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Extracellular RNA in Drug and Diagnostic Development 2016 - 의약품 및 진단법 개발에서의 세포외 RNA 2016 -
2016년 4월 5일 - 2016년 4월 6일
미국 매사추세츠주 케임브리지, Hyatt Regency Cambridge
Extracellular RNA in Drug and Diagnostic Development

바이오유체에 포함되는 세포외 RNA(exRNA)는 정상적인 세포 과정과 그렇지 않은 세포 과정 양측에 관한 풍부한 정보를 제공합니다. 특히 세포외 소포에 둘러싸여 열화하기 어려운 exRNA는 세포간 정보 전달에 관련되어 있으며, 암 및 심혈관질환, 신경변성질환의 진단 바이오마커 및 예후 바이오마커로서 이용할 수 있습니다. Cambridge Healthtech Institute(CHI)가 주최하는 제2회 Extracellular RNA in Drug and Diagnostic Development에서는 엑소좀 및 미세소포, 혈중 순환 마이크로RNA 등의 논코딩 RNA를 이용한 비침습적 진단의 새로운 영역에서의 최신 연구 성과가 발표되며, 표준화, 프로파일링, 데이터 분석 문제 등에 대해 논의합니다.

첫째날 | 둘째날

4월 5일(화)

12:00 컨퍼런스 등록


바이오마커 및 진단법으로서의 세포외 RNA

1:15 의장 개회사

Manikkam Suthanthiran, M.D., Stanton Griffis Distinguished Professor, Medicine; Chief, Division of Nephrology and Hypertension, Weill Cornell Medical College

1:20 미국국립보건원(NIH)의 세포외 RNA에 의한 세포간 정보 전달에 대한 연구 프로그램:치료와 바이오마커 개발을 위한 exRNA

Danilo A. Tagle, Ph.D., Associate Director for Special Initiatives, National Center for Advancing Translational Sciences, National Institutes of Health

Extracellular RNA (exRNA) can act as endocrine signals to alter the phenotypes of target cells, and represents a novel paradigm in intercellular signaling. RNAseq analyses have identified a diverse population of exRNA that have been linked to regulation of the epigenome which could have profound implications for a wide range of physiologic and pathologic processes. The NIH Extracellular RNA Communication program supports research in exRNA-based biomarker and therapy development, as well as understanding fundamental principles of their biogenesis, distribution, uptake and function.

1:50 암의 기능성 바이오마커로서의 OncomiR

Frank Slack, Ph.D., Director, Institute for RNA Medicine, Department of Pathology, BIDMC Cancer Center, Harvard Medical School

MicroRNAs are excellent candidates for human biomarker studies because their signature short sequences can be easily identified, they are stable in tissue and body fluids, and their expression patterns can be rigorously detected and quantified without harm to the individual. MicroRNAs have been found in multiple body fluids, such as serum and plasma, making them an attractive option for studying non-invasive, blood-based biomarkers. These circulating miRNAs are resistant to RNases and are in fact very stable in an extracellular environment, as they can be packaged in microvesicles, exosomes, or apoptotic bodies. Indeed, profiles of plasma and serum miRNAs have been linked to numerous cancers, and diabetes, indicating that miRNAs are a new class of blood-based biomarkers of human diseases.

2:20 인간의 동종이식편 상태를 예측하기 위해 사용 가능한 세포외 RNA 개요

Manikkam Suthanthiran, M.D., Stanton Griffis Distinguished Professor, Medicine; Chief, Division of Nephrology and Hypertension, Weill Cornell Medical College

Liver transplantation is the only lifesaving therapy for patients with irreversible liver failure. A frequent post-transplant complication is acute rejection, currently diagnosed by invasive needle biopsy of the liver allograft. Because miRNAs may serve as biomarkers of clinical disease, we investigated whether circulating extracellular miRNAs in the serum of liver transplant recipients predict human liver transplant status. Our findings support the hypothesis that measurement of circulating levels of extracellular miRNAs offers a noninvasive means of monitoring lifesaving liver transplants.

2:50 스폰서 제공 프레젠테이션(연사 모집 중)

3:05 전시회장 휴식시간, 포스터 발표 관람

3:45 폐암 진단을 위한 말초혈단핵세포 마이크로RNA 바이오마커

Feng Jiang, M.D., Ph.D., Professor, Pathology, University of Maryland School of Medicine

Tremendous efforts have been made to develop cancer biomarkers by detecting circulating extracellular miRNAs directly released from tumors. Yet none of the cell-free biomarkers has been accepted to be used for early detection of non-small cell lung cancer (NSCLC). Peripheral blood mononucleated cells (PBMCs) act as the first line of defense against malignancy in the immune system; their dysfunction may occur as an early event in cancer immunogenicity or immune evasion. We proposed to investigate if differential miRNA expressions of PBMCs have diagnostic utility for NSCLC. In a testing set of 56 NSCLC patients and 46 controls, the performance of the biomarkers was reproducibly confirmed and independent of disease stage. The study presents the first in-depth analysis of PBMC miRNA profile of NSCLC patients. The assessment PBMC miRNAs may provide a new diagnostic approach for the early detection of NSCLC.

4:15 알츠하이머병을 위한 바이오마커로서의 뇌척수액 중 마이크로RNA

Julie Saugstad, Ph.D., Associate Professor, Anesthesiology & Perioperative Medicine, Oregon Health & Science University

Alzheimer's disease (AD) is the most common form of dementia. There are currently no clinical biomarkers to confirm the onset of AD, but such a tool would allow earlier initiation of treatments that can slow disease progression. Here, we describe our efforts to identify extracellular microRNAs circulating in cerebrospinal fluid obtained from living donors to serve as biomarkers for AD using quantitative RT-PCR platforms for discovery and validation studies.


전사체 해석과 데이터 리소스

4:45 전사체 해석

Mark B. Gerstein, Ph.D., Albert L. Williams Professor, Biomedical Informatics, Yale University

This presentation will cover RNA-seq pipelines, RNA-seq clustering techniques, and privacy considerations for RNA-seq data.

5:15 exRNA Communication Consortium(ERCC)가 개발한 RNA-Seq 파이프라인, 패스웨이 해석 툴, 데이터 리소스에 의한 세포외 RNA 기능의 연구

Matthew Roth, Ph.D., Assistant Professor & Co-Director, Bioinformatics Research Lab, Baylor College of Medicine; Data Management & Resource Repository of the Extracellular RNA Consortium (NIH)

The NIH funded extracellular RNA Communication Consortium (ERCC) brings together experts in exRNA biology, human disease, bioinformatics, biomarker discovery, and therapeutic development to better understand exRNA biology and potential clinical applications. A key ERCC mission is the development of analytical pipelines and data resources for the broader scientific community. A description of these resources and their application to exRNA analyses will be presented.

5:45 쇼트코스 등록


추천 디너 쇼트코스 *

4월 5일(화), 18:00-21:00
(쇼트코스 3) 면역 반응에서의 마이크로RNA

* 별도 참가 등록 필요


첫째날 | 둘째날

4월 6일(수)

7:45 브렉퍼스트 프레젠테이션


바이오마커 및 치료법으로서의 세포외 소포의 가능성

8:25 의장 발언

Peter J. Quesenberry, M.D., Director of Research, Division of Hematology/Oncology, Paul Calabresi M.D. Professorship in Oncology at the Warren Alpert Medical School of Brown University and Rhode Island Hospital

8:30 세포외 소포를 이용한 치료법으로서의 마이크로RNA

Peter J. Quesenberry, M.D., Director of Research, Division of Hematology/Oncology, Paul Calabresi M.D. Professorship in Oncology at the Warren Alpert Medical School of Brown University and Rhode Island Hospital

Extracellular vesicles represent a new mode of intercellular communication. We have studies showing that “toxic” endothelial progenitors induced by vesicle exposure can induce pulmonary hypertension (PH) and that mesenchymal stem cell (MSC) derived vesicles can reverse PH. Similarly, normal or MSC vesicles can reverse ischemia-reperfusion renal injury and radiation injury to murine marrow stem cells. MSC or normal vesicles can also reverse the malignant phenotype of prostate and colorectal cancer.

9:00 세포외 RNA와 엑소좀에 의한 종양 미세환경의 암유전자 패턴 해석

James G. Patton, Ph.D., Professor, Biological Sciences, Vanderbilt University

Mutant KRAS induces trafficking of EGF receptor (EGFR) and the EGFR ligand amphiregulin to exosomes and drastically changes exosomal protein content, leading to activities that can alter the tumor microenvironment. We characterized small RNAs from cells and matched exosomes that differ only in KRAS status. Exosomal small RNA profiles were distinct from cellular profiles, and mutant KRAS exosomes clustered separately from wild-type KRAS exosomes. miR-100 levels were increased in mutant KRAS cell-derived exosomes and delivery of exosomes with miR-100 downregulated mTOR in recipient cells. Selective trafficking of miRNAs into exosomes appears to be dependent on KRAS-MEK signaling effects on Argonaute 2, a key component of RNA-Induced Silencing Complexes. Besides extracellular RNA transfer, we find that mutant KRAS derived exosomes confer metabolic-altering activity to cells in vitro and in vivo. These findings have implications for non-cell autonomous effects of cancer on the tumor microevironment and the cancer field effect.

9:30 스폰서 제공 프레젠테이션(연사 모집 중)

9:45 암진단, 예후, 역학에서 세포외 소포의 현황과 향후 가능성

Mukesh Verma, Ph.D., Chief, Methods and Technologies Branch, National Cancer Institute, National Institutes of Health

Both normal and diseased cells continuously shed extracellular vesicles (EVs) into extracellular space, and the EVs carry molecular signatures and effectors of both health and disease. EVs reflect dynamic changes that are occurring in cells and tissue microenvironment in health and at a different stage of a disease. EVs are capable of altering the function of the recipient cells. Trafficking and reciprocal exchange of molecular information by EVs among different organs and cell types have been shown to contribute to horizontal cellular transformation, cellular reprogramming, functional alterations, and metastasis. EV contents may include tumor suppressors, phosphoproteins, proteases, growth factors, bioactive lipids, mutant oncoproteins, oncogenic transcripts, microRNAs, and DNA sequences. Therefore, the EVs present in biofluids offer unprecedented, remote, and non-invasive access to crucial molecular information about the health status of cells, including their driver mutations, classifiers, molecular subtypes, therapeutic targets, and biomarkers of drug resistance. In addition, EVs may offer a non-invasive means to assess cancer initiation, progression, risk, survival, and treatment outcomes. The goal of this review is to highlight the current status of information on the role of EVs in cancer, and to explore the utility of EVs for cancer diagnosis, prognosis and epidemiology.

10:15 휴식시간

10:45 대형 온코좀(Oncosomes):암세포간 정보 전달에 관한 새로운 연구 분야

Dolores Di Vizio, M.D., Ph.D., Associate Professor, Surgery, Biomedical Sciences, Pathology & Laboratory Medicine, Cedars-Sinai Medical Center; Associate Professor, Medicine, University California, Los Angeles; Assistant Professor, Boston Children's Hospital, Harvard Medical School

Our team recently reported that highly metastatic cells export large (1-10 µm diameter) bioactive EVs (large oncosomes) that originate from the shedding of bulky membrane protrusions from the plasma membrane. We have demonstrated that the abundance of large oncosomes in the circulation and in tissues correlate with advanced disease in mouse models and human subjects. Large-scale profile analyses demonstrate that large oncosomes represent a novel population of EVs enriched in tumor-derived molecules. Large oncosomes are thus valuable candidates for new biomarker profiles to be developed using tissue- and blood-based assays in combination.

11:15 맞춤형 의료에서의 혈중 순환 바이오마커 임상 평가

Shidong Jia, Ph.D., Scientist, Oncology Biomarker Development, Genentech

The enumeration and characterization of circulating tumor cells (CTCs), exosomes and circulating tumor-free DNA (ctDNA) in the peripheral blood provide important prognostic and diagnostic information in personalized cancer care. Specific examples will be shown to demonstrate the opportunities and challenges for the development of circulating biomarkers in cancer.

11:45 인간의 신경세포와 신경교세포 배양에서 엑소좀 논코딩 RNA 발현의 계통적 프로파일링

Nikolaos Mellios, M.D., Ph.D., Assistant Professor, Neurosciences, University of New Mexico School of Medicine

Although ignored until recently for not complying with the central dogma of molecular biology, non-coding RNAs (ncRNAs) are emerging as important novel epigenetic regulators of diverse cellular processes. Recent work has revealed the presence of small secretory microvesicles known as exosomes that contain both protein and RNA of the cell of origin and are particularly enriched in ncRNAs. The presence of exosomes in both glia and neurons, and their perceived ability to influence various aspects of neuronal and glial development and function, has positioned them as an exciting and novel method of cell-to-cell communication with important implications for brain disease therapeutics. However, to date, little is known about the exosomal ncRNA expression profile of human neurons and glia. We measured the expression of multiple subtypes of ncRNAs in exosomes isolated from stem cell-derived neuronal and astrocytic cultures, as well as human microglial cultures. Ongoing work is aiming at characterizing the cell-specificity of exosomal ncRNA expression and the association between ncRNAs and protein coding genes secreted by exosomes.

12:15 런천 프레젠테이션 또는 개별 점심식사


장쇄 논코딩 RNA와 논코딩 RNA의 가능성

1:25 의장 발언

Da-Zhi Wang, Ph.D., Associate Professor, Cardiovascular Research Division, Department of Cardiology, Boston Children's Hospital, Harvard Medical School

1:30 심혈관질환에서의 논코딩 RNA

Da-Zhi Wang, Ph.D., Associate Professor, Cardiovascular Research Division, Department of Cardiology, Boston Children's Hospital, Harvard Medical School

Thousands of long non-coding RNAs (lncRNAs) have been discovered; however, the role of most lncRNAs in heart failure remains largely unknown. We performed RNA deep sequencing from cardiac samples of patients with ICM and controls. Expression correlation coefficient analyses revealed a strong association between lncRNAs and extracellular matrix (ECM) protein-coding genes. Gain- and loss-of function studies demonstrate that lncRNAs are important regulators of fibrosis. Our results indicate that lncRNAs may represent novel regulators of heart function and cardiac disorders, including ischemic cardiomyopathy.

2:00 장쇄 논코딩 RNA와 종양 억제 작용

Nadya Dimitrova, Ph.D., Assistant Professor, Molecular, Cellular, and Developmental Biology, Yale University

There is an unmet need to gain a deeper understanding of the in vivo biology of lncRNAs that are deregulated in disease states, such as cancer. Our laboratory uses genetic approaches to study a subset of lncRNAs that are directly regulated by the important tumor suppressor protein, p53. Our analyses reveal that lncRNAs influence the expression of proteins in the p53 pathway and play key roles in the physiological response to stress and in tumor suppression.

2:30 논코딩 RNA를 이용한 암세포 취약성의 식별

Alexander Pertsemlidis, Ph.D., Associate Professor, Pediatrics and Cellular & Structural Biology, University of Texas Health Science Center at San Antonio

To identify ncRNAs that regulate tumor cell viability, we have combined a high-throughput screening platform with libraries of chemically synthesized ncRNA mimics and inhibitors. Candidate targets are validated using qRT-PCR, protein quantification, and luciferase reporter assays. The response of cancer cells to perturbations in candidate ncRNA levels is assessed through flow cytometric analysis of cell cycle phase distribution and through colony formation and caspase activation assays, and validated in mouse xenograft models. We have identified ncRNA mimics and inhibitors that have significant effects on cell viability and drug response. While these ncRNAs may have intrinsic value as biomarkers or therapeutic agents, the vulnerabilities that they uncover are also of value, in that they can be targeted directly with pathway-specific perturbations.

3:00 컨퍼런스 폐막



첫째날 | 둘째날

* 주최측 사정에 따라 사전 예고없이 프로그램이 변경될 수 있습니다.

 

 


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