-cancer drugs, especially for breast cancer, which could significantly improve patients’ survival. β adrenergic receptors are important drug target and polymorphisms in ADRB2 might affect individual-difference. We studied the mechanism of β-blockers in MDA-MB-231 proliferation and focused on four haplotypes comprised by R16G and Q27E of ADRB2 to discover their influence on β-blockers’ anti-proliferation in HEK293. AlarmBlue assay was used to measure cell viability and propranolol and ICI118,551 reduced cell viability by concentration dependently, and have better effect than metoprolol in MDA-MB-231 (p<0.05); flow cytometry assay was used to detect cell cycle distribution and propranolol (200μM) and ICI118,551 (150μM) could cause G1/S phase arrest compared to control(propranolol: G1 54.9±5.3%, S 15.1±2.3%; ICI118,551: G1 61.7±2.9%, S 11.5±6.6%; control: G1 45.8±1.0%, S 23.7±2.4%) (p<0.05); propranolol and ICI118,551 were also observed to lower the expression of p-ERK, p-p38 and COX-2 in MDA-MB-231. Four plasmids were transfected into HEK293. Q-PCR was used to detect mRNA level of ADRB2 and R16Q27 haplotype had higher expression level than others (p<0.05). MTS assay was used to measure cell viability and there is no difference between four haplotypes (p>0.05); further treated with ICI118,551 for 24h, R16Q27 haplotype have lower cell viability (p<0.05) and lower expression of p-ERK and COX-2 (ICI118,551: 80μM). β-blockers inhibited breast cancer cell proliferation might be related to MAPK /COX-2 pathway; R16Q27 haplotype had better drug response, offering genetic guidance for clinic therapy.
Saeed Tarverdizadeh
Tehran University of Medical Sciences, Iran.
Title: Medical Ethics in Genetic Testing
Biography:
Saeed Tarverdizadeh, an enrolled student in Faculty of Medicine, Tehran University of Medical sciences. I have successfully accomplished fifth year and currently in my 6th academic year. I'm currently a member in Students' Scientific Research Center. I have published 3 papers in reputed journals.
Abstract:
Practice standards in medical genetics provide an implied guide to the ethical, legal, and social implications of genetic tests. The public use of nondirective counseling reflects the principle that many testing choices should be determined by personal values. Growing knowledge about the genetics of disease is generating remarkable ethical dilemmas for genetic services, As well as the clinical purposes for genetic testing are increasing. Along with diagnosing disease, some genetic tests can identify inherited susceptibility to future disease, making it possible to modify anticipation and prevention strategies individually. Meanwhile, genetic profiling may also ultimately provide a means to optimize drug treatments. This review will discuss genetic counseling, types of genetic testing and also the importance of genetic services in the health policies. In addition, we mentioned to ethics science in biomedicine and criteria which concern with autonomy informed, decision Informed and consent confidentiality results in genetic services. In continue we explained different aspects of screening, genetics tests and social rights; genetics tests and insurance companies; genetic tests and involvement of other family members; ethical challenges in postnatal diagnosis, prenatal diagnosis, genetic counseling and consanguineous marriage. Eventually, it can be inferred that medical genetics community plays a key role in the management of ethical challenges of genetic services, however multidisciplinary approach is needed. Likewise, cultural, social, economical conditions and religion must be addressed in solving this dilemmas.
Saeed Tarverdizadeh
Tehran University of Medical Sciences, Iran.
Title: Autosomal Recessive Non Syndromic Hearing Loss (ARNSH); Different Mutations Spectrum in Iran
Biography:
Saeed Tarverdizadeh , an enrolled student in Faculty of Medicine, Tehran University of Medical sciences. I have successfully accomplished fifth year and currently in my 6th academic year. I'm currently a member of Students' Scientific Research Center. I have published 3 papers in reputed journals
Abstract:
Sensorineural hearing loss is the most common disorder in humans that heterogeneity is high, and one out of every 1,000 to 2,000 newborns, affecting by mentioned disorder. More than 50 percent of the causes of deafness have been attributed to genetic factors. Non-syndromic hearing loss include more than 70 percent of cases of hereditary deafness; which 85% of NSHL have autosomal recessive hereditary pattern. So far, more than 100 loci for this type of hearing loss are estimated. Nuclear and mitochondrial gene mutations can cause this disease. Of which DFNB1 locus is responsible for half of recessive deafness; including transfer protein genes and ion channel protein like connexin 26 and 30. In Iran, this locus is a primary cause of hearing loss. Which GJB2 mutations especially 35del G play important role in developing hearing loss in Iran. After that, mutations in SLC26A4 gene in DFNB4 locus are the second cause of ARNSH in our country. The next locus to study could be DFNB59 that contains PJVK gene and it's highly prevalent in Iran. Also Mutations in mitochondrial genes such as 12S rRNA genes are involved in development of pre lingual non-syndromic hearing loss.
Saeed Tarverdizadeh
Tehran University of Medical Sciences, Iran.
Title: Pharmacogenetics in Breast Cancer Therapy; Patient’s Genetics Profile in TRASTUZUMAB and TAMOXIFEN Prescription
Biography:
Saeed Tarverdizadeh, an enrolled student in Faculty of Medicine, Tehran University of Medical sciences. I have successfully accomplished fifth year and currently in my 6th academic year. I'm currently a member in Students' Scientific Research Center. I have published 3 papers in reputed journals.
Abstract:
Breast cancer that is caused by the Accumulation of genetic and epigenetic factors, is one of the main causes of death resulted from cancer. Various therapeutic ways have been introduced for this cancer and the traditional diagnosis and treatment is based on the prognosis estimation using cancer anatomic features (TNM system) and clinical results, but studies show the different responses of these treatments and recurrence after those in some patients. This diversity has resulted by the difference in biological and molecular characteristics. So Genomic and molecular studies became more important and the role of targeted treatment based on an individual's genome was highlighted. Today, the progress in personalized medicine using specific individual genome profile has been possible. The ultimate goal of such studies, in the setting of the personalized medicine, is providing markers which can be used to risk assessment of progressing disease. This new science cause great development in the treatment of breast cancer by recognition of specific markers and application of targeted treatment like monoclonal antibodies which Trastuzumab and Tamoxifen are the most common examples. The aim of this review is describing the different aspects of personalized medicine in the breast cancer treatment.
- Genome Medicine| Future trends in Genomics| Biomarkers & Molecular Markers |Bioinformatics in Genomics| Plant Genomics | Pharmacogenomics & Personalized Medicine| Cancer Genomics
Chair
Gerald J Wyckoff
University of Missouri-Kansas City, USA
Co-Chair
Yuri E Dubrova
University of Leicester, UK
Session Introduction
Gerald J Wyckoff
University of Missouri-Kansas City, USA
Title: The next generation of genomicists
Time : 11:45-12:15
Biography:
Gerald J Wyckoff is currently focusing on how evolutionary knowledge can factor into drug discovery. He has been creating and deploying new algorithms for better handling the targets of new chemical entities. His lab deals with aspects of Bioinformatics drug development and study of evolutionary processes at the molecular level.
Abstract:
The past challenges of genomics inform the future issues that will confront the “next generation” of genomicists and we need to examine some of the mistakes of the past to not repeat those mistakes in the future. Clear issues revolve around failing to plan for future disruptive technologies, trying to fix problems of the “last generation” of genomics, inadequate data collection and annotation that will lead to loss of data or unusable data and a failure of collaboration among labs collecting genomics data or setting up biobanks and repositories. These issues are training issues as much as they are scientific ones, so we need to look at how to set up our curriculums to adequately prepare students not just for the jobs they will want immediately but for those careers they want to have in twenty years. Considering how training takes place now, this might mean disrupting our own modes of teaching and relying more on online learning and MOOCs as opposed to the “apprentice-like” system that is generally in place, particularly for MS and PhD students. Exposing those students to the cutting-edge problems being encountered by institutions trying to solve immediate problems will prepare them for encountering new, novel issues across their careers but might draw attention away from focusing on immediate problems that are generally the focus of many MS and PhD theses. We will present a series of potential problems and discuss some potential modes for solving the training and technical issues that they pose.
Yuri E Dubrova
University of Leicester, UK
Title: A genome-wide analysis of mutation induction in the mouse germ-line
Time : 12:15-12:45
Biography:
Yuri E Dubrova has completed his PhD from NI Vavilov Institute of General Genetics, Moscow. He is a Professor of Genetics at the Department of Genetics, University of Leicester. He has published more than 90 papers in reputed journals and has been serving as an Editorial Board Member of Mutation Research.
Abstract:
The ability to predict the genetic consequences for humans of exposure to ionizing radiation and chemical mutagens has been one of the most important goals of human genetics in the past fifty years. However, despite numerous efforts, little is known about the genetic effects of radiation exposure in humans and the only definitive evidence for germ-line mutation induction in vivo in mammals comes from mouse studies. Recent advances in genetic technologies have provided new microarray-based and next generation sequencing-based tools for the genome-wide analysis of genetic variation, which have the potential for characterizing germ-line mutation in humans and mice. Using microarray-based comparative genomic hybridization and high depth (>22X) whole genome HiSeq sequencing we have recently carried out a matched case control experiment to investigate the effects of ionizing radiation on germ-line mutation in mice. We found that the frequency of de novo Copy Number Variants (CNVs) and insertion/deletion events indels was significantly elevated in offspring of exposed fathers. We also showed that the spectrum of induced de novo SNVs is strikingly different; with clustered mutations being significantly over-represented in the offspring of irradiated males. Our study highlights the specific classes of radiation-induced DNA lesions that evade repair and result in germ-line mutation and paves the way for similarly comprehensive characterizations of other germ-line mutagens.
Tamara Raschka
Fraunhofer Institute for Algorithms and Scientific Computing, Germany
Title: Analytical strategy to unravel novel candidates from Alzheimer's disease gene regulatory networks using public transcriptomic studies
Time : 12:45-13:15
Biography:
Tamara Raschka has received her Bachelor's degree from University of Applied Science Koblenz in 2015 and she is currently pursuing Masters in Applied Mathematics, Koblenz. She has joined Fraunhofer SCAI, Department of Bioinformatics as a student in March 2015. Her research work mainly focuses on building robust approaches for analyzing public gene expression studies to explore novel and previously unknown biomarkers in a defined disease context. Currently, she is involved in publicly funded IMI project AETIONOMY where the goal is to build a mechanism based taxonomy aiding in classification of disease sub groups for patient stratification.
Abstract:
Alzheimer's disease (AD) is the most common type of dementia, progressively destroying cognitive capabilities. Despite recent progress, there are no available curable drugs; questioning our current knowledge of AD pathology. Gene regulatory networks (GRNs), generated from meta-analysis of existing studies, could help us revisit our mechanistic understanding. However, they do not elaborate on the context specificity and additionally, miss out on lesser studied genes given the tendency to focus on differential expressed genes and prior knowledge. In this poster, we present a novel strategy to determine common mechanistic patterns across all publicly available AD gene expression datasets. An optimized method of BC3Net and WGCNA were used to get robust and coherent gene regulatory patterns. This approach leverages the power of literature and iterative functional enrichment approach (derived from the data) to define context specificity. The results show significant enrichment for pathways across disparate datasets that are involved in key signaling mechanisms, like neurotrophin and calcium signaling. Interestingly, there are no common genes involved in these pathways across datasets. Among these, genetic variant and linkage disequilibrium analysis prioritized novel candidate genes, which are less studied in AD, but prominent in AD comorbidity. Some of these genes encode for cytokines, which are part of the immune response, responsible for the cell growth and differentiation and inflammation. For the first time we show that functional enrichment to generate GRNs in neurodegeneration reveal unknown yet novel biomarkers. This may lead the way to mitigate the black-box pathogenesis of AD.
Alex Lucas Hanusch
Universidade Federal de Goiás, Brazil
Title: Genotoxicity and cytotoxicity evaluation of the neolignan analogue 2-(4-Nitrophenoxy)-1-phenylethanone and its Protective effect against DNA damage
Time : 14:00-14:30
Biography:
Alex Lucas Hanusch has completed his MSc from Universidade Federal de Goias (UFG), Brazil. He is a Cytopathologist of Hospital das Clinicas, UFG, Brazil. He has published three papers and 45 abstracts to his credit.
Abstract:
Neolignans are secondary metabolites found in various groups of Angiosperms. They belong to a class of natural compounds with great diversity of chemical structures and pharmacological activities. These compounds are formed by linking two phenylpropanoid units. Several compounds that have ability to prevent genetic damage have been isolated from plants and can be used to prevent or delay the development of tumor cells. Genetic toxicology evaluation is widely used in risk assessment of new drugs in preclinical screening tests. In this study, we evaluated the genotoxicity and cytotoxicity of the neolignan analogue 2-(4-nitrophenoxy)-1-phenylethanone (4NF) and its protective effect against DNA damage using the mouse bone marrow micronucleus test and the comet assay in mouse peripheral blood. Our results showed that this neolignan analogue had no genotoxic activity and was able to reduce induced damage both in mouse bone marrow and peripheral blood. Although the neolignan analogue 4NF was cytotoxic, it reduced cyclophosphamide-induced cytotoxicity. In conclusion, it showed no genotoxic action but exhibited cytotoxic, antigenotoxic and anticytotoxic activities.
Agnieszka Zmienko
Poznan University of Technology, Poland
Title: Multiallelic copy number variations of MSH2-AT3G18530-AT3G18535 genes in Arabidopsis thaliana: In-depth analysis of genotypes, mechanisms leading to their formation and the functional implications
Time : 14:30-15:00
Biography:
Agnieszka Zmienko has completed her PhD in 2006. She works as a Research Scientist in the Institute of Bioorganic Chemistry, Polish Academy of Sciences and as an Assistant Professor in the Institute of Computing Science of Poznan University of Technology. She is a team Member of the ECBiG Regional Center which provides facilities, tools and databases for multi-level studies of biological systems. She has focused on plant genomics and transcriptomics and co-authored 15 papers in this field.
Abstract:
Copy number variations (CNVs) are intraspecies duplications/deletions of large DNA segments (>1 kb). Because of the ability to alter the gene structure or copy number CNVs may influence gene expression and by the dosage effect, the interaction of gene products within the protein and metabolic networks. Such alterations may have no phenotypic effect, but often they account for adaptive or maladaptive traits and contribute to genome evolution or phenotypic variation. We adopted two experimental techniques, multiplex ligation-dependent probe amplification and droplet digital PCR to measure the copy number of specific sequences in Arabidopsis thaliana. With those approaches we performed an in-depth analysis of a complex multiallelic CNV encompassing 3 neighboring genes (MSH2, AT3G18530 and AT3G18535). We evaluated the gene copy numbers in a large population of 189 A. thaliana ecotypes and analyzed the CNV breakpoints and the flanking regions. Based on the sequence data and eco-geographical distribution of AT3G18530-AT3G18535 deletion and duplication genotypes we created a model of non-allelic homologous recombination (NAHR) mediated by low copy repeats flanking the two genes. We propose that the observed dupl-2 and del-2 genotypes originate from reciprocal products of interchromatidial/interchromosomal NAHR. Furthermore, we performed gene expression studies to evaluate the possible consequences of CNV on the evolution and functionality of MSH2, AT3G18530 and AT3G18535 genes. In light of those data, the perspectives of utilizing natural CNV phenomenon for functional gene analysis will be discussed.
Giridharan Periyasamy
Genome Institute of Singapore, Singapore
Title: Patient derived micro tumor systems: Future trends towards improved testing systems, Realizing the potential of HTS/HCS towards precision medicine
Time : 15:00-15:30
Biography:
Giridharan Periyasamy studied at Centre for Biotechnology at Anna University, India where he obtained his PhD in Biotechnology. He is the Head of Centre for High Throughput Phenomics (CHiP-GIS) at the Genome Institute of Singapore. His research focus is on the cancer biology, drug resistance and signaling pathway networks of human diseases. Prior to his current position, he has worked as a Scientific Director of HTS/HCS Screening Core Facility at C-CAMP, NCBS, India and a Group Leader at Piramal Life Sciences Ltd., in Mumbai, India. He has more than 15 significant publications and 8 patents to his credit.
Abstract:
With increasing breadth and depth of genomics studies across a range of cancers, it is now apparent that there exists significant inter and intra-tumoral heterogeneity, with complex genotypes comprising of multiple co-existing genetic and epigenetic alterations. Current efforts are at genomic characterization of individual cancers however, has several limitations: A significant proportion of patients invariably develop resistance to current targeted therapies, for which the mechanisms are not fully unraveled and there remain a lack of treatment options. In this project, we plan to propagate patient derived cell lines in order to allow functional studies that may expand therapeutic opportunities beyond genomic-based markers. Functional studies comprise both chemical and genetic tools that perturb the signaling networks in the primary cell cultures, in order to unravel complex signaling networks that interact through crosstalk and feedback loops, which modify therapeutic vulnerability. Such screens can therefore provide insights into mediators of resistance and sensitivities, yielding predictive biomarkers as well as novel drug combinations to circumvent drug resistance. Two crucial components include an efficient scalable system to explore therapeutic combinations and the development of representative preclinical models: Patient-derived cells in 3D culture models reflect an integration of genetic, epigenetic and environmental influences and may closely mimic the chemotherapeutic (or pathway specific inhibitor)-response of the actual tumor in patients. Thus we aim to exploit the relevance and scalability of patient-derived cell lines to perform HTS/HCS based screens.
Ebtesam Al-Ali
Kuwait Institute for Scientific Research, Kuwait
Title: Phylogenetic analysis of TYLCV on tomato plants in Kuwait
Time : 15:45-16:15
Biography:
Ebtesam Al-Ali has obtained her BSc in 1993 from Kuwait University, worked for Kuwait University as Research Assistant, then joined KISR in 1993 and led 5 projects. She has published more than 5 papers in reputed journals and international conferences. Her field of experience, in plant virus detection, primer design, cloning and sequencing, ELISA, DNA Extraction, PCR Amplification, RCA Rolling Circle Amplification, TYLCV detection on tomatoes, also trained twice in the University of Wisconsin Madison under the supervision of Prof. Amy Charkowski as well as at the University of Washington state under supervision of Pro. Hanu Pappu.
Abstract:
Viral diseases of plants are widespread and cause significant economic losses in many crops. A survey of tomato viral diseases in Kuwait was conducted, the high economic losses of tomato crops induced by whitefly emerged a rapid action for identification and molecular characterization of the virus species in order to recommend appropriate control strategies. Tomato Yellow Leaf Curl Virus (TYLCL) was reported as a major pest of tomato. TYLCV isolated from severely diseased tomatoes collected over a two-year period in the main tomato growing area of Kuwait (Abdaly North) was characterized at the molecular level and the complete genomic sequence was determined. Based on the genome structure and organization and phylogenetic analysis, the Begomovirus was found to be a strain of TYLCV. One isolate that was characterized in this study had 97% and 95% nucleotide sequence identity with previously characterized Kuwaiti isolate, TYLCV-KISR and the highest sequence identity (95%) was with that of TYLCV-Almeria (Spain) isolate. Phylogenetic analysis showed that the Kuwait isolate could be a novel variant of TYLCV and suggested to be in a different lineage from known TYLCV sequences.
Martin Falk
DNA repair in head and neck cancers and their radiosensitivity
Title: DNA repair in head and neck cancers and their radiosensitivity
Time : 16:15-16:45
Biography:
Martin Falk is the Head of the Department of Cell Biology and Radiobiology at the Institute of Biophysics, Czech Academy of Sciences, Brno, CR. He has completed his PhD in Molecular Biology and Genetics from Masaryk University Brno, CR, in 2004. He has published over 30 papers with about 500 citations, given 26 invited lectures at international conferences and has been serving as an Editorial Board Member of several reputed journals. In 2009, he has been awarded the Premium of Otto Wichterle devoted by the Czech Academy of Sciences to outstanding young scientists. His research interests include radiobiology and cancer biology.
Abstract:
Head and neck (H & N) tumors are aggressive neoplasms located close to vital tissues. This makes their surgical removal often very risky and mutilating. Non surgical approaches as chemotherapy and radiotherapy are therefore preferable but only about 50% of H & N tumors respond to this conservative treatment. Unfortunately, we still miss a tool allowing for pre therapeutic selection of H & N cancer patients who will benefit from conservative therapy or primary surgery. Blind application of radiotherapy is risky since the rescue surgery (if radiotherapy fails) and consecutive patients' recovery is complicated by radiation damage caused to normal tumor surrounding tissue. Clinicians thus permanently face to a serious 'First-Therapy Dilemma'. The purpose of our work is to better understand the heterogeneity of H &N tumors in terms of their response to different ionizing radiations (gamma rays, protons and accelerated ions), reveal molecular causes of their radiosensitivity/radioresistance and potentially find a biomarker predicting these characteristics. For the first time in this context, we prepared primocultures of several different cell types (normal fibroblasts, tumor associated fibroblasts and tumor cells per se) from patients' tumors, characterized their basic molecular genetics features and compared their survival and DNA double strand break (DSB) capacity after gamma ray and proton irradiation, respectively.
Maria C Ovejero-Benito
Instituto de Investigación Sanitaria la Princesa, Spain
Title: Analysis of DNA methylation of psoriasis patients treated with anti-TNF drugs using bioinformatics tools
Time : 16:45-17:15
Biography:
Maria C Ovejero-Benito has completed her PhD in 2013 from the Universidad Autonoma de Madrid. Since 2004, she is collaborated in cutting edge projects in areas of cancer, chemistry, neurodegeneration, neurogenesis and epigenetics. She has performed research in institutions such as Cajal Institute, NYU, Universidad de Valencia, LGC, UK and the Spanish Research Council. Her scientific results have been recognized by 6 publications in high-impact factor journals and through 3 presentations and 6 posters in scientific meetings. Currently she carries out projects in Pharmacogenetics in Dr. Abad Lab in Instituto de Investigación Sanitaria la Princesa.
Abstract:
Psoriasis is a chronic, autoimmune and inflammatory skin disorder related to a combination of genetic, environmental and immune factors that affects to 1.3-2.2% of the world population. This strongly disabling disease interferes with patients’ daily life and presents a wide range of comorbidities such as cardiovascular diseases, cancer and depression that can decrease the life expectancy of psoriasis patients. Anti-TNF drugs have been the main biologic drug to treat moderate-to-severe psoriasis so far and its effectiveness can reach 80%. However, the clinical response to the administration of these drugs varies depending on the genetic and the environment of the patient. To understand this phenomenon, analyses of DNA methylation of patients treated with anti-TNF drugs were performed. Blood samples were collected from 72 patients who suffered from moderate to severe psoriasis. DNA extracted from these samples was treated with sodium bisulfite, amplified, labeled, hybridized to methylated and unmethylated probes and microarray scanning platform in HiScanSQ Illumina Inc. HumanMethylation450 BeadChips technology was used as it allows the simultaneous analysis of 485,000 individual CpGs sites. After analyzing the results with bioinformatic tools such as Genome Studio, Circos and R version 3.1.2, significative differences in the degree of methylation of several CpG islands were found. These islands regulate the expression of genes that have not been involved so far in the pathology of psoriasis. These results are very promising because they help to seed light to the mechanisms involved in this disease and path the way to find new drugs to treat psoriasis.
Sara Teresinha Olalla Saad
State University of Campinas, Brazil
Title: Screening of genetic variants in familial case of myeloid neoplasm using exome sequencing
Time : 17:15-17:45
Biography:
Sara Teresinha Olalla Saad is a Member of the Editorial Board of the Brazilian Journal of Medical and Biological Research and Referee for the journals: International Archives of Internal Medicine and Clinical and Laboratory Hematology. Her research interests include functional investigation and characterization of the involvement of new target genes and new therapies for the treatment of myelodysplasic syndromes and in leukemic lineages, clinical and molecular investigation of chronic anemias, including hereditary anemias such as sickle cell disease, deficiency of pyruvate kinase and glucose-6-phosphate dehydrogenase, spherocytosis and elliptocytosis, among others.
Abstract:
The introduction of the next-generation sequencing technologies on the research of myeloid neoplasms has provided valuable contributions on the identification of new molecular biomarkers, more accurate risk ratings and more assertive treatments. This study aimed to identify through exome sequencing specific genetic variants in a family with two sisters (39 and 40) with primary myelofibrosis and history of longtime exposure to pesticides DDT-type. To investigate the genetic variants in these patients, we proceeded to the whole-exome sequencing of DNA samples from bone marrow CD34+ hematopoietic stem cells and germline cells from peripheral blood (CD3+ lymphocytes). The samples were sequenced on HiSeq 2500 (Illumina, Inc.), strict mode and the bioinformatics analysis was conducted with the following tools, respectively: NGSQC Toolkit, BWA-backtrack, SAM tools, GATK and ANNOVAR. A set of 110 genes implicated on the pathogenesis of myeloid neoplasms has been selected for the variants filtering. The variants were considered as possibly associated to these neoplasms when they have fulfilled these criteria: Located in exonic regions, coverage values ≥30X and global minor allele frequency <1%, predicted as deleterious by SIFT software and predicted as pathogenic by PolyPhen2 tool. The filtering has identified the GATA1 Thr263Met in the bone marrow (BM) and peripheral blood (PB) of both patients and the JAK3 Val718Leu in the BM of the younger sister. The change in GATA1 is located at highly conserved region of the protein and contains no record in databases of variants to date. Besides, three variants in genes encoding drug-metabolizing enzymes were identified in one or another patient: CYP3A5 Gly31fs, CYP2A6 Ser467Stop and CYP2B6 Thr67Met.
- Micro RNA| Clinical Genomics| mRNA Analysis | Next Generation Sequencing | Comparative Genomics| Genome Engineering | Functional Genomics | Microbial Genomics
Location: Golden Tulip Berlin - Hotel Hamburg
Chair
Janos Zempleni
University of Nebraska-Lincoln, USA
Co-Chair
Martin Falk
Czech Academy of Sciences, Czech Republic
Session Introduction
Janos Zempleni
University of Nebraska-Lincoln, USA
Title: Delivery of functional RNA cargos by dietary exosomes from cow’s milk in C57BL/6J mice
Time : 9:45-10:15
Biography:
Janos Zempleni has obtained his PhD in Nutrition Science from the University of Giessen, Germany and received Postdoctoral training at Innsbruck University Medical School, Austria, Emory University School of Medicine, USA and the University of Arkansas for Medical Sciences, USA. He is the Willa Cather Professor of Molecular Nutrition at the University of Nebraska-Lincoln, USA, where he directs an NIH-funded obesity prevention and nutrient signaling center. He has published more than 200 papers and has been continuously funded by federal agencies and foundations for 15 years and is a Fellow of the American Association for the Advancement of Sciences.
Abstract:
Various species of RNA, including microRNAs and mRNAs are encapsulated in exosomes from dietary sources, including cow’s milk. Encapsulation confers protection against degradation and provides a vehicle for intestinal uptake of exosomes and their RNA cargos by endocytosis. In previous studies we challenged the paradigm that microRNAs and mRNAs are derived solely from endogenous sources. We demonstrated that milk consumption causes a postprandial increase in plasma microRNAs (including bovine-specific microRNAs), endogenous microRNA synthesis is insufficient to compensate for dietary microRNA depletion and dietary microRNA are delivered to circulating cells and tissues to regulate gene expression in host organisms. Here we assessed the bioavailability and distribution of milk exosomes endogenously and exogenously labeled with fluorophores, phenotypes of exosome depletion and the functionality of milk exosome cargos in wild-type and transgenic mice. Dose-response studies of milk exosomes were conducted using a live mouse imaging system. Our data suggest that mice absorb milk exosomes and that a fraction of these exosomes escapes re-packaging in the intestinal mucosa and reaches tissues in intact form; the majority of exosomes accumulates in macrophages. Exosome feeding studies suggest that dietary depletion elicits a substantial decrease in fertility, intrauterine growth and postnatal survival; Exosome depletion also caused aberrant purine metabolism. Ongoing studies suggest that dietary exosomes extend the life span of tamoxifen-inducible Drosha conditional knockout mice and that mRNA cargo in milk exosomes can be translated into proteins.
Maria C Ovejero-Benito
Instituto de Investigación Sanitaria la Princesa, Spain
Title: Polymorphisms that regulate the response to Etanercept in psoriatic patients
Time : 10:15-10:45
Biography:
Maria Carmen Ovejero-Benito has completed her PhD in 2013 from the Universidad Autonoma de Madrid. Since 2004, she is collaborated in cutting edge projects in areas of cancer, chemistry, neurodegeneration, neurogenesis and epigenetics. She has performed research in institutions such as Cajal Institute, NYU, Universidad de Valencia, LGC, UK and the Spanish Research Council. Her scientific results have been recognized by 6 publications in high-impact factor journals and through 3 presentations and 6 posters in scientific meetings. Currently she carries out projects in Pharmacogenetics in Dr. Abad Lab in Instituto de Investigación Sanitaria la Princesa.
Abstract:
Etanercept is an anti-TNF biologic drug effective for moderate-to-severe psoriasis. However, 30% of the patients do not respond to this drug. In this study, the association between 121 polymorphisms with the response to etanercept was evaluated in patients with moderate-to-severe plaque psoriasis. The results of the multivariate analysis showed an association between polymorphisms rs13437088 (HLAB/MICA), rs96844 (MAP3K1), rs2431697 (PTTG1), rs9304742 (ZNF816A) and the response to etanercept treatment. PASI75 at 3 months of treatment with this drug was used as an efficacy measure. The association between the polymorphisms in the MAP3K1 and ZNF816A genes and the response to anti-TNF drugs with the PASI75 at 3 months was validated in a previous study from our lab. This is the first study to show an association between these polymorphisms and the specific response to etanercept treatment in psoriasis patients. However, these biomarkers should be validated in large-scale studies before implementation in clinical practice.
Ebtesam Al-Ali
Kuwait Institute for Scientific Research, Kuwait
Title: Molecular characterizing of TYLCV in cucumber plants in Kuwait
Time : 10:45-11:15
Biography:
Ebtesam Al-Ali has obtained her BSc in 1993 from Kuwait University and worked for Kuwait University as Research Assistant, then joined KISR in 1993 and led 5 projects. She has published more than 5 papers in reputed journals and international conferences. Her field of experience is in plant virus detection, primer design, cloning and sequencing, ELISA, DNA extraction, PCR amplification, RCA-Rolling Circle Amplification, TYLCV detection on tomatoes, also trained twice in the University of Wisconsin Madison under the supervision of Professor Amy Charkowski as well as University of Washington state under supervision of Professor Hanu Pappu.
Abstract:
High scores of vegetable crop losses had been recorded in Kuwait agricultural farms, viral diseases were the main causal agent of these economic losses in many crops, mainly tomato and recently recorded on cucumber. TYLCV was reported as a major pest of tomato and cucumber but it was not characterized at the molecular level. The white-fly was main transmitter of TYLCV. Common symptoms on cucumber plants infected with TYLCV were leaf and fruit deformation, mosaicing, yellowing, upward leaf cupping, stunting. 200 samples of cucumber leaves were collected and the symptoms resulting from viral diseases were recorded and documented. DNA was extracted from 200 infected cucumber leaf samples and PCR detection was performed on 100 samples using two different primer pairs (TY1 and TY2 and TYC1R and TYC1F). PCR tests revealed that 75 samples out of 100 tested samples were positive. Best results were performed by TY1 and TY2 primer pair. Positive samples were stored for further analysis.
Chi-Tai Yeh
Taipei Medical University-Shuang Ho Hospital, Taiwan
Title: Study of expression and functional mechanisms of histamine N-MethylTransferase (HNMT) in tumorigenesis and correlation with progression in lung cancer
Time : 11:30-12:00
Biography:
Chi-Tai Yeh has received his PhD in Food Science and Biotechnology from National Chung Hsing University. He is currently the Research Fellow and Executive Secretary of Department of Research of Taipei Medical University-Shuang Ho Hospital. He has contributed 2 book chapters, published 35 articles in the field of cancer & nutritional chemistry journal and got 2 patents in the medical compound of cancer therapy. His major research interests include cancer cell biology, cancer stem cell research, nutrigenomis and cancer chemoprevention with dietary phytochemicals.
Abstract:
Neuroblastoma (NB) is a common neural crest-derived extracranial solid cancer in children. Among all childhood cancers, NB causes devastating loss of young lives as it accounts for 15% of childhood cancer mortality. Neuroblastoma, especially high-risk stage 4 NB with MYCN amplification has limited treatment options and associated with poor prognosis. This necessitates the need for novel effective therapeutic strategy. JARID1B, also known as KDM5B, is a histone lysine demethylase, identified as an oncogene in many cancer types. Clinical data obtained from freely-accessible databases show a negative correlation between JARID1B expression and survival rates. Here, we demonstrated for the first time the role of JARID1B in the enhancement of stem cell-like activities and drug resistance in NB cells. We showed that JARID1B may be overexpressed in either MYCN amplification (SK-N-BE(2)) or MYCN-non-amplified (SK-N-SH and SK-N-FI) cell lines. JARID1B expression was found enriched in tumor spheres of SK-N-BE(2) and SK-N-DZ. Moreover, SK-N-BE(2) spheroids were more resistant to chemotherapeutics as compared to parental cells. In addition, we demonstrated that JARID1B-silenced cells acquired a decreased propensity for tumor invasion and tumorsphere formation but increased sensitivity to cisplatin treatment. Mechanistically, reduced JARID1B expression led to the down-regulation of Notch/Jagged signaling. Collectively, we provided evidence that JARID1B via modulation of stemness-related signaling is a putative novel therapeutic target for treating malignant NB.
Xiaoyan Jiang
University of British Colombia, Canada
Title: Identification of new microRNA biomarkers in drug-insensitive cancer stem cells in human leukemia
Time : 12:00-12:30
Biography:
Xiaoyan Jiang is a distinguished Scientist in the BC Cancer Research Centre, a Professor in the Department of Medical Genetics and an Associate Member in the Department of Medicine at the University of British Columbia, Vancouver, Canada. Her research interests are focused on basic and translational research of molecular properties of leukemic stem cells that contribute to the development of leukemia and drug resistance. She has been invited to present her work at national and international conferences (>120), to join Editorial Boards of 20 reputed journals and has published more than 100 peer-reviewed publications, review articles and book chapters.
Abstract:
ABL tyrosine kinase inhibitor (TKI) therapies have had a major impact on treatment of chronic myeloid leukemia (CML) worldwide. However, TKI monotherapies are not curative and initial and acquired TKI resistance, as well as relapse, remain challenges. To identify miRNAs in TKI-insensitive CD34+ stem/progenitor cells that might serve as potential biomarkers and/or therapeutic targets; we have used Illumina sequencing to create absolute miRNA expression profiles from treatment-naive CD34+ cells obtained at diagnosis from TKI-responders and non-responders, and normal bone marrow (NBM) as controls. DESeq analysis revealed 66 differentially expressed miRNAs between CML and NBM samples (P<0.05); and 12 between TKI-responders and non-responders. 21 differentially expressed miRNAs were confirmed in CD34+ cells from IM-responders (n=12), non-responders (n=10) and normal individuals (n=11). Importantly, significant changes in some of these miRNAs were detected in CD34+ cells from CML patients (n=65) after 3-month nilotinib (NL) treatment; 19 normalized after NL therapy, whereas 10 showed little change. We also identified differently expressed mRNAs that are predicted targets of the deregulated miRNAs, by comparing RNA-Seq data from the same CML and NBM samples. Strikingly, only 7 differentially expressed mRNAs were predicted targets of the deregulated miRNAs when comparing TKI-responders and non-responders. These miRNAs and their target genes may serve as useful biomarkers to predict clinical response of patients to TKIs and may point to novel therapeutic targets.
Chia-Yen Dai
Kaohsiung Medical University, Taiwan
Title: Dynamics of PBMC gene expression during peginterferon/ribavirin combination therapy in hepatitis C virus genotype 1b-infected patients
Time : 12:30-13:00
Biography:
Chia-Yen Dai has completed his MD and PhD from Kaohsiung Medical University, Kaohsiung, Taiwan. He is the Director of Health Management Center and Department of Occupational and Environmental Medicine, the Visiting Staff of Hepatology Division, Department of Internal Medicine, Kaohsiung Medical University Hospital. He is also a full Professor of College of Medicine, Kaohsiung Medical University. He has published more than 200 papers in reputed journals and has been serving as an Editorial Board Member of medical journals.
Abstract:
Hepatitis C virus (HCV) can replicate in peripheral blood mononuclear cells (PBMCs). This study explored the dynamic gene expression profiles of PBMCs from chronic HCV-1 patients undergoing Peginterferon/Ribavirin (PR) therapy. PBMCs were collected at baseline and on weeks 1 and 4 from 27 chronic HCV-1 patients treated with a 48-week PR regimen (screening dataset n=7; validation dataset n=20). A sustained virologic response (SVR) was defined as undetectable HCV RNA throughout the 24 weeks after the completion of therapy. An Affymetrix microarray was used to identify differentially expressed genes between SVR and non-SVR patients and was validated by quantitative PCR. We found 13 genes at week 1 and 24 genes at week 4 were differentially expressed in the SVR group compared with the non-SVR group. Eight target genes (RSAD2, LOC26010, HERC5, HERC6, IFI44, SERPING1, IFITM3 and DDX60) were selected at week 1 as the major components of a scoring method to predict the treatment outcome for HCV-1 patients. This predictive model reliably stratified the responders and non-responders at week 1 [AUC=0.89, p=0.007 for SVR; AUC=0.95, p=0.003 for complete early virologic response (cEVR)), especially among patients carrying the favorable IL28B rs8099917 TT genotype (AUC=0.89, p=0.002 for SVR; AUC=1.0, p=0.008 for cEVR. The performance of this predictive model was superior to traditional predictors, including the rapid virologic response, viral load and IL28B genotype. We concluded that the genetic model can be used to predict the treatment efficacy of Peginterferon/Ribavirin therapy for HCV-1 patients within one week, especially those carrying the IL28B TT genotype.
Zandisiwe Emilia Magwebu
Medical Research Council, South Africa
Title: Identification of disease causing mutations in hyperglycinemic captive bred vervet monkeys (Chlorocebus aethiops)
Time : 13:45-14:15
Biography:
Zandisiwe Emilia Magwebu is currently a PhD student of South African Medical Research Council through the University of the Western Cape in South Africa. In 2014, she was a part of the Next Generation Scientist (NGS) group at Novartis Pharma, Basel, Switzerland.
Abstract:
High levels of glycine were observed in the plasma (457-795 µmol/L, normal <350 µmol/L) and CSF (7.5-12.7 µmol/L, normal range 3-8) of a small percentage (8%) of captive bred vervet monkeys characterized with total cataract formation at Primate Unit and Delft Animal Centre. Although cataracts have been documented for a variety of primate species, hyperglycinemia as well as this rare and unusual association of conditions have not been reported in the literature before and clearly need elucidation. The purpose of this study was to investigate the disease causing genes in hyperglycinemic vervet monkeys. Eight animals were selected based on their cataract and hyperglycinemic status. The monkeys were assigned into a control and spontaneous (cataract/ hyperglycinemic) group. Gene expression and genotyping experiments were conducted using RNA and DNA samples extracted from blood. Three genes that are associated with nonketotic hyperglycinemia were prioritized, namely: Glycine dehydrogenase (GLDC), aminomethyltransferase (AMT) and Solute Carrier Family 6, Member 9 (SLC6A9). Genotyping analysis of the complete coding sequence of GLDC, AMT and SLC6A9 revealed eight novel single base substitutions of which four were non-synonymous missense and four were silent nucleotide changes. For gene expression, AMT and SLC6A9 were down-regulated in hyperglycinemic monkeys. Therefore, it is possible that GLDC, AMT and SLC6A9 genes may be responsible for hyperglycinemia in captive bred vervet monkeys.
Ali Hosseini Bereshneh
Tehran University of Medical Sciences, Iran
Title: Mutation detection of RB1 tumor suppressor gene (exon 18 & 19) and expression assay of FGF2 oncogene in patients with brain tumors including meningioma and astrocytoma
Time : 14:15-14:45
Biography:
Ali Hosseini Bereshneh has completed his Bsc in Clinical Laboratory Sciences (Medical Technology) from Mashhad University of Medical Sciences and he is currently pursuing MSc in Human Genetics, Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences. He has published more than 15 national and international papers in Iranian and international journals. He has published 5 national books in the area of Medical Genetics, Genetics of Dentistry and Prenatal Diagnosis & Genetic Counseling. He is a Member of Iranian Medical Genetics Society and Medical Laboratory Society.
Abstract:
Most studies have shown that there are association between the development and malignancy of brain tumors and tumor suppressor genes and oncogenes. The aim of this project is to investigate the RB1 gene mutations in exon 18 and 19 and FGF2 oncogene expression in patients with Astrocytoma and Meningioma type’s brain tumor. This is an in vitro study in which the extraction of DNA from 20 samples of fresh brain tissue was performed by phenol-chloroform protocols. After PCR amplification of exon 18 and 19 of RB1 gene, screening by SSCP (Single-Strand Conformation Polymorphism) was performed to detect the possible shifts. Those shifts were sequenced. Then the cells were extracted from fresh brain tissue for analysis of FGF2 gene expression by flow cytometry. In this study was detected two unknown variation (Heterozygote Substitution) in intronic regions including c.1815-170T>G and c.1960+107T>G; and one insertion mutation in intronic region c.1960+108_1960+109isnT. It was observed that FGF2 gene expression in astrocytoma samples was increased. Findings from this study were indicated that mutations in RB1 gene mostly was in malignant astrocytoma brain tumor type; also, since the FGF2 gene expression in astrocytoma brain tumors was higher than benign meningioma type of brain tumors. Overexpression of FGF2 gene may play an essential role in malignant brain tumor and this may be important in diagnosis and new therapeutic methods of brain tumors treatment.
Reyhane Sadat Saeedi
Tehran University of Medical Sciences, Iran
Title: The role of chromosomal abnormalities in spontaneous abortion and chromosome analysis importance
Time : 14:45-15:15
Biography:
Reyhane Sadat Saeedi is currently a student in Faculty of Medicine, Tehran University of Medical Sciences, Iran. She is a Member in Students' Scientific Research Center and Student Advisory Committee of Medical School of Tehran University of Medical Sciences. She has published 3 papers in reputed journals.
Abstract:
Spontaneous abortions define as a loss of pregnancy before 20 week of gestation. About 50% spontaneous abortion of first trimester of pregnancy results from chromosomal abnormalities. Understanding of these genetic causes is absolutely important in born of healthy infants and will contribute to the management of subsequent pregnancies. Fetal aneuploidy or monosomy and trisomy of fetus caused upset to the natural process of fetal development and eventually lead to miscarriage. In the most cases, these aneuploidies result from error in the disjunction of gamete chromosomes and the risk of recurrence is low. All symptoms of these disorders are due to dosage of gene expression. Enhanced maternal age increases damage to ovum and heightens the risk of miscarriage and birth defects. The importance of genetic analysis in miscarriage is evident when carrier parents of balanced rearrangement experience recurrent abortions. These parents have a normal phenotype but have susceptibility to produce unbalanced gametes that can leads to miscarriage. Due to the possibility of being parent’s carrier, chromosome analysis and risk assessment are crucial for understanding of recurrence risk. Chromosomal analysis in aborted fetuses is risk assessment of recurrent abortion in subsequent pregnancy. Actually utilization of genetic counseling and knowing the causes of abortion and genetic bases of this condition will be helpful in management of subsequent pregnancies and birth of healthy newborns. In addition, peer understanding of spontaneous abortion genetic causes could be helpful in better utilize of diagnostic and therapeutic approaches of assisted reproduction.
Saeed Tarverdizadeh
Tehran University of Medical Sciences, Iran
Title: Pharmacogenetics in breast cancer therapy: Patient’s genetics profile in trastuzumab and tamoxifen prescription
Time : 15:15-15:45
Biography:
Saeed Tarverdizadeh is currently a student in Faculty of Medicine, Tehran University of Medical Sciences, Iran. He is also a Member of Students' Scientific Research Center. He has published 3 papers in reputed journals.
Abstract:
Breast cancer that is caused by the accumulation of genetic and epigenetic factors, is one of the main causes of death resulted from cancer. Various therapeutic ways have been introduced for this cancer and the traditional diagnosis and treatment is based on the prognosis estimation using cancer anatomic features (TNM system) and clinical results, but studies show the different responses of these treatments and recurrence after those in some patients. This diversity has resulted by the difference in biological and molecular characteristics. So genomic and molecular studies became more important and the role of targeted treatment based on an individual's genome was highlighted. Today, the progress in personalized medicine using specific individual genome profile has been possible. The ultimate goal of such studies, in the setting of the personalized medicine is providing markers which can be used to risk assessment of progressing disease. This new science cause great development in the treatment of breast cancer by recognition of specific markers and application of targeted treatment like monoclonal antibodies which Trastuzumab and Tamoxifen are the most common examples. The aim of this review is to describe the different aspects of personalized medicine in the breast cancer treatment.
- posters
Location: Golden Tulip Berlin - Hotel Hamburg
Session Introduction
Qu Zhengzhong James
Genome Institute of Singapore, Singapore
Title: Development of a comprehensive high-coverage, cost effective HLA typing assay
Biography:
Qu Zhengzhong James has completed his PhD from the Chinese University of Hong Kong, Department of Chemical Pathology. He is the laboratory Manager of the POLARIS (Personalized OMIC Lattice for Advanced Research and Improving Stratification), a strategic program to pilot the application of clinical genomics in the treatment and diagnosis of medical diseases in Singapore and the region. His job responsibility is to make sure all the testing procedures in the lab will meet the requirements from Singapore Ministry of Health and also meet the guidelines from the College of American Pathologists.
Abstract:
The human leukocyte antigen (HLA) is responsible for regulation of the immune system in humans. HLA typing has important clinical significance for tissue transplantation matching, autoimmune disease-association studies and drug hypersensitivity research. However, the highly polymorphic essence of the HLA genes makes it a challenging task. Conventional methods like SSO and SSP only provide lower resolution typing results and cannot identify new alleles. High-resolution techniques like SBT required other methods for confirmation of phasing and it is time consuming. Single Molecule Real Time (SMRT) sequencing is a parallelized single molecule DNA sequencing by synthesis technology developed by Pacific Biosciences. It has long read lengths which enable unambiguous phasing of the entire HLA genes. However, the cost of the SMRT sequencing is still too high for clinical routine use. To develop clinically implementable HLA typing assay by using SMRT sequencing technology, we designed two sets of multiplex PCR primers for the HLA genes. The first assay we developed enables the HLA typing of A, B, C, DRB1, DQB1, DQA1, DPA1 and DPB1 genes for one patient by using one SMRT cell. The second assay we developed enables the typing of HLA-A genes for up to 50 patients by using one SMRT cell. Our assays provided choice of both coverage and cost-effectiveness.
Qiong Shi
Shenzhen University, China
Title: High throughput identification of novel conotoxins from cone snails by multi-transcriptomic sequencing
Biography:
Qiong Shi has completed his PhD from China Zhongshan University and Postdoctoral studies from Beijing Normal University and Japan Hokkaido University. Before joining BGI in 2011, he has worked at USA National Institutes of Health, University of Maryland and OriGene Technologies Inc. He is the Dean of BGI Academy of Marine Sciences, VP and Chief Scientist of BGI Fisheries, a Genomics Professor at University of Chinese Academy of Sciences and Shenzhen University and the Chief of Shenzhen Key Lab of Marine Genomics. He has published over 60 academic papers and 6 monographs and acquired 12 Chinese patents.
Abstract:
With an estimation of over 500 species, cone snails are classified into Conus, the biggest genus among marine invertebrates. Cone snails apply a complex cocktail of venom components to capture and digest prey. According to variation in diet, cone snails are divided into piscivorous, molluscivorous and vermivorous groups. In the past few years, our lab has successfully performed transcriptomic sequencing of around 10 species. Here, we summarize our recent data about a special species, Chinese tubular cone snail (C. betulinus), which is the dominant conus species inhabiting the South China Sea. The transcriptomes of venom ducts and venom bulbs from a variety of specimens of this species were sequenced using both next-generation sequencing and traditional Sanger sequencing technologies, resulting in identification of a total of 215 distinct conopeptides. Among these, 183 were novel conopeptides, including 9 new super families. It appears that most of the identified conopeptides are synthesized in the venom duct, while a handful of conopeptides are identified only in the venom bulb and at very low levels. Variation in conopeptides from different specimens of C. betulinus was observed, which suggested the presence of intraspecific variability in toxin production at the genetic level. These novel conopeptides provide a potentially fertile resource for development of new pharmaceuticals and a pathway for discovery of new conotoxins.
Tianbo Jin
Xizang Minzu University, China
Title: Genetic polymorphisms of pharmacogenomic VIP variants in seven national minorities from different regions of China
Biography:
Tianbo Jin has completed his PhD from Xi’an Jiaotong University and Postdoctoral studies from Brown University, School of Medicine. He is the Deputy Director of Key Laboratory for Molecular Genetic Mechanisms and Intervention Research on High Altitude Disease of Tibet Autonomous Region. He has dedicated to Pharmacogenomics for several years and published more than 100 papers in SCI journals.
Abstract:
Pharmacogenomic variant information is well known for major human populations; however, this information is less commonly studied in minorities. We genotyped 85 very important pharmacogenetic (VIP) variants (selected from the PharmGKB database) in the Tibetan, Uygur, Miao, Li, Deng, Kyrgyz, Ihoba populations and compared our data with other major eleven populations from the HapMap data set, including ASW, CEU, CHB, CHD, GIH, JPT, LWK, MEX, MKK, TSI and YRI. We also downloaded SNP allele frequencies from the Allele Frequency Database to observe the global genetic variation distribution for these specific loci. Through statistical analysis, we found that genotype frequencies of ADH1B, AHR, CYP3A5, PTGS2, VDR, MTHFR and VKORC1 in our study populations differed widely from those in the 11 HapMap populations. Population structure and F-statistics (Fst) analysis also showed significant differences between these seven minorities and other HapMap populations. Our results complement the information provided by the database of pharmacogenomics on Tibetan, Uygur, Miao, Li, Deng, Kyrgyz, Ihoba populations. We provide a theoretical basis for safer drug administration and individualized treatment plans for these seven populations. We also provide a template for the study of pharmacogenomics in various ethnic minority groups in China.
Chi-Un Pae
Catholic University of Korea, South Africa
Title: Genes involved in neurodevelopment, neuroplasticity and bipolar disorder: CACNA1C, CHRNA1 and MAPK1
Biography:
Chi-Un Pae has completed his PhD from Catholic University of Korea (CUMC), South Korea. He is the Principal Investigator of Depression Research Center, funded by Korean Government. He has published more than 334 papers in reputed journals and has been serving as an Editorial Board Member of repute.
Abstract:
Bipolar disorder (BPD) is a common and severe mental disorder. The involvement of genetic factors in the pathophysiology of BPD is well known. In the present study we tested the association of several SNPs within three strong candidate genes, CACNA1C, CHRNA7 and MAPK1, with BPD. These genes are involved in monoamines-related pathways as well as in dendrites development, neuronal survival, synaptic plasticity and memory/learning. 132 subjects diagnosed with BPD and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within CACNA1C, CHRNA17 and MAPK1. Distribution of alleles and block of haplotypes within each gene were compared in cases and controls. Interactions between variants in different loci were also tested. Significant differences in the distribution of alleles between the cases and controls where detected for rs1016388 within CACNA1C, rs1514250, rs2337980, rs6494223, rs3826029 and rs4779565 within CHRNA7 and rs8136867 within MAPK1. Haplotype analyses also confirmed an involvement of variations within these genes in BPD. Finally, exploratory epistatic analysis demonstrated potential interactive effects, especially regarding variations in CACNA1C and CHRNA7. Overall, our data suggest a possible role of these three genes in BPD. Alterations of one or more common brain pathways (e.g. neurodevelopment, neuroplasticity and calcium signaling) may explain the obtained results. However, a limited sample size and the consequent risk of false positive findings should be carefully taken into consideration when evaluating these results.
Mohammad Roushanghalb
Tehran University of Medical Sciences, Iran
Title: PDCD1 single nucleotide genes polymorphisms confer susceptibility to juvenile-onset systemic lupus erythematosus
Biography:
Mohammad Roshanghalb is currently a Medical Intern of Imam Khomeini Hospital Complex, Faculty of Medicine, Tehran University of Medical Sciences, Iran. He is also a Member of Students' Scientific Research Center.
Abstract:
Juvenile-onset systemic lupus erythematosus (JSLE) is a multisystem autoimmune disease in which both the genetic and environmental factors seem to be involved in the etiopathogenesis of the disease. The aim of this study was to evaluate the association of programmed cell death 1 (PDCD1, also called PD-1) gene polymorphisms with JSLE susceptibility in Iranian population. In this case-control association study, three PDCD1 SNPs, including PD-1.1 G/A, PD-1.3 G/A and PD-1.9 C/T were genotyped in 50 Iranian patients with JSLE and 202 healthy unrelated controls using PCR-RFLP method. The PD-1.1 A allele was found to be more frequent in the case group compared with controls (6% vs. 1.5%, p=0.024). Moreover, the GG genotype was less frequent in cases than in controls (88% vs. 97%, p=0.021). The other PDCD1 SNPs did not show association. At the haplotypic level, no significant differences was recognized between the two groups of case and control neither for the GAC (PD-1.1 G, PD-1.3 A, PD-1.9 C) nor for the GGC haplotype (PD-1.1 G, PD-1.3 G, PD-1.9 C). Our findings support the influence of the PD1.1 A SNP on the development of JSLE in Iranian population.
Reyhane Sadat Saeedi
Tehran University of Medical Sciences, Iran
Title: Recent progression in hemophilia gene therapy
Biography:
Reyhane Sadat Saeedi is currently a student in Faculty of Medicine, Tehran University of Medical Sciences, Iran. She is a Member in Students' Scientific Research Center and Student Advisory Committee of Medical School of Tehran University of Medical Sciences. She has published 3 papers in reputed journals.
Abstract:
Hemophilia is a bleeding disorder in which coagulation is corrupted. There are different types of Hemophilia, more than 400,000 people around the world living with the disease. Two common types of hemophilia are A and B, defects in coagulation factors 8 and 9 respectively. Hemophilia A is 80-85% of cases. Coagulation factors 8 and 9 located at the long arm of chromosome X and mutations in these genes result in the defective production of coagulation factors. Hemophilia considered an appropriate target for gene therapy, because production of 1% of normal level could adjust the phenotypic problems. Various methods have been developed for hemophilia gene therapy, producing coagulation factors in the patients ultimately. Injection of coagulation factor gene by vector into the stem cells extracted from the patients or vectors containing the transgene insertion into differentiated cells with long survival, such as muscle cells and liver are among the most important of these methods. As well as the most recent methods of gene therapy, gene transfer based on induced pluripotent stem cells is abbreviated iPS. Hepatocytes a very suitable target cells for hemophilia gene therapy because these cells are the main site of synthesis of coagulation factors. Muscle cells also are suitable for the injection of transgenes in gene therapy for hemophilia because of its appropriate secretory power and its availability. The most important and most widely used viral vectors for gene therapy of hemophilia are retroviral vectors and lentiviral and Adeno-associated viruses.
Saeed Tarverdizadeh
Tehran University of Medical Sciences, Iran
Title: Autosomal recessive non syndromic hearing loss (ARNSH): Different mutations spectrum in Iran
Biography:
Saeed Tarverdizadeh is currently a student in Faculty of Medicine, Tehran University of Medical Sciences, Iran. He is also a Member of Students' Scientific Research Center. He has published 3 papers in reputed journals.
Abstract:
Sensorineural hearing loss is the most common disorder in humans that heterogeneity is high, and one out of every 1,000 to 2,000 newborns, affected by sensorineural hearing loss. More than 50 percent of the causes of deafness have been attributed to genetic factors. Non-syndromic hearing loss include more than 70 percent of cases of hereditary deafness; which 85% of NSHL have autosomal recessive hereditary pattern. So far, more than 100 loci for this type of hearing loss are estimated. Nuclear and mitochondrial gene mutations can cause this disease. Of which DFNB1 locus is responsible for half of recessive deafness; including transfer protein genes and ion channel protein like connexin 26 and 30. In Iran, this locus is a primary cause of hearing loss. GJB2 mutations especially 35del G play important role in developing hearing loss in Iran. After that, mutations in SLC26A4 gene in DFNB4 locus are the second cause of ARNSH in our country. The next locus to study could be DFNB59 that contains PJVK gene and it is highly prevalent in Iran. Also mutations in mitochondrial genes such as 12S rRNA genes are involved in development of pre lingual non-syndromic hearing loss.
- B2B and Networking Session