Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 8th World Congress on Molecular Pathology HILTON SAN DIEGO MISSION VALLEY, San Diego, USA.

Day 1 :

  • Day 01

Session Introduction

Dale D Tang

Albany Medical College, New York

Title: Polo-like Kinase 1 (Plk1) in Smooth Muscle and Allergic Asthma
Speaker
Biography:

Dale D. Tang has received training at the University of Texas Southwestern Medical Center at Dallas in 1990s. He is a professor of the Department of Molecular and Cellular Physiology at Albany Medical College, New York, USA. He is Director of Cytoskeletal Signaling and Asthma Research Program at the school. He is an associate editor of BMC Respiratory Research and a member of the Editorial Board of Nature Scientific Reports. His research focuses on the role and mechanism of cytoskeleton-associated proteins in smooth muscle in vitro and the pathogenesis of asthma and hypertension in vivo. He has published >70 peer-reviewed articles in journals including the Journal of Biological Chemistry and Circulation Research.

Abstract:

Smooth muscle contraction and cell proliferation are critical for the pathogenesis of airway hyperresponsiveness and hyperplasia of allergic asthma. Polo-like kinase 1 (Plk1) is a serine/threonine protein kinase that has been implicated in mitosis and cytokinesis. The role of Plk1 in smooth muscle contraction and cell growth has not been previously investigated. Here, stimulation with acetylcholine induces Plk1 phosphorylation at Thr-210 (an indication of Plk1 activation) in smooth muscle. Contractile stimulation also activates Plk1 in live smooth muscle cells as evidenced by changes in fluorescence resonance energy transfer signal of a Plk1 sensor. Plk1 is necessary for smooth muscle force development. Plk1 regulates airway smooth muscle contraction by affecting vimentin phosphorylation at Ser-56, but without modulating myosin light chain phosphorylation. Plk1 phosphorylation is mediated by Ste20-like kinase (SLK), a serine/threonine protein kinase that has been implicated in spindle orientation and microtubule organization during mitosis. Moreover, Plk1 is indispensable for airway smooth muscle cell proliferation. Plk1 knockdown by lentivirus-mediated shRNA attenuates the growth factor-induced phosphorylation of MEK1/2 and ERK1/2. However, Plk1 knockdown does not affect the phosphorylation of Raf-1 or AKT. Finally, smooth muscle conditional knockout of Plk1 attenuates airway resistance, airway smooth muscle hyperreactivity and hyperplasia in a murine model of allergic asthma. Taken together, these findings suggest that Plk1 is critical for the regulation of smooth muscle contraction and cell proliferation. Plk1 regulates smooth muscle contraction by controlling vimentin phosphorylation whereas it orchestrates cell proliferation by modulating the MAPK pathway. Plk1 contributes to the pathogenesis of allergic asthma. Plk1 may be a pharmacological target for the development of new therapy to treat asthma.

(Supported by NIH grants HL-110951, HL-113208 and HL-130340)

Speaker
Biography:

Robert H Schiestl has obtained his PhD from the University of Vienna at the age of 23 years. He was postdoctoral fellow at Edmonton, Alberta, Rochester, NY, and Chapel Hill, NC before being professor at Harvard at the age of 31 where he stayed for 10 years. It’s been 16 years; he is working as a professor at UCLA with 200 publications, 11 patents and 5 startup companies.

Abstract:

Intestinal microbiota plays a role in the nutrient metabolism, modulation of the immune system, arthritis, obesity and intestinal inflammation. In the literature there have been huge differences in the same Atm deficient mice in different labs reported. When our lab moved from Harvard to UCLA we found a similar difference in genetic instability and logevity. When we changed the intestinal microbiota back to conventional microbiota we could reproduce the phenotype at Harvard. We tested Atm deficient mice for genotoxicity, genetic instability, DNA damage, inflammation markers, cancer latency and longevity and high throughput sequencing of the intestinal microbiota. Isogenic mice from different housing facilities showed a four fold difference in life expectancy, a 4.5 fold difference in genetic instability and DNA damage. The onset of lymphomas was significantly 2 fold different. We sequenced the microbiota of both facilities and found Lactobacillus johnsonii 456 as dominant bacterial strain in the health beneficial microbiota. Just this bacterium by itself reduced genotoxicity, reduced inflammation and reduced levels of cytotoxic T cells in the liver and blood.  We also found similar differences in Trp53 deficient and even in wildtype mice. The underlying mechanisms is probably due to inflammation promotion or suppression mediated by the intestinal microbiota. The understanding of this effect may lead to a breakthrough in the understanding of the causes of carcinogenesis, which might lead to prevention of AT, a currently incurable progressive disease and possibly other cancer-prone DNA repair deficient diseases or even wild type mice and people.

Speaker
Biography:

Yaping Tian, Professor of Department of Clinical Biochemistry, Chinese PLA General Hospital and Military Medical School, Professor of Nankai University, Professor of Tsinghua University. Dr Tian received his Master Degree in Medicine from Chinese PLA Postgraduate Medical School in 1989 and PhD from Academy of Military Medical Sciences in 1993. He had been trained as Postdoctoral Fellow for 2 years(1995-1997) in The Queen Elizabeth Hospital, Australia. Dr. Tian has been focusing on the study of the specific serum proteomic profiles and genetic signatures in different diseases, especially on cancer and cardiovascular diseases. He also focused on the studies of antioxidants in herbal medicine and free radical biology. Dr. Tian has received more than 20 grants and published more than 300 scientific papers in peer-reviewed journals. He is on the editorial boards of several journals and the honor chairman of the Clinical Biochemistry and Applied Molecular Biology Association, CSBMB.

Abstract:

Circulating miRNAs (microRNAs) are emerging as promising biomarkers for several pathological conditions, and the aim of this study was to investigate the feasibility of using serum miRNAs as biomarkers for liver pathologies. Real-time qPCR (quantitative PCR)-based TaqMan MicroRNA arrays were first employed to profile miRNAs in serum pools from patients with HCC (hepatocellular carcinoma) or LC (liver cirrhosis) and from healthy controls. Five miRNAs (i.e. miR-885-5p, miR-574-3p, miR-224, miR-215 and miR-146a) that were up-regulated in the HCC and LC serum pools were selected and further quantified using real-time qPCR in patients with HCC, LC, CHB (chronic hepatitis B) or GC (gastric cancer) and in normal controls. And then the miR-885-5p in HCC metastasis have been studied. The results demonstrated that the expression of miR-885-5p negatively correlated with the invasive and metastatic capabilities of human HCC tissue samples and cell lines. Overexpression of miR-885-5p decreased metastasis of HCC cells in vitro and in vivo. Inhibition of miR-885-5p improved proliferation of non-metastatic HCC cells. Furthermore, we disclosed that miR-885-5p targeted gene encoding β-catenin CTNNB1, leading to decreased activity of the Wnt/β-catenin signaling pathway. The present study indicates that miR-885-5p suppresses the metastasis of HCC and inhibits Wnt/β-catenin signaling pathway by its CTNNB1 target, which suggests that miR-885-5p to be a promising negative regulator of HCC progression and as a novel therapeutic agent to treat HCC.

Kunlun He

Chinese PLA General Hospital, China

Title: Mutation in APOA5 gene associated with hypertriglyceridemia
Speaker
Biography:

Kunlun He has completed his Medical School degree at the age of 21 years from The Third Military Medical University, PhD at the age of 35 years from Chinese PLA Medical School, and postdoctoral studies at the age of 39 years from College of Physicians and Surgeons of Columbia University. He is the vice president of Chinese PLA General Hospital, and the professor of Department of Cardiology. In recent years, he focuses on Translational Medicine of Cardiovascular disease. He has published more than 158 peer reviewed papers, achieved the first class awards of Beijing Science and Technology, and also has been serving as three editorial board members of medical journals.

Abstract:

It is well accepted that the serum lipid level is modulated by genetic and environmental factors. Therefore, identification of the genetic variations involved in lipid metabolism could provide a clue to search for novel pathway in lipid regulation and thereby new therapeutic or preventive methods for coronary artery disease, and further improve the prognosis of heart failure and other cardiovascular disease. We extensively resequenced of our candidate genes and evaluated of rare variant accumulation to identify additional genetic variation responsible for increasing susceptibility to human hyperlipidemia. This study included 638 Chinese patients who were admitted to the Department of Cardiology, Chinese PLA General Hospital (Beijing, China) with chronic heart failure between January 2011 and January 2013. In total, 392 adult patients with hyperlipidemia and 246 population-based controls without hyperlipidemia were included in this study. In order to make the best possible to identify putatively damaging SNVs, five protein prediction algorithms (LRT score, MutationTaster, PolyPhen-2 HumDiv, PolyPhen-2HumVar and SIFT) were applied in non-synonymous SNVs. To explore the potential biological effects of the associated SNPs, we tested whether they were overlapped or correlated with the expression quantitative trait locus from four databases in peripheral blood cells. To mine the potential epistasis effects of the associated SNPs, we exhaustive search all pairs among the variants. This high depth of resequencing study based on target genes repeatedly verified of two common mutation in APOA5 gene associated with hypertriglyceridemia(11-116661392,11-116662579). Besides, 3 rare variants in APOA5 were also found to be related with the increase of triglycerides level. We detect the interaction effect across all pathways and discovered a stronger epistasis effect between gene CNDP1 and APOA5 which both of them came from metabolic process and explained 7.55% genetic variance. We found common and rare variants associated with high triglyceride levels through the high depth of resequencing strategy. More stronger associated signals are needed to excavate with large sample size and multicenter studies. Meanwhile, we also need studies of muti-omics to detect pathogenic mechanism of pathogenic variants.

Speaker
Biography:

Dipak Ramji received his BSc (Hons) degree (Biochemistry) and his PhD from University of Leeds. This was followed by post-doctoral research at the EMBL (Heidelberg) and IRBM (Rome) with fellowships from the Royal Society and the EU. He joined Cardiff University in 1992 and is currently a Reader at Cardiff School of Biosciences. His research is focused on understanding how the immune and inflammatory responses regulate macrophage processes in atherosclerosis with the goal of attaining deeper mechanistic insight and identifying preventative/therapeutic agents. He has published over 80 peer-reviewed papers, reviews and book chapters (h-index = 30; i10-index = 57). He is an Editorial Board member of 16 international journals.

Abstract:

Atherosclerosis, the underlying cause of heart attack and stroke, is an inflammatory disorder of the vasculature regulated by both the innate and adaptive immune systems. Cytokines play a pivotal role in controlling the inflammatory response in atherosclerosis and regulate all the different stages in disease progression.Current approaches to target pro-inflammatory cytokines include neutralization using blocking antibodies or soluble decoy receptors and the use of specific inhibitors against key components of intracellular signaling pathways. In contrast, approaches for anti-atherogenic cytokines include their local delivery and the use of agents that augment their expression/actions. Numerous cytokines are expressed in atherosclerotic lesions and it is therefore essential that their actions in disease progression are fully understood to validate their therapeutic potential and to identify potentially new targets or approaches for therapeutic intervention.

My laboratory has recently been investigating cytokine signaling in atherosclerosis, particularly in macrophagesthat play key roles in all stages of disease progression, using a combination of in vitro and in vivo approaches. Novel insights have been obtained on the actions ofthe cytokines interferon-gamma, transforming growth factor-beta, interleukin-33 and tumour necrosis factor-like protein 1A on key macrophage processes in atherosclerosis (e.g. foam cell formation, regulation of inflammation). For example, we have identified a key role for extracellular signal-regulated kinase: signal transducer and activator of transcription-1 serine 727 phosphorylation axis in the control of macrophage foam cell formation and the regulation of pro-inflammatory gene expression by interferon-gamma. The outcome of our studies on different cytokines will be presented in the context of current therapies and future developments in this field.

Speaker
Biography:

Will be updated shortly

Abstract:

False negative results from archived patient samples are very common in clinical research due to inappropriate tissue handling and aged samples. Standardized collection procedures are very important. Using highly sensitive IHC methods is another way to increase positivity in clinical research. Our studies demonstrate that new TSA methods provide more accurate clinical results.

Speaker
Biography:

Cheng is an attending Hematopathologist at UCMC. He obtained his MD and Master in China. He received his PhD from the University of North Carolina-Chapel Hill. He conducted the first genome-wide epigenetic profiling of DNA and histone (H3K27) methylations in MDS, which led to his winning the Pathologist-in-Training Award from the Society for Hematopathology and the Paul E Strandjord Young Investigator Award from the Academy of Clinical Physicians and Scientists in 2008. He published multiple papers in peer-reviewed, high-impact factor journals including Leukemia, PNAS, Immunity and Molecular Cell and received the Cancer Research Foundation Young Investigator Award in 2014.

Abstract:

Chemical modifications of DNA/histone play an important role in organization of human chromatin into distinct structural domains that control gene expression, stem cell differentiation and tumorigenesis. Drugs that target various chromatin modifiers have become one of the promising treatments for many types of cancer including solid tumors and hematologic malignancies such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, most, if not all, of the cancers treated with epigenetic drugs eventually develop drug resistance and render epigenetic drugs ineffective in cancer patients. The mechanisms underlying the selectivity and efficacy of epigenetic-modifying drugs are still unknown. Therefore, a major challenge in today’s cancer treatment is to unravel the mechanisms of drug resistance and to develop strategies to prevent or reverse drug resistance in various types of cancer. In this study, we developed a new method to simultaneously measure 5-methylcytosine(5-mC) and hydroxymethylcytosine (5-hmC). CDMIAs revealed significantly drug-responsive changes in 5-mC/5-hmC at the promoters of differentiation/lineage-controlling genes such as PU.1/SPI1. Immunoprecipitation experiments demonstrated lineage-specific, drug-sensitive interactions between the PU.1/SPI1 and GATA1 transcription factors and the DNA/histone modifying complexes. ChIP-seq and chromatin conformation capture (3C) showed thatdistinct chromatin structures at the gene locus in a lineage-specific manner. Importantly, novel mutations in TET2,TET3, DNMT3L and PU.1/SP1 were revealed by genome-wide sequencing and confirmed by Sanger sequencing. These mutations correlated with the altered interactions between PU.1/SPI1 and the DNA/histone modifying complexes and predicted the responses to epigenetic modifying drugs. Examination of clinical specimens from patients with MDS confirmed the presence of distinct lineage/differentiation-specific chromatin structures These results demonstrate the importance of functional genomics in the pathogenesis of MDS and leukemia and may identify novel therapeutic targets.

Miguel Paredes-Serrano

Hospital Angeles de Querétaro, Universidad Anahuac Campus Querétaro, Mexico

Title: The use of molecular pathology for pediatric cancer diagnosis
Speaker
Biography:

Miguel Paredes-Serrano is a Pediatric Pathologist. Graduated from Military School of Medicine in Mexico, he made his pathology Residence in the Military Central Hospital and subspecialty in the Pediatric National Institute. He is active member of the USCAP since 2003. During the last years, he has served as a Pediatric Pathologist in an Oncologic Pediatric Hospital and in Private Practice. He is Director of Pathology in the Hospital Angeles de Querétaro and Histology and Pathology Professor in the School of Medicine at Universidad Anahuac, campus Querétaro, Mexico.

Abstract:

Pediatric cancer involves a complex spectrum of biologically diverse diseases that are different from those cancers seen in adults. Some of the malignant solid tumors diagnosed in children are, for example, the result of developmental pathways dysregulation and mimic stages of organogenesis. Some of them are associated with developmental disorders and congenital syndromes. Otherwise, some Central Nervous System, hematopoietic and lymphoid malignancies seen in Children, show different molecular disorders, and thus differs from their Adult histological counterpart. The knowledge of this is important because of the use of some target therapies used to treat them. The systematic use of genomic, expression and other molecular profiling technologies, together with the use of experimental tumor model systems, are improving our understanding of the biology of these diseases. The modern pathologist must integrate the information obtained from the patient´s Clinical history and image tests, together with genetic and molecular analyses of pediatric tumors in order to allow the recognition of distinct clinical tumor subtypes, as well as potential therapeutic targets for some of these neoplasms. That´s why, the new tumors classification systems are now incorporating these techniques into diagnostic algorithms, for tumor classification, risk stratification, and disease monitoring. They must be, therefore part of the tools that the pathology for diagnostic purposes.

Speaker
Biography:

Dipak Ramji received his BSc (Hons) degree (Biochemistry) and his PhD from University of Leeds. This was followed by post-doctoral research at the EMBL (Heidelberg) and IRBM (Rome) with fellowships from the Royal Society and the EU. He joined Cardiff University in 1992 and is currently a Reader at Cardiff School of Biosciences. His research is focused on understanding how the immune and inflammatory responses regulate macrophage processes in atherosclerosis with the goal of attaining deeper mechanistic insight and identifying preventative/therapeutic agents. He has published over 80 peer-reviewed papers, reviews and book chapters (h-index = 30; i10-index = 57). He is an Editorial Board member of 16 international journals.

Abstract:

Atherosclerosis, an inflammatory disorder of medium and large arteries and the underlying cause of myocardial infarction and cerebrovascular accident, is responsible for more deaths worldwide than any other disease. Pharmaceutical intervention together with lifestyle changes have recently resulted in a slight reduction in morbidity and mortality from atherosclerosis and its complications, at least in the western world. However, this is expected to change in the future because of global increase in risk factors such as obesity and diabetes. Current pharmaceutical therapies against atherosclerosis such as statins are not fully effective and associated with several side effects together with patient-dependent efficacy. Unfortunately, many pharmaceuticalleads against established targets have proved disappointing at the clinical level (e.g. inhibitors against cholesterol ester transfer protein). It is therefore essential that further research is carried out into alternative therapies for the prevention and/or treatment of atherosclerosis.

Nutraceuticals have recently received substantial interest for the prevention/treatment of atherosclerosis (see our article in Nature Reviews Cardiology 13, 2016, 513-32). However, more in-depth understanding is required on the molecular mechanisms underlying the actions of nutraceuticals together with large clinical trials testing their efficacy.We have recently initiated studies on the effects of many nutraceuticals, including certain omega-6-fatty acids, polyphenols and flavanols, on several key monocyte/macrophage processes associated with atherosclerosis in vitro(e.g. monocytic migration, macrophage polarization, foam cell formation, activation of inflammasome and production of reactive oxygen species) and various risk factors in vivo. These will be presented in the context of current therapies and those that are being developed.

Speaker
Biography:

Melanie Yong is the Senior Manager at Integrated Molecular Diagnostics Pathology, Inc. (IMD Path). She earned her Bachelor of Science in Biomedical Sciences and Microbiology from Colorado State University and certified by American Society for Clinical Pathology (ASCP) Board of Certification in Molecular Biology, MB (ASCP)CM. She is committed to the highest standard of excellence and enjoys the challenges that come along with new science and technology in the advancing biotechnology and clinical diagnostics field. Her current research focuses in cancer genomics.

Abstract:

Comprehensive genetic profiling of tumors using next generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test that integrates results from NGS with those more traditional results obtained by immunohistochemistry (IHC) of solid tumor tissues. Relevant regions of genes known to be implicated in solid tumors are targeted for deep sequencing.  The tight concordance between some somatic mutations and the standard-of-care (SOC) therapeutics administered in clinical practice makes identification of such mutations in a specific tumor invaluable in guiding personalized and rational treatment of the patient.  The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon and melanoma, followed by a full report that includes drug candidates available through clinical trials.  For all other tumor types, a full report is provided. Our Integrated 152 solid tumor panel not only detects single nucleotide polymorphisms (SNPs), but will identify copy number variations (CNVs) and some translocations in 152 cancer-related genes. We describe the standardization, validation, and clinical utility of the Integrated 152 Solid tumor test on approximately 250 solid tumor formalin-fixed paraffin-embedded (FFPE) disease samples and control cell-line samples. These studies showed high reproducibility and accuracy (~99%). When therapeutics in clinical trials were included, clinically relevant recommendations increased to 95% for patients in advanced stages of cancer. We present data to demonstrate how the Integrated 152 Solid Tumor Test may be used in clinical practices.

Speaker
Biography:

Leyla Bahar, after graduating from Cukurova University Faculty of Medicine, she worked as a medical practitioner in Mersin until 2002. In Department of Histology-Embryology she completed PhD in Mersin University Faculty of Medicine in 2008. She has published more than 20 papers and announcement in journals and has been serving as a consultant editor and editorial board member of reputable. Leyla Bahar still continues to work as a scientist and an assistant professor at Mersin University who is working on many issues and as peer-review in journals.

Abstract:

Colorectal cancer (CRC) arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes. The molecular changes occurring during the development of the tumor must be investigated in order to understand the carcinogenesis. The cyclooxygenase (COX) isoenzymes, COX-1 and COX-2, catalyze the formation of prostaglandins, thromboxane, and levuloglandins. COX-2 is induced by inflammatory and mitogenic stimulants and prevails on tumor carcinogenesis by increasing the prostaglandin synthesis in inflammatory and neoplastic tissues. The aim of this study was to investigate the association the COX-2 gene -1195 A>G polymorphism and CRC risk. We also investigated the relationship between the COX-2 gene mRNA levels in peripheral blood monocytes and -1195 A>G polymorphism in CRC. Ninety individuals with CRC and 106 healthy individuals are included in our study. The genotypes are determined by using PCR-RFLP. RNA of individuals with CRC is isolated and RT-PCR is applied. Genotype distribution and allelic frequencies for -1195 A>G polymorphism of COX-2 gene weren’t significantly different between patients and controls. COX-2 gene mRNA levels and genotype distributions of this polymorphism no difference between CRC patients and controls. While one of the other factors of developing CRC; the advanced age and male gender increases the risk of developing CRC, BMI, smoking and alcohol intake have no affect on risk of developing CRC. Our study is the first study to investigate the relation between -1195 A>G polymorphism and mRNA levels of COX-2 gene in CRC in Turkish population.

Speaker
Biography:

Nazan Eras; after graduate from Dicle University Faculty of Medicine, she worked as a general practitioner. She completed her MSc in 2006 and PhD in 2012 at Mersin University Faculty of Medicine, Department of Molecular Biology and Genetics. She has been serving as peer reviewer in journals. Nazan Eras still continues to work as scientist and assistant professor at Mersin University Medical Faculty, Department of Medical Genetics. Her research interests include clinical cancer genetics, human molecular genetics and oxidative stress.

Abstract:

For understanding of leukemia and treated with early diagnosis, it should be investigated moleculer changes that occur during the development of leukemia. Apoptosis is central to the development and homeostasis of the hematopoietic system. Previous studies have reported that leukemia cells invariably have abnormalities in one or more apoptotic pathways. The current study investigated the relationship between polymorphisms of caspase 3 G>T rs4647601 and  caspase 9 A>G rs4645978 and leukemia. Besides that we aimed to determine caspase 3 and caspase 9 enzyme levels possible effects on the risk of developing leukemia. The case group consisted of 100 patients (mean age:56±03) who had been newly diagnosed with leukemia at  the Department of Hematology, Mersin University Faculty of Medicine, Turkey. The control group comprised of 100 healthy properly age and sex matched individuals (mean age:54±15) with a no history of leukemia. The genotypes detected by using Real-Time PCR. We measured enzyme levels of caspase 3 and 9 in serum which obtained from blood samples. No significant association was observed between caspase 3 G>T rs4647601 and caspase 9 A>G rs4645978 polymorphisms and leukemia. We found that median levels of caspase 3 and 9 were higher in leukemias  than in normal blood cells (P <0.001). This is the first study reporting the detailed distribution of alleles and genotypes of caspase 3 and caspase 9 in leukemia patients in Turkish population.  Taken together, we conclude that caspase 3 and caspase 9  levels may useful for the early diagnosis of leukemia.