Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 8th World Congress on Molecular Pathology San Diego,California,USA.

Day 1 :

Molecular Pathology 2017 International Conference Keynote Speaker Shahla Masood photo
Biography:

Shahla Masood is a Persian-born Physician, who is currently the Professor and Chair of the Department of Pathology and Laboratory Medicine and Medical Director of the UF Health Breast Center at the UF College of Medicine, Jacksonville. As an internationally recognized expert in breast cancer diagnosis and prognosis, she has lectured extensively in over 50 countries, has authored numerous publications, book chapters, and textbooks, and is the recipient of countless educational and scientific awards. She has been named as one of the Top Doctors in America, Top Doctors in Cancer, and the Top 20 Most Influential Professors in Oncology.

Abstract:

Risk assessment has become an integral part of multi-disciplinary breast care, and breast cancer risk reduction interventions, and identification of high risk individuals have received a great deal of attention. Atypical proliferative changes in breast epithelial cells are ranked high among various known breast cancer risk factors and have been the subject of several investigations. Breast tissue and fluid in the ductal system provides a rich source of cells and biomarkers that has the potential to measure short-term risk of breast cancer development, and assess responses to interventional prevention efforts. Minimally invasive procedures such as fine needle aspiration biopsy, ductal lavage, and nipple fluid aspiration are commonly used in breast cancer detection and research. We have established the “Masood Cytology Index” as a morphologic risk predictor and believe that the development of a novel malignancy-associated biomarker amplified by PCR will enhance our ability to stratify high-risk patients. DNA hypermethylation has been documented to be prominent using qualitative methylation specific PCR on DNA isolated from the tumor cell line. Using quantitative pyrosequencing technology, we demonstrated that there is significant hypermethylation in tumor cells versus low DNA methylation in normal tissue. The results of this study highlight the value of DNA hypermethylation as a potential marker for early breast cancer detection. More importantly, we believe that integration of this novel malignancy associated testing with morphology is of significant value in the accurate interpretation of breast cancer precursors obtained from minimally invasive procedures and may be used as a breast cancer risk predictor.

Keynote Forum

Dale D Tang

Albany Medical College, USA

Keynote: Polo-like kinase 1 (Plk1) in smooth muscle and allergic asthma

Time : 11:30-12:10

Molecular Pathology 2017 International Conference Keynote Speaker Dale D Tang photo
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 an Editorial Board Member 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 hyper-responsiveness 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-1or AKT. Finally, smooth muscle conditional knockout of Plk1 attenuates airway resistance, airway smooth muscle hyper-reactivity 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.

Molecular Pathology 2017 International Conference Keynote Speaker Robert H Schiestl photo
Biography:

Robert H Schiestl has obtained his PhD from the University of Vienna. He was a Postdoctoral Fellow at Edmonton, Alberta, Rochester, NY, and Chapel Hill, NC, before being a Professor at Harvard, where he stayed for 10 years. Since 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 longevity. 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 wild type mice. The underlying mechanisms are 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.

  • Day 01

Session Introduction

Mark Podberezin

University of Saskatchewan, Canada

Title: Diagnostic challenges in lung neuroendocrine tumors
Speaker
Biography:

Mark Podberezin has completed his Medical School Degree (MD) and subsequent Clinical Hematology/Oncology training and PhD in Russia. Later, he did his Residency in Anatomic and Clinical Pathology at University of Illinois at Chicago and Hematopathology Fellowship at Texas Methodist Hospital in Houston. He is an Anatomic Pathologist (with special interest in Lung Pathology) and Hematopathologist at Royal University Hospital, University of Saskatchewan, Canada. He published 14 papers and presented at national, as well as international meetings.

Abstract:

Neuroendocrine tumors (NET) of the lung constitute approximately 15% of all lung tumors, with small cell lung cancer (SCLC) accounting for 15% of invasive cancers. Many of those tumors have radiological and clinical presentation which is different from other pulmonary malignancies. In most cases, diagnosis could be established by core needle biopsy and, not uncommonly, SCLC is detected by endoscopic bronchial ultrasound fine needle aspiration (EBUS-FNA). Spectrum of lung NETs includes typical carcinoid (TC), atypical carcinoid (AC), SCLC and large cell neuroendocrine carcinoma (LCNEC). Morphological criteria, separating low grade from high grade NETs, include cellular atypia, mitotic rate, and presence or absence of necrosis. The question, which has been yet unanswered and which is addressed in the presentation, is whether the above NETs represent continuum from low to high grade tumors or they are biologically different. One of the major diagnostic challenges in pulmonary NETs is their grading on core needle biopsies (CNB). It has been shown that morphological features of NET, when diagnosed by CNB, could be significantly different from the ones on same tumor upon subsequent surgical resection. This could be partially due to marked crush and processing artifact which markedly affect evaluation of mitotic rate. Measurement of proliferative rate by immunohistochemical stain for Ki67 has been approved for grading of NET in the gastrointestinal tract, but is not universally accepted in pulmonary NET. However, it can be very helpful in evaluation of CNB with marked cautery and crush artifact. In addition, CNBs may not be representative of the entire lesion and can lead to diagnostic pitfalls which will be discussed in the presentation.

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.

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.

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.

Biography:

Malgorzata Jaremko has completed her PhD in Pharmacogenomics from Wroclaw Medical University and Postdoctoral Clinical Fellowship from Mount Sinai School of Medicine, NY. She is board certified by American Board of Medical Genetics and Genomics in Clinical Molecular and Clinical Biochemical Genetics; and she is Fellow of American College of Medical Genetics and Genomics, as well as National Academy of Biochemistry. She has extensive experience in directing clinical molecular laboratories, and currently serves as the Senior Director, Clinical Laboratory & Molecular Diagnostics, and CLIA-Director of Phosphorus Diagnostics genetic testing laboratory.

Abstract:

Advances of the molecular diagnostic testing platforms, including development and implementation of NGS based genetic testing contribute to the improvement of disease prediction, diagnosis, and treatment. However, the future of genomic medicine relies on the capability of molecular genetics laboratories to develop and validate evidence-based and cost-effective laboratory tests. These laboratories face many challenges including establishing clinical utility, validating analytical performance of laboratory developed tests, and managing costs of platform development and subsequent consumables. Along with the molecular and instrumentation challenges, laboratories are faced with a myriad of software options (e.g., Galaxy, Amazon, GATK, BaseSpace, and Clarity) when establishing a reliable bioinformatics pipeline and LIS system. Finally, there is a lack of consensus and consistency in the quality standards across the industry (e.g., read depth, variant curation, and clinical validation structure). In this study, we present a framework for the consistent development of accurate, high-quality, NGS diagnostic tests. Our process is broken into stages from gene selection through clinical validation and implementation. Based on the experience in our own CLIA-laboratory, we present lessons learned in the development of NGS targeted panels for sequencing and CNV analysis for various indications including infertility, hereditary cancers, arrhythmias, cardiomyopathies and lipidemias.

Speaker
Biography:

Melanie Yong is the Senior Manager at Integrated Molecular Diagnostics Pathology, Inc. (IMD Path). She earned her Bachelor’s 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 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 was 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.