2^nd International Conference on Transcriptomics September 12-14, 2016 Philadelphia, Pennsylvania, USA

Chair

Michael Abend

Bundeswehr Institute of Radiobology, Germany

Co-Chair

Lyudmila Gulyaeva

Russia Novosibirsk State University, Russia

Session Introduction

Lyudmila Gulyaeva

Russia Novosibirsk State University, Russia

Title: MicroRNA Expression Profile in Breast Cancer

Time : 11:20: 1 1:50

Biography:

Lyudmila Gulyaeva, PhD, Doctor of Biology is currently a Professor of Molecular Biology and Biochemistry at Novosibirsk State University, Head of the Molecular Carcinogenesis Laboratory of Institute of Molecular Biology and Biophysics, Novosibirsk, Russia. She got her PhD in Biochemistry in 1986 and Doctor Degree in 2000. She has spent most of her scientific carrier studying drug-metabolizing enzymes and their associations with cancer. A special interest of her research is receptor-mediated mechanism of hormone-related cancer and role of microRNA in regulation of target genes. The results of her scientific activity were published in over 180 scientific papers.

Abstract:

MicroRNAs (miRs) play an essential role in epigenetic alterations of gene expression. Dysregulation of microRNAs expression was observed in many types of cancer including breast cancer (BC). We aimed to determine the microRNA expression in breast tumor samples (n=149) with various receptor phenotypes. Bioinformatics analyses with help of the “Pathway Studio” program determined potential microRNAs: miR-21, 221, 200а, 146, 17, 27, 155, 125 and 16, which are significantly correlated with the expression of ER, PR and HER2. Our study has shown that expression of oncogenic miR-21 and miR-221 increased mainly in the triple negative BC (TNBC), whereas miR-200a and miR-146 were highly expressed in the ER-positive BC. The decreased expression of miR-17 was found in TNBC. There was no significant correlation between miR-27,-155 expression and BC phenotypes. For the first time, we have shown that the elevated level of miR-16 expression is correlated with high expression of ER and HER2. The in silico analysis has shown that studied oncogenic miRs can target ERα, PR, CYP19. Moreover, the expression profile of miR-21, 221, 155, 222 and 205 can change under neoadjuvant radio- and chemotherapy of BC patients. To understand the reasons for the changes in the miR profile, we have studied the expression of studied miRs together with miR-326,-3573,-483,-126a,--1843a,-190a,-6327, their “host” genes and target mRNAs, involved in cell proliferation and differentiation in liver, breast, ovaries and uterus of rats treated with DDT and benzo(a)pyrene. Tissue-specific expression of studied miRs was found, that could be explained by the tissue-specific activation of nuclear receptors by xenobiotics. Thus, the results confirmed the role of microRNAs in carcinogenesis of mammary gland that may open new strategies in breast cancer diagnostics and treatment.

Julie Secombe

Einstein College of Medicine, USA

Title: KDM5: More than just a histone demethylase

Time : 11:25: 11:55

Biography:

Julie Secombe received her PhD from the University of Adelaide, Australia, studying the regulation of the cell cycle. Her Pos-tdoctoral training with Dr. Robert Eisenman at the Fred Hutchinson Cancer Center centered on defining the means by which the oncoprotein Myc regulates cell growth. She started her own research group in 2009 at the Albert Einstein College of Medicine. Her research focuses on defining mechanisms of transcriptional regulation, with particular emphasis on two transcriptional regulators, Myc and KDM5/Lid.

Abstract:

Our work focuses on understanding the functions of the transcriptional regulator KDM5. Mammalian cells encode four KDM5 paralogs, KDM5A-D, three of which are clinically important: overexpression of human KDM5A or KDM5B are associated with cancer, and mutations in KDM5A, KDM5B or KDM5C are found in patients with intellectual disability. Yet the basic mechanisms by which this family of proteins functions in a physiological setting remain largely unknown. Taking advantage of the fact that Drosophila encodes a single, essential, KDM5 paralog, we have recently found that KDM5 regulates genes essential to mitochondrial function. This finding is significant because mitochondrial dysfunction is implicated in a large number of human diseases, including cancer and cognitive dysfunction. Importantly, KDM5 regulates mitochondrial function genes independently of its well-described JmjC domain-encoded histone demethylase activity. Instead, KDM5 requires its PHD motif that binds to histone H3 that is di- or trimethylated on lysine 4 (H3K4me2/3). Genome-wide, KDM5 binding overlapped with the active chromatin mark H3K4me3, and a fly strain specifically lacking H3K4me2/3 binding showed defective KDM5 promoter recruitment and gene activation. KDM5 therefore plays a central role in regulating mitochondrial function by utilizing its ability to recognize specific chromatin contexts.

Jianbo Wang

Wuhan University, China

Title: The transcriptomic studies on rice (Oryza sativa) developing embryo and endosperm

Time : 11: 55: 12:25

Biography:

Jianbo Wang has completed his PhD from Wuhan University, China. He is interested in the research on plant reproductive development, and has published more than 40 papers in reputed journals

Abstract:

RNA-seq analysis of rice (Oryza sativa L.ssp. indica cv. 9311) developing embryo (3, 7 and 14 DAP (Days after Pollination)) generated 27,190 genes. Among these genes, the number of genes expressed stage-specifically were 1,131, 1,443 and 1,223 and a total of 1,011 differentially expressed genes were identified, while 672 genes with significant changes in expression between 3 and 7 DAP, 504 DEGs between 7 and 14 DAP. A large number of genes related to metabolism, transcriptional regulation, nucleic acid replication/processing and signal transduction were expressed predominantly in the early and middle stages of embryogenesis. In addition, we found that many transcription factor families may play important roles at different developmental stages, not only in embryo initiation but also in other developmental processes. The endosperm development has an important role for rice yield and quality. We used RNA-seq to reveal the molecular mechanisms involved in rice endosperm development. Three cDNA libraries were taken from rice endosperm at 3, 6 and 10 days after pollination (DAP), which resulted in the detection of 21,596, 20,910 and 19,459 expressed genes, respectively, and 10,371 genes were differentially expressed. A large number of genes related to ribosomes, the spliceosome and oxidative phosphorylation were found to be expressed in the early and middle stages. Plant hormone, galactose metabolism and carbon fixation related genes showed a significant increase in expression at the middle stage, whereas genes for defense against disease or response to stress as well as genes for starch/sucrose metabolism were strongly expressed during the later stages of endosperm development. The RNA-Seq result confirmed the expression characteristics of rice endosperm development.

Lyudmila Gulyaeva

Russia Novosibirsk State University, Russia

Title: Workshop on “Regulation of gene expression by xenobiotics and microRNA”

Time : 12:25-13:25

Biography:

Lyudmila Gulyaeva, PhD, Doctor of Biology is currently a Professor of Molecular Biology and Biochemistry at Novosibirsk State University, Head of the Molecular Carcinogenesis Laboratory of Institute of Molecular Biology and Biophysics, Novosibirsk, Russia. She got her PhD in Biochemistry in 1986 and Doctor Degree in 2000. She has spent most of her scientific carrier studying drug-metabolizing enzymes and their associations with cancer. A special interest of her research is receptor-mediated mechanism of hormone-related cancer and role of microRNA in regulation of target genes. The results of her scientific activity were published in over 180 scientific papers.

Abstract:

Gene expression is regulated by various mechanisms at transcriptional and post-transcriptional levels. Transcriptional mechanisms involve activation of transcription factors upon ligand binding or activation of signal transduction pathways. Many foreign compounds can bind specific nuclear receptors (AhR, CAR, PXR, PPARs) leading to activation of expression of target genes.  Toxicity of chemicals is dependent on specific signaling pathway that involves chemical activates. Such factors as structure of chemicals, gender and species of studied animals determine the degree and kind of toxic effects of the compound. We have investigated species-specific effect of phenobarbital and different chemical modification of 2,4,6-tryphenyldioxane-1,3 (TPD) on the cytochrome P450 (CYP) – key enzyme in xenobiotic metabolism. Selective effects of closely resembling compounds on CYP2B induction on transcriptional level have been uncovered with the help of Enzyme activity assays, Western-blot, gel shift analysis and RT-qPCR. Additionally, microRNAs play important role in post-transcriptional regulation of numerous genes, in particular of the cytochrome P450. The effects caused by xenobiotics can be attributed to changes in the miRNA expression profile, thus leading to changes in gene regulation. This can explain the detrimental effects that these chemicals have on human health. We used in silico methods and experimental approaches in order to investigate whether some xenobiotics like DDT and benzo(a)pyrene affect the expression of miRNAs through the activation of nuclear receptors (NRs): CAR (DDT) and AhR (BP), as well as estrogen receptor ER1 and ER2. The study showed that expression of microRNAs might vary under xenobiotic induction through NRs activation. This effect depends on the tissue type of experimental animals. The correlation between expression of microRNAs, host genes and target genes was shown. Thus, xenobiotics can dramatically change both protein coding genes and microRNA expression profile, greatly contributing to their toxic effects including carcinogenesis.

Break: Lunch 13:25-14:25 @ Benjamin’s Restaurant

Yongyan Sun

Chinese Academy of Sciences, China

Title: Application of Transcriptomics on study of biological effects of magnetic field exposure

Time : 14:25:15:05

Biography:

Yongyan Sun is now a PhD candidate in Institute of Urban Environment, Chinese Academy of Sciences.

Abstract:

Transcriptomics is one of functional genomic approaches widely applied in life science research in recent years. Based on the background of crosses and integration between environmental science and life science subjects, growing cutting-edged molecular technologies such as proteomics, metabolomics and etc., are applied in studying environmental problems, especially exploring biological relationships between human living environments and health. Electromagnetic environment is one of extensively existed urban environmental factors in modern life during the development of urbanization and modernization. Thus, it is indispensable and inevitable to investigate the biological effects of electromagnetic field (EMF) on human health and disease. Transcriptomic analysis, which could to some extent reflect the gene expression alteration under EMF exposure, is rewarding to much deeper understanding on molecular mechanism of living organism sensing and responsing to EMF exposure. In our study, we have explored the bio-effects of extremely low-frequency electromagnetic field (ELF-EMF) and radio frequency electromagnetic field (RF-EMF) via transcriptomic analysis on model organism, such as Saccharomyces cerevisiae, Drosophila melanogaster and Caenorhabditis elegans. Several results indicate that the living organism indeed response to EMF exposure and different model organism showed changes in various ways. Therefore, the utilization of transcriptomic approach on studying the health effect of EMF exposure lays the molecular basis for further research on mechanism of electromagnetic field sensing and responsing.

Erin E Sparks

Duke University, USA

Title: Exploring underground networks: the transcriptional control of plant root development

Time : 15:05:15:35

Biography:

Erin E Sparks received her PhD in 2011 from Vanderbilt University and is currently a Post-doctoral Associate with Philip Benfey at Duke University. She has a longstanding interest in the molecular development of branched organs.

Abstract:

Tissue-specific gene expression is often thought to arise from spatially restricted transcriptional cascades. However it is unclear how expression is established at the top of these cascades. The SHORTROOT-SCARECROW transcriptional cascade is central to cell fate decisions in the Arabidopsis root cortex and endodermis (ground tissue). We experimentally derived a gene regulatory network for transcription factors in the Arabidopsis root ground tissue by enhanced yeast-1-hybrid assays. We then used this ground tissue gene regulatory network to dissect the regulation of the SHORTROOT-SCARECROW transcriptional cascade. We validated network predictions in planta and identified regulators of SCARECROW and SHORTROOT expression. Our results suggest that there is intercellular coordination of SHORTROOT and SCARECROW expression. Further, we leveraged cell type specific transcriptome data within a logistic regression to develop a model in which expression at the top of this transcriptional cascade is established through the opposing gradients of activators and repressors.

 

Bao Liu

3rd Military Medical University, China

Title: Inflammatory response in the pathogenesis of acute mountain sickness revealed by transcriptome analysis

Time : 15:35:16:05

Biography:

Bao Liu is an undergraduate student at 3^rd Medical University, Chongqing, China. He is studying the molecular mechanisms of high altitude illness using transcriptome.

 

Abstract:

Acute mountain sickness (AMS) is a common disabling condition in individuals experiencing high altitudes, which may progress to life-threatening high altitude cerebral edema. To gain further insight into the molecular underpinnings that participated in the pathophysiology of AMS. We studied paired whole blood transcriptomes from 10 individuals, 5 AMS and 5 non-AMS diagnosed by Lake Louise scoring system, comparing post-exposure to high altitude (5300 m) transcriptomes to their pre-exposure counterparts. We identified 1,164 and 1,322 differentially expressed transcripts in participants with AMS and non-AMS, respectively. Among these genes, only 328 transcripts were common in both AMS and non-AMS individuals. Moreover, immune and inflammatory responses were more enriched in participants with AMS, but not in non-AMS individuals. This study identifies that inflammatory response induced by hypoxia, may be critical in AMS pathogenesis, which is a new direction for AMS pathogenesis investigation and useful for developing pharmacological prophylaxis and treatment.

Break: Refreshment 16:05-16:30 @ Foyer

Chair

Henry M Sobell

University of Rochester, USA

Co-Chair

Andrew Grimson

Cornell University, USA

Session Introduction

Andrew Grimson

Cornell University, USA

Title: Mining transcriptome data to identify consequential microRNAs and their targets

Time : 12:30 : 13:00

Biography:

Andrew Grimson has completed his PhD at the University of Wisconsin-Madison in 2004, investigating mRNA decay. He completed his Post-doctoral fellowship in 2009, mentored by Dr. David Bartel (Whitehead Institute/MIT), investigating microRNAs and their targets. Currently, he is an Assistant Professor of Molecular Biology and Genetics at Cornell University. His lab work is on post-transcriptional regulation, in particular the role of the 3′ untranslated region (3′UTR); research is focused upon the basic science of 3′UTRs, together with biological processes under post-transcriptional control. His research is supported by grants from the NIH, and by a Research Scholar Grant from the American Cancer Society.

Abstract:

Although microRNAs (miRNAs) contribute to essentially all mammalian gene regulatory pathways, the identification of consequential miRNAs active in a given cell-type remains challenging. To address this challenge, mRNA and miRNA transcriptome profiles can be used to infer the identities of miRNAs with regulatory impacts. We used such approaches to discover miRNAs that might underlie age-dependent differences in CD8+ T cells, which protect organisms from intracellular diseases. In early life, mice and other mammals are deficient at generating memory CD8+ T cells, which protect from re-infection; we hypothesized that age-specific activity of one or more miRNAs underlie these differences. We profiled mouse transcriptomes from CD8+ T cells at different stages of infection, comparing adult and neonatal profiles. Adult and neonatal miRNA profiles were surprisingly similar in effector cell populations created during infection; however, we observed large differences prior to infection; in particular, miR-29 and miR-130 exhibit significant differential expression between adult and neonatal naive cells. Importantly, we detected reciprocal changes in expression of mRNA targets for both miRNAs; moreover, targets include Eomes and Tbx21, key genes that regulate memory CD8+ T cell formation. In addition, the mRNA profiles of neonatal naive cells already resemble those of effector cells. Changes in miR-29 and miR-130 and their targets are conserved in human CD8+ T cells, and in other T cell lineages. Together, these results suggest that miR-29 and miR-130 are important regulators of memory CD8+ T cell formation, and that neonatal cells are committed to a short-lived effector cell fate prior to infection.

Michael Abend

Bundeswehr Institute of Radiobology, Germany

Title: Association of radiation-induced genes with non-cancer chronic diseases in Mayak workers occupationally exposed to prolonged radiation

Time : 13:00 : 13:30

Biography:

Michael Abend studied Human Medicine at the University Cologne and finished his medical examination for a Doctor degree (medicine) during the same time. He earned a Professorship for Radiobiology at the Technical University, Munich, Germany and a Master’s degree in Epidemiology from Institute for Biometry, Epidemiology and Informatics at the Clinics of the Gutenberg University, Mainz, Germany. He worked at different scientific institutions outside Germany (e.g. Radiation Epidemiology Branch, DCEG, Bethesda, USA). He is currently the Deputy Director of the Bundeswehr Institute of Radiobiology and published almost 100 papers in reputed journals.

Abstract:

We examined the association of gene expression with non-cancer chronic disease outcomes in Mayak nuclear weapons plant workers who were exposed to radiation due to their occupation. We conducted a cross-sectional study with selection based on exposure status (either combined incorporated 239Pu or external gamma-ray [n=82], or external gamma-ray exposure only [n=18]) of Mayak plant workers living in Ozyorsk who were alive in 2011; and an unexposed comparison group (n=50) of Ozyorsk residents. Peripheral blood was taken and RNA was isolated, converted into cDNA and stored at -20°C. In a previous analysis, we screened the whole genome for radiation-associated candidate genes and validated 15 mRNAs and 15 microRNAs using qRT-PCR. Within the present analysis, we examined the association of these genes with 15 different chronic diseases on 92 samples (47 males, 45 females). We examined the radiation to gene and gene to disease associations in statistical models stratified by gender and separately for each disease and exposure. Unconditional logistic regression was used for genes that were significantly associated with radiation exposure and a specific disease outcome. Altogether 12 mRNAs and 9 microRNAs appeared to be significantly associated with 6 diseases, e.g. atherosclerotic diseases (4 genes, OR: 2.5-10, concordance: 70-75%), systolic blood pressure (6 genes, OR: 3.7-10.6, concordance: 81-88%) and body mass index (1 gene [miR-484], OR: 3.7, concordance: 81%). All associations were gender and exposure dependent. Hence, gene expression changes observed after occupational prolonged radiation exposures seem to increase the risk for certain non-cancer chronic diseases.

Break: Lunch 13:30-14:30 @ Benjamin’s Restaurant

Arindam Basu

Penn State University, USA

Title: YY1 controls long range DNA interactions of Ig heavy chain locus during class-switch recombination

Time : 14:30: 15:00

Biography:

Arindam Basu has completed his PhD from Indian Institute of Science (IISc), Bangalore in India and continued his Post-doctoral research on gene expression and regulation in the laboratory of Dr. Michael L. Atchison at the University of Pennsylvania. He is currently an Assistant Professor at Penn State University, Brandywine campus where he teaches undergraduate courses. His primary research interests have been in the area of epigenetic regulation by Polycomb group of proteins and long-range DNA interactions. He has published several papers demonstrating the role of Polycomb proteins in chromatin organization.

Abstract:

B lymphocyte development involves a temporal order of long-range DNA recombination events that results in the assembly of variable (V), diversity (D) and joining (J) gene segments to produce functional Ig genes. In activated splenic B cells and germinal center cells, somatic hypermutation and class switch recombination (CSR) regulate IgH expression. The rearrangement of distal V genes requires locus contraction and DNA looping and studies showed that YY1^-/- pro-B cells have greatly impaired distal VH gene rearrangement and IgH locus compaction. Studies have shown that YY1 is essential for B cell development and we have shown that numerous long range DNA loops are also required for CSR and loss of YY1 significantly reduces CSR. CSR involves DNA looping between the intronic enhancer (Eµ) and the 3’RR enhancer. This Eµ - 3’RR synapse is dependent on YY1 as measured by 3C and 3D-FISH assays, as well as by ChIP-seq. We performed ChIP-seq with splenic B cells to investigate whether YY1 colocalizes with condensins, cohesins and PcG proteins to understand the mechanism of YY1 mediated locus contraction. The raw sequences were analyzed using bowtie2.  The Homer software package was used to analyze the aligned reads for regions of over representation of read depth (peaks) utilizing the find Peaks factor program and statistical significance was determined by using a FDR of 1%, 4-fold reads in peak over background, and requiring a cumulative poisson p-value of 0.0001. Our data indicated that SMC4, Rad21 and EZH2 bind at the 3’RR hs4 site along with YY1.

Alqaisi K M

University of Otago, New Zealand

Title: The application of transcriptome sequencing: New insights into the understanding of sex-steroid hormone synthesis in echinoderms

Time : 15:00: 15:30

Biography:

Alqaisi K M has completed his PhD in 2014 from the Department of Zoology at University of Otago, New Zealand. His PhD research was focused on understanding vitellogenesis and sex steroid hormone synthesis in Echinoderms using advance molecular and biochemical techniques. He also has research experience in the area of developmental neurotoxicity from his Master’s research. He has published several papers in peer-reviewed journals. Currently, he is interested in understanding the endogenous signals that control gametogenesis in Echinoderms. Also, he is interested in studying how brain signals control energy homeostasis and obesity in human.

Abstract:

In invertebrates, the presence of sex steroid hormones such as progesterone (P4), testosterone (T) and estradiol-17β (E2) has been reported in Echinoderms and Molluscs and classified as vertebrate-like sex steroid hormones (VLSHs). In Echinoderms, VLSHs levels were found to change in relation to gametogenesis and suggested to be synthesized primarily in the ovary. However, the synthesis and functions of these VLSHs in Echinoderms are still poorly understood. Therefore, this study aimed to identify transcripts of enzymes that are crucial in the steroid biosynthetic pathway by selecting ovaries from the sea star Patiriella regularis in early and late stages of oogenesis for de novo transcriptome sequencing using Illumina HiSeq2000. The study also investigated the steroidogenic activity of P. regularis ovary and pyloric caeca during the reproductive cycle by incubating these tissues with pregnenolone (P5) or androstenedione (AD) and measuring P4, AD, T and E2 concentrations using liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. Surprisingly, the transcripts that encode key steroidogenic enzymes, such as P450scc, 3β-HSD and aromatase, were not found in the transcriptome from the ovary. The results also showed the ability of both pyloric caeca and ovary to convert P5 into P4 and AD into T, but the in vitro production of P4 or T was not significant during the reproductive cycle. Therefore, it seems probable that the synthesis of VLSHs in P. regularis stems from non-specific activity of hydroxysteroid dehydrogenases and P450 enzymes. More similar studies using advanced molecular techniques are needed to understand the synthesis and function of VLSHs in invertebrates.

Nina B Fedorova

Institute of Cytology and Genetics, Russia

Title: Transcriptomics: Genes and ontogenes in Drosophila

Time : 15:30: 16:00

Biography:

Nina B Fedorova has completed her graduation from Tomsk State University, The Biology Faculty. In 2002, she finished her Post-graduate studies at Institute of Cytology and Genetics in Novosibirsk. She received her PhD in Genetics in 2007. She is a Researcher in the Laboratory of Mechanisms of Cell Division of the Institute and has published more than 20 papers in reputed Russian and foreign journals. Her research interest is in the relationship between facts and concepts of classical genetics and modern investigations in epigenetics, molecular and cellular biology.

Abstract:

For the existence of genetic systems, independent hereditary factors are not sufficient, such as Mendelian genes. The search for the hereditary factors of a different type was held. A new class of mutations, called conditional, was isolated In D. melanogaster. In a restrictive genotype, mutant dies and permissive survives and reproduces. Besides their conditional nature, mutations in the permissive genotype display a set of specific features that drastically distinguish them from conventional mutations. They are: 1) dominant; 2) as a rule, lethal; 3) drastically decrease fertility; 4) interact with chromosome rearrangements; 5) switch the genome from a stable to an unstable state; 6) increase basal metabolism; 7) induce modifications and morphoses; and 8) their manifestation is inherited in a parental manner. Four properties of the mutations - conditional manifestation and 1), 4) and 8) allow asserting that the mutated genes are: (1) segments of DNA; (2) their products are duplexes of RNA (3) active in germ cells and (4) repeated in the genome. The formation of morphoses in mutants suggests that the genes control the ontogeny (called ontogenes). Thus the genetic system comprises the genes working on the script DNA-RNA-protein and ontogenes working on the script of DNA-RNA. First engaged in the production of the "building material" in the organism, the second controlled this process and maintained the functioning of the organism. Such different functions of the genes depend on the type of transcript formed by the DNA, time and place of its origin.

 

Break: Refreshment 16:00-16:15 @ Foyer

Juan Antonio Valdés

Universidad Andrés Bello, Chile

Title: RNA-seq analysis reveals significant transcriptome changes in the fine flounder (Paralichthys adspersus) and the red cusk-eel (Genypterus chilensis) under stress

Time : 16: 15: 16: 45

Biography:

Juan Antonio Valdés is working as an Associate Professor of the Faculty of Biological Sciences at the Andres Bello University, Chile and Associate Researcher of the Interdisciplinary Center for Aquaculture Research (INCAR), where he leads the Molecular Biotechnology laboratory. His research is focused on the understanding the molecular mechanisms regulating skeletal muscle growth in teleost. The application of this expertise has provided new insights in the field of stress response in marine fishes. Currently, he is focusing on the identification and characterization of cortisol-mediated non-genomic signaling in the stress response of salmonids, by using next-generation transcriptomic and proteomic tools.

Abstract:

In the last years next generation sequencing technologies (NGS) and RNA-seq have revolutionized the fields of transcriptomics, providing the possibility to investigate gene expression and pathways involved in countless biological processes of non-model aquatic animals. In recent years, there is a trend towards diversifying breeding species to maintain the sustainability of the global aquaculture industry. Among the cultivated marine species are the red cusk-eel (Genypterus chilensis) and fine flounder (Paralichthys adspersus). These marine fishes are highly valued in national and international markets due to exceptional flesh quality and high nutritional value. However, these species in captivity are susceptible to stress, showing low growth and high mortality rates, which could be due to alteration in the compensatory response to stress. In this work, we studied the effect of handling stress (acute stress) and high density stress (chronic stress) on the metabolic and growth response of G. chilensis and P. adspersus. Using Illumina RNA-seq technology, skeletal muscle and liver transcriptomes were analyzed, revealing a significant up-regulation of genes associated with liver angiogenesis and skeletal muscle atrophy under stress. Conversely, the down-regulated genes were associated with liver steatosis and skeletal muscle contraction. This work will not only allow consolidating the red cusk-eel and fine flounder’s commercial cultivation but also lay the foundation of marine aquaculture industry having a significant impact on national economic development.

 

Rakesh Kumar

George Washington University, USA

Title: Breast cancer transcriptome: From triple negative breast cancer to HER2-overexpressing isogenic TNBC Cells

Time : 16:45: 17:15

Biography:

Rakesh Kumar is an internationally recognized Cancer Biologist with a particular focus on breast cancer. His research interests are focused on the mechanisms of cancer progression with special emphasis on chromatin and cytoskeleton remodeling, and targeted cancer therapeutics. He has received several awards and honors for his research work since 1995. He has authored over 220 original research papers, 67 reviews, 10 book chapters and edited 6 books/volumes in the area of cancer research. He has trained over 65 fellows and students, and shared his knowledge by delivering over 220 invited, keynote or plenary lectures at academic institutions, universities and scientific meetings

Abstract:

In recent years, Kumar’s lab used high-throughput whole genome sequencing to gain a deeper genomic insight of the triple-negative breast cancer (TNBC), estrogen receptor positive and HER2 positive breast cancers, and revealed new regulatory intricacies and pathways in breast cancer. These results re-validated an expected inter- and intra-tumor genomic heterogeneity due to differential expression of transcripts and splicing and promoter switching. To address the issue of clonal origin of breast cancer, the laboratory also generated isogenic TNBC breast cancer clones stably expressing HER2 as a part of a master dissertation project, and identified HER2-modulated genes through microarray analysis. The laboratory continued with this theme as a part of a doctoral dissertation project and subjected these isogenic clones to RNA-sequencing analysis in the context of HER2-transcriptome. This phase of the work was centered on identifying differential expressed genes and alternative spliced transcripts, transcription and splicing factors modulated by HER2 as an attempt to explain the basis of the noted differential expression in isogenic clones.

An Yuan Guo

Huazhong University of Science and Technology, China

Title: Regulatory network analysis reveals miR-146b-5p within BCR-ABL1–positive microvesicles promotes leukemic transformation of hematopoietic cells

Time : 17:15: 17:45

Biography:

An Yuan Guo has completed his PhD from Peking University and Post-doctoral studies from VCU and Vanderbilt University. His research focuses on the transcription factor and ncRNA regulatory network in complex diseases with NGS data and bioinformatics database construction. He is an expert in bioinformatics database and developed a serial of databases (AnimalTFDB, miRNASNP and lncRNASNP). He developed an approach to study the microRNA and TF co-regulatory network in complex diseases. He has published about 50 papers in Molecular Psychiatry, Cancer Research, NAR, Bioinformatics, Briefings in Bioinformatics, Human Mutation etc and served as an Editor of Scientific Reports.

Abstract:

Evidence is accumulating that extracellular microvesicles (MV) facilitate progression and relapse in cancer. Using a model in which MVs derived from K562 chronic myelogenous leukemia (CML) cells transform normal hematopoietic transplants into leukemia-like cells, we defined the underlying mechanisms of this process through gene-expression studies and network analyses of transcription factors (TF) and miRNAs. We found that antitumor miRNAs were increased and several defense pathways were initiated during the early phases of oncogenic transformation. Later, oncomiRs and genes involved in cell cycle, DNA repair and energy metabolism pathways were upregulated. Regulatory network analyses revealed that a number of TFs and miRNAs were responsible for the pathway dysregulation and the oncogenic transformation. In particular, we found that miR-146b-5p, which was highly expressed in MVs, coordinated the regulation of cancer-related genes to promote cell-transforming processes. Notably, treatment of recipient cells with MV derived from K562 cells expressing mimics of miR-146b-5p revealed that it accelerated the transformation process in large part by silencing the tumor-suppressor NUMB. High levels of miR-146b-5p also enhanced reactive oxygen species levels and genome instability of recipient cells. Taken together, our findings showed how upregulation of oncogenic miRNAs in MVs promote hematopoetic cells to a leukemic state, as well as a demonstration for TF and miRNA coregulatory analysis in exploring the dysregulation of cancers and discovering key factors.

 

Byung Wook Yun

Kyungpook National University, South Korea

Title: Drought stress-mediated transcriptome profile reveals NCED as a key player modulating drought tolerance in different cultivars of P. davidiana (Korean Aspen)

Time : 17:45: 18:15

Biography:

Byung-Wook Yun has completed his PhD jointly at Kyungpook National University (KNU) and Korea Research Institute of Bioscience & Biotechnology (KRIBB) in 1998, investigating the function of plant peroxidases. He completed his Post-doctoral and senior research fellowship at the University of Edinburgh (UK), studying Nitric Oxide (NO) signaling in plant immune system, mentored by Professor Gary Loake. Currently he is working as an Associate Professor of the School of Applied Biosciences at KNU. His Plant Functional Genomics Lab is focusing on NO-mediated plant defense system toward both biotic and abiotic stresses using transcriptomics approaches.

Abstract:

Forest trees, including poplar, have evolved to overcome harsh environmental conditions including drought stress. Populus trichocarpa has been studied as a model poplar species through biomolecular approaches and is the first tree species to be genome sequenced. In contrast, the genome of P. davidiana, the Korean aspen, has not been sequenced and is considered highly tolerant to drought stress. In this study, we used high throughput RNA-Seq mediated leaf transcriptome analysis to investigate the response of 4 different P. davidiana cultivars to drought stress. Based upon preliminary studies including H₂O₂ measurements and histological staining, the cultivars were divided into two major groups “drought-tolerant (Seogwang9, Palgong2)” and “drought-susceptible (Palgong1, Junguk6-2)”. P. davidiana plants grown on MS (Murashige and Skoog) media for 8 weeks were air-dried for 10 minutes and leaves were harvested for transcriptome analysis along with untreated control samples. Following RNA-Seq, we compared the transcriptome profiles between the two groups for DEGs (Differentially Expressed Gene), GO (Gene Ontology) enrichment analysis, and identified common drought stress marker genes. Further analysis identified two distinct DEGs with contrasting expression patterns in the drought-sensitive and tolerant groups i.e. up-regulated in the drought-tolerant group while down-regulated in the sensitive group. BLAST analysis showed that both these genes encode 9-cis-epoxycarotenoid dioxygenase (NCED), a key enzyme required for ABA biosynthesis. This suggests a significant role of these two genes in conferring drought tolerance to P. davidiana cultivars in the drought-tolerant group. This study presents the first evidence of a significant role of NCED genes in regulating ABA-dependent drought stress responses in P. davidiana as it has already been shown that NCED regulate ABA-dependent drought adaptation via mRNA de-capping machinery in certain varieties of some plant species. We therefore, suggest the utility of these genes as genetic markers for differentiating drought tolerant and sensitive poplar cultivars.