Day 1 :
Keynote Forum
Henry M. Sobell
University of Rochester, USA
Keynote: The centers of premeltons signal the beginning and ends of genes
Time : 10:00-10:45
Biography:
Henry M Sobell completed his studies at Brooklyn Technical High School (1948-1952), Columbia College (1952-1956), and the University of Virginia School of Medicine (1956-1960). Instead of practicing clinical medicine, he then went to the Massachusetts Institute of Technology (MIT) to join Professor Alexander Rich in the Department of Biology (1960-1965), where, he had a Helen Hay Whitney Postdoctoral Fellowship where he learned the technique of single crystal X-ray analysis. He then joined the Chemistry Department at the University of Rochester, having been subsequently jointly appointed to both the Chemistry and Molecular Biophysics departments (the latter at the University of Rochester School of Medicine and Dentistry), becoming a full tenured Professor in both departments (1965-1993). He is now retired and living in the Adirondacks in New York, USA.
Abstract:
Premeltons are examples of emergent structures (i.e., structural solitons) that arise spontaneously in DNA due to the presence of nonlinear excitations in its structure. They are of two kinds: B-B (or A-A). Premeltons form at specific DNA-regions to nucleate site-specific DNA melting. These are stationary and, being globally non-topological, undergo breather motions that allow drugs and dyes to intercalate into DNA. B-A (or A-B) premeltons, on the other hand, are mobile, and being globally topological, act as phase-boundaries transforming B- into A- DNA during the structural phase-transition. They are not expected to undergo breather-motions. A key feature of both types of premeltons is the presence of an intermediate structural-form in their central regions (proposed as being a transition-state intermediate in DNA-melting and in the B- to A- transition), which differs from either A- or B- DNA. The so called beta-DNA, this is both metastable and hyperflexible–and contains an alternating sugar-puckering pattern along the polymer-backbone combined with the partial-un-stacking (in its lower energy-forms) of every other base-pair. Beta-DNA is connected to either B- or to A- DNA on either side by boundaries possessing a gradation of nonlinear structural-change, these being called the kink and the anti-kink regions. The presence of premeltons in DNA leads to a unifying theory to understand much of DNA physical-chemistry and molecular-biology. In particular, premeltons are predicted to define the 5’ and 3’ ends of genes in naked-DNA and DNA in active-chromatin, this is having important implications for understanding physical aspects of the initiation, elongation and termination of RNA-synthesis during transcription. For these and other reasons, the model will be of broader interest to the general audience working in these areas. The model explains a wide variety of data, and carries within it a number of experimental predictions –all readily testable – as will be described in my talk.
Recent Publications
1. Sobell H M (2016) Premeltons in DNA. Journal of Structural and Functional Genomics 17:17-31.
2. Sobell H M (2009) Premeltons in DNA. A unifying polymer-physics concept to understand DNA physical-chemistry and molecular-biology. Explanatory publications, Lake Luzerne, NY, ISBN 978-0-615-33828-6.
3. Sobell HM (2013) Organization of DNA in Chromatin. Rather than bending uniformly along its length, nucleosomal DNA is proposed to consist of multiple segments of B- and A- DNA held together by kinks when forming its left-handed toroidal superhelical structure. Explanatory publications, Lake Luzerne, NY, ISBN 978-0-692-01974-0.
Keynote Forum
Hiltrud Brauch
Dr. Margarete Fischer Bosch-Institute of Clinical Pharmacology, Germany
Keynote: Tamoxifen pharmacogenomics of breast cancer: the controversy and way forward
Time : 10:45-11:30
Biography:
Hiltrud Brauch has completed herPhDat the University of Heidelberg, Germany, and postdoctoral studies as a Fogarty International Visiting Fellowat the National Institutes of Health (NIH), National Cancer Institute (NCI), Frederick, Maryland, USA. She is the deputy director of Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology in Stuttgart, a non-profit private research institute of the Robert Bosch Foundation. She has published more than 250 papers in reputed journals and has been serving as an editorial board member of Pharmacogenetics and Genomics as well as Pharmacogenomics and Personalized Medicine.
Abstract:
Breast cancer is a global health burden with 1.7 million newly diagnosed patients and more than half a million patients dying from the disease each year. The large majority (75%) of breast cancers express the estrogen receptor (ER) making them amenable to targeted endocrine therapy. Standard of care is the blockade of estrogen signaling via long-term estrogen deprivation. Two proven treatment options are available: tamoxifen, a selective ER modulator which blocks 17ß-estradiol binding to ER to stop tumor growth, and aromatase inhibitors (AI), which block the aromatase enzyme that prevents the conversion of androgens to estrogens. Despite the well-established effectiveness of endocrine treatments every other patient displays de novo or acquired resistance which ultimately leads to disease progression and death. Based on its well-known metabolism and drug action, tamoxifen has been in the spotlight of pharmacogenomics investigations within the past decade. The goal is to identify biomarkers that can predict tamoxifen outcome and facilitate personalized treatment schemes in order to avoid drug failure. Tamoxifen failure has been in part attributed to a lack of bio-activation towards its active metabolite, endoxifen. Pharmacological and pharmacogenetics evidence strongly support the view that in vivo endoxifen formation is mainly mediated from the primary metabolite N-desmethyl-tamoxifen by the polymorphic cytochrome P450 (CYP) 2D6 enzyme. Distinct genetically determined functional CYP2D6 variants are present in the general population and inter-individual differences in enzyme activities can be grouped into the four CYP2D6 phenotypes ultra-rapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizers. We and others provided strong evidence that tamoxifen treated EM breast cancer patients have high levels of endoxifen and that they are likely to benefit from the treatment. In contrast, PM patients have low endoxifen levels and a significant risk to relapse. Thus, CYP2D6 polymorphism and plasma endoxifen levels have a great potential as suitable tamoxifen outcome predictors. However, due to controversies from negative studies, the translation into the clinic has been hampered. In my talk, I will discuss the current status of the debate and emphasize the need for uniform study design, technology and statistical procedures in the conduct of pharmacogenomics analyses in order to avoid shortcomings and delay in clinical implementation. Moreover, I will present a way forward towards the clarification of the CYP2D6 tamoxifen pharmacogenomic issue via a novel strategy for the optimization of endoxifen plasma levels in CYP2D6 compromised breast cancer patients currently investigated in our ongoing phase II clinical trial.
- Cancer Genomics| Functional Genomics| Next Generation Sequencing |Biomarkers| Pharmacogenomics | Proteomics| Clinical Genomics| Human Genomics | Genome Engineering
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Session Introduction
Jatinder Lamba
University of Florida, USA
Title: Integrated genetic and epigenetic analysis identifies biomarkers of prognostic significance in pediatric acute myeloid leukemia
Time : 11:45-12:15
Biography:
Jatinder Lamba is an Associate Professor in Department of Pharmacotherapy and Translational Research. She completed her PhD in the field of Pharmacogenomics at Postgraduate Institute of Medical Education and Research in Chandigarh, India and Post-doctoral training at St. Jude Children’s Research Hospital, Memphis. Her research has been funded from NIH/NCI since 2008 and focuses on “Identification, characterization and clinical validation of genomic/epigenomic markers predictive of therapeutic outcome in cancer patients specifically Acute Myeloid Leukemia. Her research spans from preclinical basic research comprising the discovery phase to translational/clinical phase in patient populations from multi-institute clinical trials.
Abstract:
Epigenetic mechanisms such as DNA methylation are deregulated in cancer. Aberrant DNA methylation is reported to have clinical significance in acute myeloid leukemia (AML) in adults; however, its impact on pediatric AML is relatively unknown. Our research focuses on integrated genome-wide DNA methylation and gene expression analyses to identify the epigenetic signatures that are associated with gene expression and prognosis in pediatric patients with AML. We developed and applied a novel method that integrates canonical correlation analysis with projection onto the most interesting statistical evidence (CC-PROMISE) to identify genes with methylation and expression values that exhibit a biologically concordant and clinically meaningful pattern of associations’ treatment outcome in pediatric AML patients. Our results identified several genes of significant importance in cell growth, proliferation, apoptosis as well as AML biology as top candidates. Of special interest was the gene DNA methyl-transferase gene DNMT3B, which has been previously implicated in adult AML, significant methylation-expression correlation and was strongly predictive of poor outcome in pediatric AML. Furthermore, consistent with its biological function, greater DNMT3B expression associated with greater genome-wide methylation burden. Collectively, these results indicate that deregulated methylation of the DNMT3B locus may modulate DNMT3B expression which subsequently alters the methylome, transcriptome, disease progression, and clinical prognosis of childhood AML. Overall understanding epigenetic and transcriptomic landscape of childhood AML can help in better designing the incorporation of epigenetic modifier drugs to standard chemotherapy regimens as well as help in identifying patients that would likely be better candidates to receive such a combination treatment.
Yong Yu
Wellcome Trust Sanger Institute, United Kingdom
Title: Single cell RNA sequencing analysis of bone marrow innate lymphoid progenitors
Time : 12:15-12:45
Biography:
Yong Yu did his PhD training with Dr Pentao Liu, Wellcome Trust Sanger Institute where he focused on the role of Bcl11a in early lymphocyte cell development (2010-2012). Subsequently, he was recruited by Dr Pentao Liu as a Postdoctoral Research Fellow to continue to explore the molecular and cellular mechanisms of hematopoiesis. Recently, he transcriptomically profiled hundreds of innate lymphoid progenitors at the single cell level and discovered PD-1hi marks ILC progenitors and effectors. This work was published in Nature.
Abstract:
Innate lymphoid cells (ILCs) are a new family of immune cells and play fundamental roles in the development of immune system and protect host from pathogens infection but ILC progenitor development in the bone marrow was not clear. We used single cell RNA sequencing to dissect BM ILC progenitors and identified PD-1 marked a committed ILC progenitor. We further found that activated ILCs in particular ILC2s expressed high levels of PD-1. Indeed, depleting PD-1-high ILC2s substantially reduced type 2 cytokines in immune responses, and inhibited acute lung inflammation induced by papain. Our data therefore demonstrate the value of single cell RNA sequencing in dissecting development and present a new perspective for targeting PD-1 in immunotherapies.
Rozana Oliveira Goncalves
Gonçalo Moniz Research Center, Brazil
Title: Pharmacogenetics: advanced drug administration
Time : 12:45-13:15
Biography:
Rozana Oliveira Goncalves is currently a Biology Teacher in the city of Salvador in Brazil. In 1997, she completed a course in Biological Sciences at Catholic University of Salvador. In 2001, she began her career in research as an intern in the Laboratory of Human Genetics and at Maternidade Climério de Oliveira. In 2006, she started her Master's degree in Biotechnology and Investigative Medicine at Gonçalo Muniz Research Center/Fiocruz. She has experience in Genetics, working mainly in the following subjects: “Occupational exposure, bio-indicators, exchanges between chromatid sisters, and recurrent abortion”.
Abstract:
Adverse drug reactions are influenced by multiple factors, including health, environmental influences and genetic characteristics. Pharmacogenetics studies how inter-individual genetic variations may affect drug responses. It is the technology that researches the influence of genetic variation on drug response in patients by correlating gene expression or polymorphisms with a drug's efficacy or toxicity. It is well known that Adverse Drug Reactions (ADRs) are a relevant health matter, being the fourth cause of demise in hospitalized patients. Important drug agencies have demonstrated a great interest in the early detection of ADRs due to their high incidence and increasing health care costs. Pharmacogenetics aims to develop the means to optimize drug therapy with respect to the patients’ genotype, to ensure maximum efficacy with minimal adverse effects. Pharmacogenetics is a research field still in development and therapy individualization remain a challenge for the future. It is important to appreciate that many genes may influence the response to drugs, and the genetic polymorphisms present ethnic variation, which complicates the identification of genetic variations which are most relevant. Clinical validation of genetic markers of the greatest clinical relevance is perhaps one of the major limiting factors in the use of genetic information when making treatment decisions.
Anat Achiron
Tel-Aviv University Sackler School of Medicine, Israel
Title: From translational research to a new molecule for the treatment of multiple sclerosis
Time : 14:00-14:30
Biography:
Anat Achiron is a full Professor of Neurology at Tel-Aviv University, Sackler School of Medicine and Director of the Multiple Sclerosis Center at Sheba Medical Center, Israel. Her research interests are within the fields of Gene Expression and Neuro-immunology in relation to multiple sclerosis. She has extensively studied biological markers in the very early stages of the disease and is involved in studies evaluating disease related outcome variables and prediction of disease activity and treatment response. She has published over 200 publications in the scientific literature and received numerous grants and scientific awards.
Abstract:
Applying high throughput gene expression microarrays, we identified that suppression of RNA polymerase 1 (POL1) pathway is associated with benign course of multiple sclerosis (MS). This finding supported the rationale for direct targeting of POL1 transcription machinery as an innovative strategy to suppress MS. Benign multiple sclerosis (BMS) occurs in about 15% of patients with relapsing-remitting MS (RRMS) that over time do not develop significant neurological disability. Aim of this study is to evaluate the biological mechanisms associated with and analyzed by Partek and pathway reconstruction performed by Ingenuity software the most informative genes. BMS signature was enriched by genes related to POL1 transcription that result in activation of the apoptotic cell death machinery. Verification of POL1 pathway key genes RRN3, POLR1D, and LRPPRC was confirmed by qRT-PCR, and RRN3 silencing resulted in significant increase in the apoptosis level of peripheral blood mononuclear cells sub-populations in RRMS patients. To target POL1 transcription machinery as a new strategy for suppression of MS disease activity, we developed and synthetized an oral POL1 inhibiting compound RAM-589.555, that selectively suppressed ribosomal biogenesis of activated immunocompetent cells. RAM-589.555 demonstrated high permeability, specificity to POL1 pathway, ability to induce apoptosis and to inhibit proliferation and viability of activated lymphocytes both in vitro and in vivo. Moreover, oral administration of RAM-589.555 blocked ribosomal RNA transcription and significantly suppressed and ameliorated experimental autoimmune encephalomyelitis the animal model of MS. Our findings demonstrate the application of translational research to target a new molecule for the treatment of MS.
Gurevich Michael
Multiple Sclerosis Center, Sheba Medical Center, Israel
Title: Optimizing multiple sclerosis diagnosis using gene expression and genomic association data
Time : 14:30-15:00
Biography:
Gurevich Michael is the Head of the Neuro-genomics Laboratory at Sheba Multiple Sclerosis Center, Israel. His research primarily focuses on “The study of translational medicine and functional genomics in neurological diseases and multiple sclerosis”. He has gained extensive knowledge and experience working with DNA microarray technology, discovering multiple sclerosis related molecular disease pathogenesis and finding biomarkers that may assist in disease diagnosis, monitoring and prognosis of clinical outcome.
Abstract:
The diagnosis of multiple sclerosis (MS) is based on the neurological symptomatology in combination with the presence of central nervous system lesions disseminated in time and space. However, the clinical, imaging and/or laboratory findings of patients with MS may mimic a wide array of other vascular, inflammatory and demyelinating diseases, hereby defined as NonMS. This overlap may pose a significant diagnostic challenge especially in the process of diagnosis at the early disease stage. We utilized findings of large-scale Genome Wide Association Studies (GWAS) to develop a blood gene expression based classification tool to assist in the diagnosis during the first demyelinating event suggestive of MS. We merged knowledge of 110 MS susceptibility genes gained from MS GWAS studies together with our experimental results of differential blood gene expression profiling between 80 MS patients and 31 NonMS patients. Multiple classification algorithms were applied to this cohort to construct a diagnostic classifier that correctly distinguished between MS and NonMS patients. The overall accuracy of the constructed 42-gene classifier was tested on an independent patients population consisting of diagnostically challenging cases including NonMS patients with positive MRI findings and achieved a correct classification rate of 76.0±3.5%. The presented diagnostic classification tool complements the existing diagnostic McDonald criteria by assisting in the accurate exclusion of other neurological diseases at presentation of the first demyelinating event suggestive of MS.
Hanadi Al-Hashash
Kuwait Institute for Scientific Research, Kuwait
Title: Characterizing TYLCV in cucumber through the application of molecular techniques
Time : 15:00-15:30
Biography:
Hanadi K Al-Hashash completed her Graduation at Kuwait University. She completed her BSc in Microbiology (major) and Biochemistry (minor), then joined Kuwait Institute for Scientific Research (KISR) since May, 2001 till present. Since then, she worked as a task Leader in several project within Biotechnology program. She leads one general research activity (FB067G). She has an excellent experience in “Microbial isolation and identification using conventional as well as molecular techniques, DNA, RNA, and protein extraction, using restriction enzymes, and using ELISA”.
Abstract:
Cucumber is one of the most important vegetable crops in Kuwait, but unfortunately dramatic losses were recorded during the growing season. The majority of these losses are caused by viral infections. Mixed viral infections were reported in cucumber and the main one which was Tomato yellow leaf curl virus (TYLCV). Molecular study was carried on to certify and diagnose the viral infections on cucumber and the study started with characterizing TYLCV. During the study, 50 samples of cucumber leaves were collected, and the symptoms resulting from viral diseases were recorded and documented. DNA extraction and polymerase chain reaction (PCR) tests were performed on the collected samples. PCR tests revealed that 40 out of the 50 samples were positive for the presence of TYLCV. TYLCV was characterized and reported to be infecting cucumber crops which was only reported in tomato crops, which revealed the second report of TYLCV on cucumber in the world.
- Micro RNA | mRNA Analysis | Bioinformatics in Genomics | Comparative Genomics | Microbial Genomics | Plant Genomics | Future trends in Genomics | Genome Medicine | Genomics Market
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Session Introduction
Gregg S. Pettis
Louisiana State University, USA
Title: Phenotypic and transcriptomic analyses of colonial phase variants of the cholera pathogen vibrio choleraeReveal a novel biofilm-defective form
Time : 11:15-11:45
Biography:
Gregg S Pettis completed his PhD at University of Missouri and Post-doctoral fellowship in Department of Genetics at Stanford University School of Medicine. He is an Associate Professor in Department of Biological Sciences at Louisiana State University. He has published more than 30 papers in peer-reviewed journals, and his research has been supported by the National Science Foundation, United States Department of Agriculture, and the National Oceanic and Atmospheric Administration. He is an Editorial Board Member of Applied and Environmental Microbiology journal and is the Editor of the microbiology section of the Encyclopedia of Life Sciences.
Abstract:
In a process termed phase variation, the marine bacterium and cholera pathogen Vibrio cholerae alternately expresses smooth or rugose colony types, with the latter linked to sophisticated biofilm architecture and a greater resistance to environmental stress. To assess transcriptome changes in response to phase variation in V. cholerae O1 El Tor pandemic strain N16961, we compared the transcriptome obtained by RNA-seq among the smooth parent N16961, its rugose derivative (N16961R) and smooth isolates obtained directly from the rugose at high frequencies consistent with phase variation (N16961SD). Phenotypic characterization of these isolates, including the ability to form pellicles and produce biofilm, was also performed. Differentially regulated genes were revealed for various cellular functions, including acetate metabolism, gluconeogenesis, and anaerobic respiration, suggesting critical links between these processes and biofilm formation in this organism. Principal component analysis separated the transcriptome of the novel phase variant form N16961SD from the other phase variants entirely. Unexpectedly, although N16961SD produced no detectable biofilm, transcription of its biofilm genes was elevated similar to N16961R. Other transcriptome signatures involving two-component signal transduction, c-di-GMP synthesis, chemotaxis, and environmental persistence were also shared between N16961R and N16961SD. These share signatures may implicate a stress adaptation in the pathogen that facilitates transition of the N16961SD smooth form back to rugosity. We are currently exploring the genetic or epigenetic basis of this unusual biofilm-defective N16961SD isolates so that we may more fully understand their role in the ecology and potentially the pathogenesis of V. cholerae.
Martine Hamann
University of Leicester, United Kingdom
Title: Identification of microRNAs signature and signalling pathway targets in an animal model of tinnitus
Time : 11:45-12:15
Biography:
Martine Hamann is an Associate Professor of Neurosciences in Department of Neurosciences, Psychology and Behavior at University of Leicester, UK. She completed her Graduation and PhD in Neurosciences at University of Strasbourg (France) and Centre Medical Universitaire (Geneva, Switzerland). She has completed her Post-doctoral studies at University College London. Her research focuses on “Understanding cellular mechanisms associated to hearing loss and tinnitus in pre-clinical models, and aims at identifying markers to prevent and/or target those auditory deficits”.
Abstract:
Tinnitus, the pathological percept of phantom sound, is a highly prevalent disorder, affecting 10 to 15% of the population worldwide. Tinnitus can be triggered by prolonged exposure to loud noise damaging cochlear hair cells and introducing excitability changes in the auditory brainstem. There is no sensitive biomarker for diagnosis or early detection of tinnitus. MicroRNAs are approximately 22-nt RNA segments that are involved in the regulation of protein expression primarily by binding to one or more target sites on an mRNA transcript and inhibiting translation. MicroRNAs are highly stable and have been recently described as powerful biomarkers in a wide range of diseases. The study aims at identifying microRNAs present during tinnitus, assessed in CBA mice using the gap-prepulse inhibition of the acoustic startle reflex, a broadly applied paradigm to study changes in neural processing related to tinnitus. We demonstrate selective gap detection deficits in CBA mice 3-4 weeks following acoustic over-exposure and identify specific modulation of microRNA levels in the brainstem and blood in those tinnitus positive CBA mice. Using the database DIANA-TarBase v7.0 (1), we show that most regulated microRNAs (e.g. miR-128-3p, miR-140-5p, miR-151-5p and miR-204-5p) are involved in fatty acid metabolism and steroid signaling. The present results have important implications toward understanding tinnitus pathophysiology and designing novel pharmacotherapies targeting the function of those microRNAs.
Ebtesam Al-Ali
Kuwait Institute for Scientific Research, Kuwait
Title: Diagnosis and genetic identification of tomato yellow leaf curl virus (TYLCV) infecting tomato crops in kuwait
Time : 12:15-12:45
Biography:
Ebtesam Al-Ali completed her BSC in 1993 at Kuwait University and worked for Kuwait University as Research Assistant, then joined KISR on October 5, 1993 and led six projects. She has published more than 25 papers in reputed journals and international conferences. She has experience in Plant Virus Detection, Primer Design, Cloning and Sequencing, ELISA, DNA Extraction, PCR Amplification, RCA Rolling Circle Amplification and TYLCV detection on tomatoes. She was trained twice at University of Wisconsin Madison under the supervision of Professor Amy Charkowski as well as Washington State University under supervision of Professor Hanu Pappu.
Abstract:
In Kuwait, high economic losses induced by white fly-transmitted viruses necessitates a rapid action for identification and molecular characterization of the virus species present in Kuwait in order to develop and recommend appropriate control strategies. TYLCV was reported as a major pest of tomato but it was not fully characterized at the molecular level in addition to TYLCV. Tomato leaf samples were collected on monthly bases. Collections were made from greenhouses farms in south (Wafra) and north (Abdally) agricultural district areas in Kuwait. Gemini viral DNA was extracted from 100 collected infected tomato leaf samples using Dellaporta method. Then, PCR protocol was optimized and used on 50 collected infected leaf tomato samples by using two different primer pairs. Field observations carried out in this project for whole growing period of tomato grown under protection indicated that the symptoms such as leaf yellowing, leaf cupping, leaf curling and stunting of plants were common. Whitefly infestation was very common. Data from this activity showed that TY1(+) & TY2(-) primers were successful in detecting the TYLCV, and partially sequencing of the positive TYLCV done and the amplicon showed a new spp. of TYLCV was detected. These data indicate that the TYLCV present in Kuwait belongs to a separate species from those reported in other countries, and hence, has been named tomato yellow leaf curl Kuwait virus (TYLCKWV).
Ahmed EM Azazy
Ain Shams University, Egypt
Title: Association of long noncoding RNA and c-JUN expression in hepatocellular carcinoma patients
Time : 12:45-13:15
Biography:
Ahmed E M Azazy is a fourth year Medical Cadet at Armed Forces College of Medicine (AFCM), active member at International Genetic Engineering Machine (IGEM). He has published three papers in international journals.
Abstract:
Background: Long noncoding RNAs (lncRNAs) have emerged as key elements in modulating gene expression in different biological contexts. Accumulating evidence indicates that lncRNAs are strongly implicated in hepatocellular carcinoma (HCC) development and progression.
Objectives: Long non coding RNA-urothelial cancer associated 1 (lncRNA-UCA1) and cellular jun proto-oncogene (c-JUN) have been scheduled in this study to discuss their possible association in HCC patients based on bioinformatics tools and clinical validation.
Patient & Methods: We used quantitative real-time PCR (QPCR) to evaluate the expression of lncRNA-UCA1 and C-JUN in serum of 70 patients with HCC, 32 patients chronic hepatitis C (CHC) and 38 healthy subjects and their correlation with different clinicopathological factors. The prognostic significance of lncRNA-UCA1 and c-JUN were tested by Kaplan-Meier survival analysis.
Results: The expression of lncRNA-UCA1 and C-JUN was positive in 91.4% HCC patients with strong discriminating power between HCC and healthy subjects and CHC patients as well. The median follow up period was 29 months. The survival analysis showed that both lncRNA-UCA1 and C-JUN were independent prognostic factors. Of note, we identified C-JUN expression changes consistent with the lncRNA-UCA1 target regulation.
Conclusion: Our study sheds light on the possible role of lncRNA-UCA1 and C-JUN mRNA as promising diagnostic and prognostic markers as well as potential therapeutic targets in HCC.
Ruth Navon
Tel-Aviv University, Israel
Title: Effect of cyclic, low dose pyrimethamine treatment in patients with late onset tay sachs: an open label, extended pilot study
Biography:
Ruth Navon is currently working in the 1Tel Aviv University, Israel. Ruth Navon international experience includes various programs, contributions and participation in different countries for diverse fields of study. Ruth Navon research interests reflect wide range of publications in various national and international journals.
Abstract:
Late onset Tay-Sachs disease (LOTS) is a rare neurodegenerative lysosomal storage disease which results from mutations in the gene encoding the a-subunit (HEXA) of beta-hexosaminidase enzyme (HexA). At present, no effective treatment exists for LOTS. Pyrimethamine (PMT) was previously shown to act as a HexA chaperone in human fibroblasts in vitro carrying some (e.g., aG269S), but not all LOTS-related mutations. The present study assessed the effect of cyclic, low dose and long term pyrimethamine treatment on HexA in subjects with LOTS. In an open label trial in 4 LOTS patients, PMT was initiated at an average daily dose of similar to 2.7 mg and administered cyclically guided blood lymphocyte HexA activity for a mean duration of 82.8 (+/- 22.5; SD) weeks. HexA activity rose in all subjects, with a mean peak increase of 2.24 folds (+/- 0.52; SD) over baseline activity was observed. The mean treatment time required to attain this peak was of 15.7 (+/- 4.8; SD) weeks. Following increase in activity, HexA gradually declined with the continued use of PMT, which was then stopped, resulting in the return of HexA activity to baseline. A second cycle of PMT treatment was then initiated, resulting again in an increase in HexA activity. Three of the patients experienced a measurable neuropsychiatric deterioration whereas one subject remained entirely stable. We conclude that cyclic low dose of PMT can increase HexA activity in LOTS patients. However, the observed increase is repeatedly transient and not associated with discernible beneficial neurological or psychiatric effects.
Haesu Ko
National Institute of Animal Science, Korea
Title: Annotation and geneticvariation studyof swine CD(cluster of differentiation) genes
Biography:
Haesu Ko has completed her Bachelor’s degree in 2016 at Chonbuk National University, South Korea and presently, she is pursuing her Master's degree from the same university. She is a Junior Researcher of Animal Genomics & Bioinformatics Division, National Institute of Animal Science, South Korea.
Abstract:
CD (cluster of differentiation) markers are cell surface molecules on immune-related cells such as leucocytes, which have various physiological functions, especially immune responses. CD markers presently range from CD1 to CD371 in human. CD molecules are mostly cell surface proteins encoded by genes. In the case of swine CD genes, it remains less well known by comparison with human CD genes. We defined the structures of the swine CD genes by assembly of transcriptome sequencing data and comparing with multi-species CD genes. Transcriptomic data were produced by RNA sequencing in 15 tissues of pigs in NIAS and obtained from public database such as Ensembl and NCBI. All swine CD genes were annotated on the Korean native pig genome map constructed by de novo assembly. We classified the all annotated swine CD genes by comparing the genomic sequences and finding common motif conserved between them. After annotating swine CD genes, genomic variations were investigated using mapping with paired-end sequencing data of a total of 59 pigs of five breeds. In the study, furthermore, we predicted variant effects on the swine CD genes based on their protein structure-functional relationships. We hope to provide new insights and extend information for understanding of swine immune system based on the genomic variations of the swine CD genes.