2015 ISCP-China Biomedical Workshop Workshop Programme

2015 ISCP-China Biomedical Workshop

Workshop Programme March 19th 2015

Welcome to the 2015 ISCP China Biomedical Workshop

Kind Reminder

Dear Sir or Madam,

Thank you very much for attending the 2015 ISCP China Biomedical, held at Academic Hall, 13th Floor, No. 10 Building, Guangzhou Medical University, 195, Dongfeng Xi Road, Guangzhou City, China. This workshop is supported by a research grant from Science Foundation Ireland (SFI) under the ISCA Grant number SFI/13/ISCA/2845.

Please read the following reminders:

1. Emergency Contact for Committee Affairs ISCP Programme Coordinator: Dr. Yinya Liu (+86-18611677216) GMU Contact Person Ms. Xiaojie (Jessica) Ma (+86- 13751885838)

2. Attention  Please be present at the workshop and attend relevant activities on time;  Please ensure that your mobile phone is always silent at the Conference hall;  Please wear your delegate badge when you are present at the workshop, attend relevant activities or have meals;  Please take good care of your money, identity card, etc. and take the room key/card with you when leaving the room  Please feel free to ask for any help from our staff.

温馨提示

尊敬的各位领导、专家：您好！欢迎您参加爱尔兰国际合作项目和广州医科大学联合举办的“2015 ISCP 中国爱尔兰生物医药研讨会 ” 会议由爱尔兰科学基金会(SFI)资助，资助项目代码 SFI/13/ISCA/2845。为保证会议顺利进行，请您阅读以下内容： 1. 应急联系人 ISCP 项目：刘茵雅老师 +86-18611677216 广医：马晓洁老师：+86-13751885838

2. 注意事项：请按照日程安排，准时出席会议和参加相关活动；会场内，请关闭手机或调至震动状态；出席会议、参加相关活动和就餐时请佩戴胸卡；有事请联系工作人员。

General Information Workshop Venue: Academic Hall, 13th Floor, No. 10 Building, Guangzhou Medical University, 195, Dongfeng Xi Road, Guangzhou City, China

Official website: 中文网址 http://www.gzhmc.edu.cn/ English website: http://www.gzhmu.edu.cn/gyEnglish/index.html

Oral Presentations Time Limit Each presentation time indicated on the Program includes speech and Q&A sessions (please refer to the Program). Please adhere to the time allocated for your presentation

Presentation File Submission We strongly advise presenters to submit your talk online in advance, or bring the presentation file on a USB flash drive and copy it to the conference computer during on- site registration or before each session.

The Academic Hall will be equipped with all necessary equipment for presenting Powerpoint and PDF based presentations.

Name Badge For identification purpose, badges for speakers are expected to be worn at all times during the Workshop.

Meal

Lunch Buffet is only provided for speakers Lunch boxes are provided for all general participants

Workshop Programme 19th March 2015

Time 9.00-9.30 Registration

9.30-12.00 Session 1 - Towards understanding the molecular mechanisms of disease

Chair: (Sinead Miggin, Maynooth University, Ireland)

9.30-9.50 Niamh Moran (Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland)

Differential Platelet Activation by Metastatic versus Non-Metastatic Cancer cell lines: A multiplex analysis

9.50-10.10 Tao Peng (Innate immunity and human diseases, Therapeutics targeting innate immunity; Director of Sino-French Hoffmann Institute, Guangzhou Medical University)

Molecular Mechanisms of Hepatitis C Virus-Host Interactions

10.10-10.30 Dermot Cox (Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland)

Platelets and Innate Immunity

10.30-10.50 Xu Xin (Sinnowa Medical Science & Technology Co., Ltd, Nanjing China)

Brief introduction of an Innovative Platelet Function Testing Analyzer and its application

10.50-11.10 Jian Wang (Internal Medicine (respiratory disease), Director, Department of Scientific Research, Guangzhou Medical University )

Sodium Tanshinone IIA Sulfonate (STS) on Pulmonary Hypertension (PH): From Basic Research to Clinical Trial

11.10-11.30 Richard Porter (School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland)

The Role of Mitochondrial Uncoupling Proteins (UCP’s) in Thymocyte/T-Cell Development and Function

12.00-13.00 Lunch (Speakers Only: VIP Room) (General Participants: Lunch boxes)

13.00-14.50 Session 2 – Genetics of Disease Chair: (Paul Dowling, Maynooth University, Ireland)

13.00-13.20 Weiping Liao (Neuroscience, Director of Institute of Neuroscience, Guangzhou Medical University)

Epilepsy Genetics: Generalized Epilepsy VersusPartial Epilepsy

13.20-13.40 David Hughes (Centre for Systems Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland)

Association of selenium status and selenoprotein gene variation with colorectal cancer risk

13.40-14.00 Mark McCormack (Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland)

Pharmacogenomics research in epilepsy: finding genetic predictors of clinical response to AEDs

14.00-14.20 Jiachun Lu (Epidemiology, Dean of School of International Education, Guangzhou Medical University)

Links between COPD and Lung cancer

14.20-14.40 Sinead Miggin (Institute of Immunology, Maynooth University, Maynooth, Ireland)

Toll-like receptor expression in Osteoarthritis

14.50-15.30 Coffee/Tea and Poster Viewing

15.30-17.30 Session 3 - Biomarker discovery and Translational biology Chair: (Dermot Cox, Royal College of Surgeons in Ireland)

15.30-15.50 Paul Dowling (Department of Biology, Maynooth University, Maynooth, Ireland)

Oncoproteomics - preparing for the challenges ahead

15.50-16.10 Jinbao Liu (Pathophysiology, Dean, Graduate School, Guangzhou Medical University)

Target swith from DNA to Protein makes platinum a more attractive anti-cancer agent

16.10-16.30 Markus Rehm (Centre for Systems Medicine, Department of Physiology and Medical Physics Royal College of Surgeons in Ireland)

From cancer cell biology and systems biology to systems medicine

16:30-16:50 Robert Elmes (Department of Chemistry, Maynooth University, Ireland)

Thiosquaramides: A new class of pH switchable anion transporter

16:50-17:10 Yiguo Jiang (Environment Health, Deputy Dean, School of Public Health, Guangzhou Medical University)

The Roles and Mechanisms of MicroRNAs in Chemically Induced Carcinogenesis

17:30-20:00 Closing reception and networking

Introduction to International Strategic Collaboration Programme

National University of Ireland Maynooth (NUIM) is leading a joint collaboration with Dublin City University (DCU), the Royal College of Surgeons in Ireland (RCSI), Trinity College Dublin (TCD) and the Dublin Institute of Technology (DIT). This collaboration, called the International Strategic Collaboration Programme, supports the development of new and existing joint research opportunities between Irish universities and partner organisations in China. The programme is focusing on collaboration in three thematic research areas: biomedical science, information and communication technology, and nanotechnology, and has been made possible by a Science Foundation Ireland International Strategic Collaboration Award.

爱尔兰国际战略合作项目简介

爱尔兰国立大学梅努斯和其他四所机构：都柏林城市大学，都柏林圣三一学院，

都柏林理工大学，爱尔兰皇家外科学院共同获得爱尔兰科学基金会的资助。这笔资金

主要是通过 ISCP 中国项目建立和提高爱尔兰的合作伙伴与中国高校的联合研究活

动。我们项目的目标是加强和拓宽和现有顶尖中国机构在信息和通讯技术，生物医药

科学以及纳米技术三个领域的合作。我们也希望能在两国的研究团体之间能有更好的

文化理解，这对将来的学术和商业合作都至关重要。

Introduction to Guangzhou Medical University (GMU)

Guangzhou Medical University (GMU), formerly known as Guangzhou Medical College, founded in 1958，is a medical institution which offers a full range of programmes at graduate and undergraduate levels. The main campus of Guangzhou Medical University is located in the downtown of Guangzhou City, a stone's throw away from Liuhua Lake Park and Yuexiu Mountain. A new campus of approximately 247 acres is situated in Panyu District of Guangzhou City near Pearl River, which is an ideal place for learning and research.

GMU boasts 15 schools: School of Basic Sciences, School of Pharmaceutical Sciences, School of Health Management, School of Public Health, School of Nursing, Graduate School, School of International Education, School of Dentistry, Kingmed College of Laboratory Medicine, The School of General Practice and Continuing Education, Health Vocational and Technical College, The First Clinical School, The Second Clinical School, The Third Clinical School, The Fourth Clinical School.

GMU has 8 directly affiliated hospitals and 11 non-directly affiliated hospitals, which specialise in respiratory diseases, neuropathy, cardiovascular diseases, gynecology and obstetrics, cancer, dental care, rehabilitation, minimally invasive surgery, primary care and so on. GMU boasts one national clinical research centre and nine national key clinical specialties in our directly affiliated hospitals: The First Affiliated Hospital: allergic reaction, oncology, respiratory medicine, thoracic surgery, urology, intensive care, The Second Affiliated Hospital: pain management, allergic reaction The Third Affiliated Hospital: obstetrics.

Furthermore, GMU boasts 13 research institutes, namely, Guangzhou Institute of Respiratory Diseases, Sino-French Hoffmann Institute, Guangzhou Institute of Snake

Venom, Institute of Neuroscience, Institute for Chemical Carcinogenesis, Cancer Research Institute, Institute of Humanities and Social Sciences, Institute of Integrated Chinese and Western Medicine, Guangzhou Institute of Obstetrics and Gynecology, Guangzhou Institute of Cardiovascular Disease, Guangzhou Institute of Orthopedics, Urology Institute and Institute of Higher Education. Among them, the Sino-French Hoffmann Institute is a joint project with the 2011 Nobel Laureate Jules Hoffmann. We also have a state key laboratory for respiratory diseases which is the only one of its kind in China.

GMU has carried out collaborations in research, teaching, and training with renowned universities around the world.

广州医科大学创办于 1958 年，是一所以医学为优势和特色，开展博士、硕士、本科多层次人才培养的全日制一本高校。学校东风西校区坐落于历史文化名城--广州的中心地带，南依苍翠葱茏的越秀山，北傍风光秀美的流花湖，是读书治学的理想之地。番禺校区地处与广州大学城一江之隔的新造镇，环境优雅、设施先进、现代化气息浓郁。学校下设 16 个二级学院，8 所直属附属医院和 10 所非直属附属医院，19 个研究所/中心，19 个市级以上重点实验室，其中呼吸疾病实验室是广东省地方高校中第一个国家重点实验室。学校拥有 1 个国家重点学科，9 个国家临床重点专科，一批省级重点学科和重点专科，其中呼吸内科排名全国第一、胸外科排名全国第五，临床医学进入 ESI 排名前 1%。学校坚持“人才兴校”战略，汇聚了中国工程院院士、新世纪百千万人才工程国家级人选、长江学者讲座教授、广东省珠江学者特聘教授、国家级教学名师、国家有突出贡献专家、卫生部有突出贡献中青年专家等一批优秀教师。现有博士研究生导师 84 人，硕士研究生导师 570 人。

学校广泛开展对外学术和教育交流合作，先后与美国霍普金斯大学、加州州立大学、马里兰大学，法国斯特拉斯堡大学，英国爱丁堡大学、伯明翰大学、胡弗汉顿大学，韩国延世大学，澳大利亚昆士兰科技大学，香港大学、香港中文大学、香港理工大学，台湾义守大学、台湾中山医学大学等高等院校和研究部门开展合作办学和学术交流活动。有一批国外著名高校专家被聘为学校特聘教授、名誉教授或客座教授，在此传道授业。

Introduction to ISCP Research Consortium Partners 爱尔兰国际战略合作项目成员介绍

National University of Ireland, Maynooth (NUI Maynooth)

While formally established as an autonomous university in 1997, NUI Maynooth traces its origins to the foundation of the Royal College of St. Patrick in 1795, so that while in one sense it is Ireland’s newest university, it draws strength from a heritage that includes over 200 years of commitment to education and scholarship. NUI Maynooth is today a university of international standing, renowned for the quality and value of its research and scholarship, for its dedication to excellent teaching, and for providing an outstanding learning environment for its students. Today, the University is a place of lively contrasts, combining the peaceful and historic beauty of fine eighteenth century buildings with the dynamism and excitement of modern research and teaching facilities.

While much has changed at Maynooth over the past two centuries, the University’s commitment to scholarship and learning remains central to its mission. The University is home to outstanding academics whom have established a strong reputation for research and teaching excellence and has over 8,000 students from more than 20 countries.

NUI Maynooth has important research strengths in spatial analysis and geocomputation; applied mathematics and applied ICT; immunology, microbiology and chemical biology; historical and cultural traditions, and business innovation. The University looks outward, engaging with industry and the community to better serve students, the region and the country.

To find out more visit www.nuim.ie

Trinity College Dublin (TCD)

Trinity College Dublin was founded in 1592 with a university charter from Queen Elizabeth I and by the grant of a site by Dublin Corporation.

Trinity has expanded over the centuries to become a modern university with some 15,600 students and 3,700 staff. It is now one of the great universities of the world, widely recognized for the high quality of its graduates, the international standing of its research and scholarship, and the value it places on contributing to Irish society and the wider world.

These achievements are a source of pride for the College community, and play their part in what makes Ireland unique on the world stage. We will build on these achievements with a vision that Trinity College Dublin will be further recognized as a university of global consequence—that we will make a yet greater impact commensurate with the talents of our students and staff.

To find out more visit www.tcd.ie

Dublin City University (DCU)

DCU is a young, innovative, research-intensive and globally-engaged University. A distinctive mission to transform lives and societies through education, research and innovation underpins the delivery of over 120 programmes to 11,500 students across 4 faculties: Humanities & Social Sciences, Science & Health, Engineering & Computing and the DCU Business School. Our campus experience is international and multi-ethnic with nearly 2000 of our students coming from 116 countries around the world. DCU is known for its strong focus on social inclusion and community engagement. Currently, over 500 students from disadvantaged backgrounds are supported through the DCU Access Programme. At DCU, knowledge is translated into societal and economic impact. Our research focuses on global-grand challenges such as healthcare needs, sustainable development, multi-cultural societies and conflict resolution. Our enterprise focus is reflected in our national leadership positions in both industry-academic research and successful execution of licences arising from our intellectual property portfolio. The Generation 21 system of graduate attributes and a fundamental commitment to academic excellence ensure that DCU graduates are equipped to flourish in 21st century society. To find out more visit www.dcu.ie

Dublin Institute of Technology (DIT)

With a history stretching back over one hundred and twenty years, Dublin Institute of Technology has been recognised as a pioneer in technological higher education. The Institute’s alumni have played important roles in technical and scientific innovation, economic and social development and culture and education both in Ireland and internationally. We nurture innovation and creativity across and between academic disciplines and are committed to making education accessible to people from diverse backgrounds. We develop knowledge which benefits the sustainable development of society. DIT has a distinctive role and a comprehensive offering in the Irish higher education landscape and provides opportunities for progression for students at different stages of their careers.

Today, DIT is one of the largest Higher Education Institutes (HEIs) in Ireland, with over 14,000 full-time equivalent students. The Institute enjoys a diverse student base, where students pursue a wide range of apprenticeship, ordinary degree, honours degree, master’s and doctoral programmes. Our modularisation programme and a range of student support initiatives have enhanced the services and supports available to the student. Research activity is an increasing important component of the Institute’s work including a significant enhancement of technology transfer efforts. We continue to develop our vibrant Community Links initiative working with local communities to enhance their access to education. Organisation change designed to enhance the effectiveness and efficiency of the Institute is in train. We continue to plan for the development of DIT’s Grangegorman campus, a leading edge development representing a total investment of over €1 billion, the largest investment in higher education in the history of the state.

Building on these successes, DIT is committed to responding to the changes that have emerged in Irish higher education in recent times and embracing the consequent challenges and opportunities, including institutional collaboration, widening participation, growing community engagement and the enhancement of the internationalisation agenda within the Institute.

To find out more visit www.dit.ie

The Royal College of Surgeons in Ireland (RCSI)

Founded in 1784, RCSI is a not-for-profit, largely self-funding academic institution providing education and training in the health sciences in Ireland, Bahrain, Dubai and Malaysia. With over 3,700 students, RCSI operates the largest medical school in Ireland and provides undergraduate courses in Pharmacy and Physiotherapy.

RCSI also delivers postgraduate training and education through its Faculties of Radiology, Dentistry, Nursing, Sports & Exercise Medicine, the School of Postgraduate Studies, the Institute of Leadership as well as the National Surgical Training Centre.

The RCSI Research Institute facilitates translational research and training programmes, commercialises intellectual property arising from its research and develops collaborative links with industry, educational and research institutions globally so that advances in medical science are translated as quickly as possible into patient treatments.

To find out more visit www.rcsi.ie

Workshop Abstracts

and

Biographies

Differential Platelet Activation by Metastatic versus Non-Metastatic Cancer cell lines: A multiplex analysis Niamh Moran1, Annachiara Mitrugno1, Pat Metharom2, David Williams1 1Molecular & Cellular Therapeutics, Royal Collage of Surgeons in Ireland, Dublin 2; 2 Faculty of Health Sciences, Curtin Health Innovation Research Institute , Perth, Australia. Blood platelets play a critical role in haemostasis and thrombosis. They are activated by damaged endothelial cells or exposed collagen fibrils in damaged blood vessels. In performing their thrombotic function, they secrete bioactive agents from their dense and alpha-granules, which store ADP/ATP or relevant cytokines, respectively. The platelet releasate serves to enhance the local thrombotic events, prevent infection and facilitate wound angiogenesis.

In addition to their thrombotic function, platelets interact functionally with circulating and metastatic cancer cells. Platelets support tumour angiogenesis in animal models[1]. In addition, they act as an immunological protective shield for blood-borne tumor cells, permitting the tumor migration to distant sites. Moreover, platelet alpha-granules provide a dynamic reservoir of cytokines, which can facilitate tumour vascularization, growth and metastasis. We have demonstrated that tumour cells differentially induce platelet secretion using a luminometric assay to ATP/ADP released following platelet activation [2]. Using pairs of syngenic prostate or breast cancer cell lines, we demonstrated that metastatic tumor cells induced a quantitatively greater secretory response than non-metastatic cancer cells [3].

Evidence that platelets release a bespoke blend of relevant cytokines by selective release of alpha-granule subtypes is emerging in the literature[4]. We therefore explored the nature of the cytokine release from platelet alpha-granules in response to exposure to a standard prothtombotic agent (thrombin) or in response to stimulation with either metastatic (M) or non-metastatic (NM) human cancer cell lines. A multiplex protein array (RayBioTech) was used to identify and quantify cytokine release from healthy human platelets. We demonstrate that the composition of the platelet secretion differs depending on the metastatic potential of the activating cancer cell line (See Figure). This bespoke release of platelet-stored bioactive agents may play a crucial role in many processes driven by specific types of cancer to enhance their colonization of the host. A greater understanding of such processes will open opportunities to develop personalized treatment strategies for cancer patients in the future. Reference: 1. Ho-Tin-Noe, B., TGoerge, S Cifuni, D Duerschmied, and D Wagner, Platelet granule secretion continuously prevents intratumor hemorrhage. Cancer Res, 2008. 68(16): 6851-8. 2. Edwards, R.J., N. Moran, M. Devocelle, A. Kiernan, G. Meade, W. Signac, M. Foy, S.D. Park, E. Dunne, and D.C. Shields, Bioinformatic discovery of novel bioactive peptides. Nat Chem Biol, 2007. 3(2): p. 108-12. 3. Mitrugno, A., D. Williams, S.W. Kerrigan, and N. Moran, A novel and essential role for FcgammaRIIa in cancer cell-induced platelet activation. Blood, 2014. 123(2): p. 249-60. 4. Battinelli, E.M., B.A. Markens, and J.E. Italiano, Jr., Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis. Blood, 2011. 118(5): p. 1359-69.

Biography

Name: Niamh Moran PhD Associate Professor in Molecular & Cellular Therapeutics

Affiliation: Royal College of Surgeons in Ireland (RCSI)

Prof. Moran has published 75 peer reviewed articles of original research over the past 15 years in the area of platelet function, clinical trials and integrin biology. She is regularly invited to speak at Gordon Research Conferences and other large international conferences, because of the novelty, innovation and application of her research in international terms. She is a strong team player and works especially with junior colleagues to help advance their careers. She is currently head of the School of Postgraduate Studies that oversees the quality of all higher degrees awarded by the Royal College of Surgeons in Ireland (RCSI)

She currently has 3 patents on novel antithrombotic drug candidates and has hosted a biotechnology mini-company (Vasogen Ireland) from 2004-2008 on the RCSI campus. Her lab have developed a novel high-throughput assay of platelet function for early detection of patients at risk of cardiovascular disease that has recieved funding from Science Foundation Ireland via a Technology Innovation Development Award. This assay may find a new niche in the diagnosis of patient favorable responses in cancer treatment.

Molecular Mechanisms of Hepatitis C Virus-Host Interactions

Tao Peng Innate immunity and human diseases, Therapeutics targeting innate immunity Director of Sino-French Hoffmann Institute, Guangzhou Medical University

Abstract

Approximately 185 million people are infected with Hepatitis C virus (HCV) worldwide. HCV causes not only severe liver problems but also extrahepatic manifestations, such as insulin resistance (IR) and type 2 diabetes mellitus (T2DM). At the molecular level, every step of HCV life cycle intimately interacts with host factors. In particular, as an enveloped positive-strand RNA virus, HCV hijacks host lipid metabolism during its life cycle, including RNA replication and assembly/release of viral particles. In this presentation, we summarize our effort in the understanding of molecular mechanisms involved in HCV-host interactions.

Biography

Tao Peng, Ph.D., Professor and Director, Sino- French Hoffmann Institute, Guangzhou Medical University. Dr. Peng received his B.Sc. degree in Biochemistry from Wuhan University, China in 1988, M.Sc. degree in Molecular Genetics from Drexel University, USA in 1994, and Ph.D. in Virology from University of Pennsylvania, USA in 1998. From 1998 to 2000, he received his postdoctoral training in the Scripps Research Institute, USA, and University of California, San Diego, USA. Afterwards, he worked for biotech companies, Immusol Inc., and Ionian Technologies, in USA as a research scientist and R&D manager from 1998 to 2004. He joined Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences in 2004 as a Principal Investigator and setup the Laboratory of Viral Immunology. Dr. Peng has received support from the “National Recruitment Program of Global Talents (the 1000 Talents Plan)”, the "Hundred Talents Program" in the Chinese Academy of Sciences, and the “Guangzhou Innovative Leading Talents Program”.

Focusing on researches related to viral infectious diseases, Dr. Peng’s group is interested in the development of antiviral and novel rapid virus detection methods. Through the understanding of virus-host interactions and the mechanisms of pathology, the goal of their research is to discover new drug targets and to develop novel cell-based/molecular assays. Currently, his lab is conducting studies on: antiviral screening and mechanism analysis; molecular mechanisms of virus entry; rapid virus detection method. Dr. Peng is serving on the Editorial Board of Antiviral Research (an official publication of the International Society for Antiviral Research, published by Elsevier), and the Editorial Board of Virologica Sinica (an international journal which aims at presenting the current basic and application research on viruses in both China and the world, published by Springer). He is the Chief Editor of “Isothermal Nucleic Acid Amplification Technology and Application” (a book designated for “isothermal nucleic acid amplification technology”, published by Science Press), and the Chief Editor of Clinical Virology (a book published by Science Press). He is the inventor of “Rapid Isothermal Nucleic Acid Detection and Amplification” (RIDA) technology. He is also the inventor of more than 10 patents/patent-applications, including the US patent “Soluble Herpesvirus Glycoprotein Complex Vaccine”.

Platelets and Innate Immunity

Dermot Cox

Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland

The conventional view of platelets is that of cell fragments that can clump together to seal damage to a blood vessel and thereby plugging any leak. However, recent data suggests that platelets also are an important part of the innate immune system. They express a number of pathogen-recognition molecules such as Toll-like receptors (TLRs). They also express directly activate or enhance platelet activation by other substances. Once activated platelets secrete their granule contents, which include pro-inflammatory cytokines, growth factors microbicidal peptides and vasoactive substances. While these have the potential to kill pathogens and recruit immune cells to the site of injury they also have the potential to induce serious illness such as disseminated intravascular coagulation, sepsis and viral haemorrhagic fever. Understanding how platelets can become the source of the problem in these conditions is important and allows us to identify novel drug targets for diseases such as sepsis.

Biography.

Dermot Cox is a senior lecturer in pharmacology in the Royal College of Surgeons in Ireland. He led an anti-platelet drug discovery team in Fujisawa pharmaceutical company in Japan for 6 years. Subsequently he developed an interest in platelet-pathogen interactions and their role in pathogenesis. His current research is on developing drugs that target these interactions.

Brief introduction of an Innovative Platelet Function Testing Analyzer and its application Xu Xin Sinnowa Medical Science & Technology Co., Ltd, Nanjing China [email protected]

Platelet is the key factor of thrombosis [1] and anti-platelet medication is the “Corner Stone” in thrombosis diseases prophylaxis and therapy [2]. Since 2002, a lot of clinical observation and research confirms that anti-platelet medicine has a great individual difference, recurrence of thrombosis or bleeding was very often found following standard prescription [2]. So personalized prescription of anti-platelet medicine is very necessary in thrombosis diseases prophylaxis and therapy and PLT function test is become very important. Unfortunately although many different type analyzers were developed and used for PLT function test in the passed 60 years. But almost all of them with the common problems: high CV%, complicated operation, time costly and poor harmonization or standardization [4-7] .A more convenient, more standardization, more accurate and faster PLT function analyzer is urgently needed. The author invents an innovative platelet function testing method and developed the new PLT function analyzer (PL-11). The new method is named “sequential platelet counting method, SPCM”, which tests the PLT function by automatically counting the PLT number in the sample sequentially and comparing the PLT numbers before and after addition of platelet agonist. The analyzer directly tests fresh whole blood (sodium citrate) sample, 5-7 minutes per test, only 250μL per test [8-13]. Moreover, the analyzer provides comprehensive report including PLT numbers, MPV, et al, and with its QC system which makes the test result more accurate and more believable. Several evaluation studies were published including the comparing study with LTA and with Verifynow. The MAR% CV is ≤ 7%, the correlation are: r=0.614, p<0.01(PL-11 VS LTA); r=0.829, p<0.01(PL-11 VS VerifyNow ) [14]. The analyzers now are used in about 100 labs in china. Figure 1. Comparing study of 4 types of PLT function analyzers provided by Prof. Yulong Cong

Reference:

[1] Michelson, A. D. Platelets 2nd (Elsevier/Academic Press, San Diego, 2007). [2] Patrono, C., Baigent, C., Hirsh, J. & Roth, G.Antiplatelet drugs. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 133, S199–S233 (2008). [3] Bal Dit Sollier C, Berge N, Boval B, et al. Functional variability of platelet response to clopidogrel correlates with P2Y(12) receptor occupancy[J]. Thromb Haemost, 2009, 101(1):116-122. [4] Matetzky S, Fefer P, Shenkman B, et al. Effectiveness of reloading to overcome clopidogrel nonresponsiveness in patients with acute myocardial infarction [J]. Am J Cardiol, 2008, 102(5): 524-529. [5] Marie Lordkipanidze, Chantal Pharand, Erick Schampaert, et al. Evaluation of the platelet count drop method for assessment of platelet function in comparison with “gold standard” light transmission aggregometry [J]. Thrombosis Research, 2009, 124(4): 418-422. [6] Breddin HK. Can platelet aggregometry be standardized.[J] Platelets, 2005,16(3-4):151- 158. [7] LinnemannB, Schwonberg J, Mani H, et al. Standardization of light transmittance aggregometry for monitoring antiplatelet therapy: an adjustment for platelet count is not necessary[J]. J Thromb Haemost, 2008, 6(4):677-683. [8] XL Wu, J Li, CB Wang et al. Evaluation on Platelet Function testing with whole blood on PL-11 and its clinical significance. [J] J of Clinical Lab. 2013, Vol. 2, No. 2, 355-359. [9] Junwei Ren, Jie Bai, Yulong Cong et al. Study on Platelet Aggregation Function testing Method and Parameters. [10] Evaluation on a new Platelet Aggregation Testing Method and the instrument and its clinical application. [J] Journal of Experimental Hematology. 2013:21(3):674-677. [11] YT Zhang, YM Zhao, SD Ji et al. Performance on PL-11 to Platelet Aggregation Function testing. [J] Chin J Lab Med, December 2012, Vol.35, No.12: 1139-1141. [12] Zhao Yiming, Zhang Youtao, Ruan Changgeng ,et a1.Evaluation study of a new, direct whole blood platelet function assay and its applications. ISTH, June 29 - July 4, 2013 Amsterdam, Netherlands. [13] Junwei Ren, Jie Guan, Yuan Zhu, Jie Bai, Yulong Cong. An innovative Platelet Aggregation Function Testing instrument and comparison study on other instruments. [14] Jie Guan1, Yulong Cong1, Junwei Ren2 Comparison between a new platelet count drop method PL-11, light transmission aggregometry, VerifyNow aspirin system and thromboelastography for monitoring short-term aspirin effects in healthy individuals, [J] platelets.

Biography Given Name: Xin Surname: Xu Affiliation SINNOWA MEDICAL SCIENCE & TECHNOLOGY CO., LTD

Microbiologist and Prof. of Biomedical Engineering; Focused on the research and develop the technologies and products in vitro diagnostic since 1995, undertaken 4 projects sponsored by Ministry of Science and Technology of China and winner of a couple of awards; one of the main inventor of Sequential Platelet Counting Method for Platelet Function Testing technology; owner of 3 invention Patents of China.

Sodium Tanshinone IIA Sulfonate (STS) on Pulmonary Hypertension (PH): From Basic Research to Clinical Trial Jian Wang (Internal Medicine (respiratory disease) , Director ,Department of Scientific Research,Guangzhou Medical University )

Pulmonary hypertension (PH) is a lethal disease with no cure currently available. Danshen is widely used in Chinese clinics in treating various cardiovascular diseases. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of tanshinone IIA isolated as the major active component from Danshen. By using rat PH models of both chronically hypoxia- induced (CHPH) and monocrotaline-induced (MCT-PH), we observed that STS treatment (intraperitoneally, 10 mg/kg/d) significantly attenuated the PH pathogenesis, featured as normalizing the 1) elevated right ventricle systolic pressure (RVSP); 2) aggregated right ventricle hypotrophy (RVH); and 3) increased distal pulmonary arterial remodeling. In mechanism, STS attenuated the PH development by targeting the intracellular calcium homeostasis, mainly affecting the store-operated calcium entry (SOCE) and the related channel components, the canonical transient receptor potential (TRPC1 and TRPC6). In cultured pulmonary arterial smooth muscle cells (PASMCs), STS (0-25 μM) dose- dependently 1) inhibited hypoxia-induced proliferation and migration; 2) suppressed the 2+ basal intracellular calcium concentration ([Ca ]i), SOCE and TRPC expression. Moreover, we further performed a pilot clinical study enrolling five hospitalized patients, who suffered from various types of serious PH without getting sufficient benefits from sildenafil treatment (20 mg, t.i.d) for at least three months. After the treatment, all patients exhibited impressive outcome such like: 1) improved exercise capacity (6MWD); 2) reduced Borg dyspnea score; and 3) reduced the WHO functional class of PH. Both basic and clinical evidence indicated STS exhibits remarkable beneficiary effects on treating PH, which deserves further study in the future research.

Biography:

Jian Wang is a professor of the State Key Laboratory of Respiratory Disease, Guangzhou Medical University. Dr. Wang is awarded as the Pearl River Scholarship Professor, the team leader of the Yangtze River Innovation Program of Ministry of Education of China, the first and second instance expert of the National Natural Science Foundation of China. Dr. Wang is an Assistant Professor of the Division of Pulmonary & Critical Care Medicine of Johns Hopkins University and the academic leader of the Pulmonary Vascular Disease Study Group of Guangzhou Medical University. Dr. Wang is a member of the American Thoracic Society (ATS), the ATS Pulmonary Circulation Academic Committee, the American Heart Association and the American Physiology

Society. He is also editorial board member of Pulmonary Circulation and Chinese Journal of Tuberculosis and Respiratory Disease. Dr. Wang has won the Young Scientist Award of the Respiratory Branch of American Physiological Society in 2006, and the Outstanding Scientist Award of the Basic Research Medicine of Johns Hopkins University twice in 2003 and 2008.In parallel, Dr. Wang also won the first grade of the Guangdong Province Science and Technology Progress Award and the second grade of the Guangzhou Municipal Science and Technology Progress Award. During the past years, Dr. Wang has published over 60 research articles in high impact journals like Lancet and Circulation Research. The overall impact factor has reached over 290 and the overall citation (except self-citation) has reached 2800. At the same time, he advised as mentor of 12 master candidates, 12 PhD candidates and 2 post-doctoral research fellow for their research projects and helped them to successfully graduate. Nine of these students have been awarded the scholarship of either the China Scholarship Council or the Guangzhou Government Program and pursued their research in top universities like Johns Hopkins University and Harvard University as exchange visitors. Dr. Wang has assumed the research projects at all levels of national, provincial and municipal for 16 times, including 4 National Natural Science Foundation of China, 1 International Cooperation Project, 1 "973 Project" sub topic and 1 Yangtze River Innovation Team Project of the Ministry of Education. He owns 16 national patents, including 7 national invention patents. Currently, Dr. Wang's research interest focused on: 1) the role of abnormal pulmonary vascular morphology and function (such as chronic obstructive pulmonary disease) on the development of lung injury; 2) the molecular regulative mechanisms of the calcium channels under the pathogenesis of pulmonary hypertension; 3) the relationship between nicotine and pulmonary hypertension; 4) determine the mechanism of chronic hypoxia-induced pulmonary hypertension and evaluate the usage of Traditional Chinese Medicine on the prevention and treatment of pulmonary hypertension.

The Role of Mitochondrial Uncoupling Proteins (UCP’s) in Thymocyte/T-Cell Development and Function. Richard K. Porter

School of Biochemistry and Immunology, Trinity Biomedical Science Institute (TBSI), Trinity College Dublin.

The thymus is the site of thymocyte maturation and development. After a rigorous self and non-self antigenic selection process, naïve T-cells are released from the thymus to the circulation and peripheral lymph sites. We have demonstrated that specific members the mitochondrial inner membrane transporter family, namely the uncoupling proteins (UCP’s), are present in thymocytes/T-cells, and that the absence of these transporters effect T-cell development and function. My research has direct relevance to understanding immune cell function and modulation and has clinical implications for cancer and autoimmune diseases.

Figure: Identification of UCP1 in thmyocytes

THY-1 Mitochondria UCP-1 Merge

C5 C57 BL/7B

6 L/ WI6 LDTU CP YPE 1- /-

Reference: (including full name of article) Kieran J. Clarke, Audrey M. Carroll, Gemma O’Brien, Richard K. Porter (2014) Detection of UCP1 Protein and Measurements of Dependent GDP-Sensitive Proton Leak in Non-Phosphorylating Thymus Mitochondria. Mitochondrial Regulation, Methods in Molecular Biology, vol. 1241, © Springer

Biography Richard K. Porter Trinity College Dublin, Ireland

Short biography Education and Qualifications: B.A. (Moderatorship) in Biochemistry, Trinity College Dublin (1986); Ph.D. Biochemistry, Trinity College Dublin (1991); Employment: Elected Head of Biochemistry (2011 to present); Associate Professor in School of Biochemistry and Immunology (2011); Senior Lecturer in School of Biochemistry and Immunology (2006); Permanent Lecturer in Biochemistry, Trinity College Dublin (2000-present); Lecturer in Biochemistry, Trinity College Dublin (1997-2000); Health

Research Board of Ireland Post-doctoral Fellow (1994-1997) based in The Department of Biochemistry, University of Dublin, Trinity College Dublin; Postdoctoral Researcher, Department of Biochemistry, University of Cambridge, UK. (1991-1994); Honours and Awards: Provost’s Teaching Award Commendation (2014); Fellow of Trinity College Dublin (2007); Professional Achievements and Responsibilities: Current Editor with Biochimica Biophysica Acta Bioenergetics, Elsevier Publications. Guest editor for: (1) Biochemical Society Transactions, Portland Press; (2) Biochimica Biophysica Acta Bioenergetics (Special issue), Elsevier Publications. (3) EBEC Short Reports; Elsevier Publications. Scientific advisor to Iperboreal Pharma Pescara Italy. Member of the Nominating Committee for the International Union of Biochemists and Molecular Biologists (IUBMB). Member of the European Bioenergetics Committee. Treasurer of the Irish Area Section of the Biochemical Society (2010- 2013).

Epilepsy Genetics: Generalized Epilepsy VersusPartial Epilepsy

Dr Wei-Ping Liao Institute of Neuroscience of Guangzhou Medical University& Key Laboratory ofNeurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China

It is well known that generalized epilepsy differs from partial epilepsy in many clinical and electroencephalographical aspects; and there are also cases with features of both generalized and partial epilepsies. Recent studies have demonstrated their differences in genetics, which provided an inside of the molecular basis and underlying mechanism of epilepsy. There are certain genes that tend to associate with generalized epilepsies. As an example, absence seizures typically occur in generalized epilepsies. Anatomically, corticothalamic circuit is the structure basis for generation of absence seizure and the 3.0 Hz spike-and-wave discharge. Molecular changes that lead to increased excitability or decreased inhibition in the corticothalamic circuit may cause absence seizures and generalized epilepsy, such as mutations in GABA receptor genes and calcium channel genes. On the other hand, there are several genes that are more or less exclusively associated withpartial epilepsies. For instances, mutations in acetylcholine receptor genes are associated with nocturnal frontal lobe epilepsy; abnormalities in several types of potassiumchannels may cause temporal lobe epilepsy. Regional expression of channels was considered as one of the explanations for the pathogenesis of partial epilepsy. Sodium channel gene SCN1A is the most relevant epilepsy gene. Mutations in SCN1A generate phenotypes from mild generalized epilepsy with febrile seizures plus, to the intermediate partial epilepsy with febrile seizures plus, and then the severe form of Dravet syndrome that revealing features of both generalized and partial epilepsies. Correlations between the phenotype, functional defect, and genotype of SCN1A have been disclosed, which provides an example to show the distinction and co-existence of generalized epilepsy and partial epilepsy. Clinically, generalized epilepsy aggravated by GABA receptor acting antiepileptic drugs (AEDs) has been recognized. Our recent studies have shown that sodium channel blocker AEDs aggravate seizures in patients with partial epilepsy and loss-of-function of Nav1.1. Therefore, understanding the molecular distinction between generalized epilepsy and partial epilepsy will help physicians in management of epilepsy.

Biography of Dr. Wei-Ping Liao

Dr Wei-Ping Liao is a Professor of Neurology at the Second Affiliated Hospital of Guangzhou Medical University in China. He is now a vice president of China Association Against Epilepsy (CAAE) and the associate editor of SEIZURE, European Journal of Epilepsy.

He graduated from HunanMedicalUniversity in 1983 and subsequently trained in Neurology until 1986. He obtained further training in Epileptology in the National Epilepsy Center of Japan between 1988 to1989. Now, he directs the Institute of Neuroscience and Epilepsy Unit, which provides a range of services for people with neurological disorders and epilepsies. He is also the director of the Key Laboratory ofNeurogenetics and Channelopathies of Guangdong Province and the Ministry of Education ofChina, leads a team in basic studies on epilepsy. His research interests include genetics, physiological and pathological basis of epilepsy. He has published many papers in recent years. He also served as an editorial board member of Epilepsia, and reviewer for many journals.

He is one of the active leaders of the AsianEpilepsy Academy (ASEPA). He has organized many domestic and international epilepsy conferences in recent years. He was awarded Ambassador for Epilepsy in 2011 for his contributions in epileptology.

Institute of Neuroscience, the Second Affiliated Hospital of Guangzhou Medical University, Chang-gang-dong Road 250, Guangzhou 510260, P.R. China. Tel +86-20-34152625, Mobile +18926298169, Fax +86-20-34153378. e-mail:[email protected];[email protected]

Association of selenium status and selenoprotein gene variation with colorectal cancer risk Hughes DJ. 1; Fedirko V. 2; Méplan C. 3; Schomburg L. 4; Riboli E. 5; Hesketh J. 3, Jenab M. (on behalf of EPIC Group) 6

1 Centre for Systems Medicine, Department of Physiology & Department of Epidemiology and Public Health Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland 2 Rollins School of Public Health, Emory University, Atlanta GA, USA 3 Institute of Cell and Molecular Biosciences, University of Newcastle, UK 4 Institute for Experimental Endocrinology, University Medical School Berlin, Germany 5 School of Public Health, Imperial College London, UK 6 Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France

Background and objectives: Suboptimal intakes of the micronutrient selenium (Se) are found in many parts of Europe and may contribute to colorectal cancer (CRC) development. Se exerts its biological roles through 25 selenoproteins involved in cell protection from oxidative stress, redox control and inflammatory response. We are currently using a case- control study of 1478 CRC cases and 1478 matched controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to assess both the association of Se status and selenoprotein genotype with CRC risk, and their interaction in disease risk modification. Methods: Serum levels of Se (total reflection X-ray fluorescence) and SePP (immunoluminometric sandwich assay) were measured in samples available from 966 of the cases and 966 controls. Multivariable incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Tagging SNPs (N=760) in the Se pathway (all 25 selenoprotein genes plus 91 genes in pathways sensitive to Se intake) were assayed by Illumina Goldengate genotyping in DNA samples available for all 1478 cases and 1478 controls. Results: Respective mean Se and SePP levels were 84.0 μg/L and 4.3 mg/L in cases and 85.6 μg/L and 4.4 mg/L in controls. Higher Se concentrations were associated with a non- significant lower CRC risk (IRR = 0.92, 95%CI: 0.82-1.03 per 25 μg/L increase)1. However, sub-group analyses by sex showed a statistically significant association for women (IRR =

0.83, 95%CI: 0.70-0.97 per 25 μg/L Se increase; Ptrend = 0.032) but not for men. Higher SePP concentrations were inversely associated with CRC risk (IRR = 0.89, 95%CI: 0.82-0.98 per

0.806 mg/L increase; Ptrend = 0.009) with the association more apparent in women (IRR = 0.82, 95%CI: 0.72-0.94 per 0.806 mg/L increase; Ptrend = 0.004) than men (IRR = 0.98, 95%CI: 0.86-1.12 per 0.806 mg/L increase; Ptrend = 0.485). While all of the Se pathway genotypes are currently being analyzed, 22 SNPs in 11 of the 25 selenoprotein genes were associated with an altered CRC risk. Conclusions: The findings from this large prospective nested case-control study indicate that Se status is suboptimal in many Europeans and suggest an inverse association between CRC risk and higher serum Se status, which is more evident in women. Common genetic variation

in the selenoprotein gene pathway may affect CRC development risk and also is likely to modify risk associated with Se status.

Reference: (including full name of article) 1. Hughes DJ, Fedirko V, Jenab M, Schomburg L, Méplan C, Freisling H, Bueno de Mesquita HB, Hybsier S, Becker NP, Czuban M, Tjønneland A, Outzen M, Boutron- Ruault MC, Racine A, Bastide N, Kühn T, Kaaks R, Trichopoulos D, Trichopoulou A, Lagiou P, Panico S, Peeters PH, Weiderpass E, Skeie G, Dagrun E, Chirlaque MD, Sánchez MJ, Ardanaz E, Ljuslinder I, Wennberg M, Bradbury KE, Vineis P, Naccarati A, Palli D, Boeing H, Overvad K, Dorronsoro M, Jakszyn P, Cross AJ, Ramón Quirós J, Stepien M, Kong SY, Duarte-Salles T, Riboli E, Hesketh JE. Selenium Status is Associated with Colorectal Cancer risk in the European Prospective Investigation of Cancer and Nutrition Cohort. Int J Cancer. 2015 Mar 1;136(5):1149-61. PMID: 25042282

Biography Name: David Hughes Affiliation: Centre for Systems Medicine, Department of Physiology & Department of Epidemiology and Public Health Medicine, Royal College of Surgeons in Ireland, Dublin 2, Ireland) Dr David Hughes is one of the P.I.’s in the Royal College of Surgeons in Ireland (RCSI) at the Centre for Systems Medicine institute, and a lecturer in epidemiology and public health at the RCSI, which he joined in October 2011. His current research includes cancer epidemiology (genetic, nutritional, and microbial) and genetic cancer biomarkers. He has published >40 international peer reviewed articles, including recent articles in the New England Journal of Medicine and the International Journal of Cancer, and is a Steering Committee member of the European Prospective Investigation into Cancer and Nutrition (EPIC) CRC nested cohort. David received his B.Sc. Biochemistry degree from the University of Leeds in 1990. Afterwards, he worked as a research assistant to Prof John Hardy at St Mary’s Medical School, Imperial College London (genetics of Alzheimer Disease, AD). During this time, the group published in Nature that mutations in the APP gene can cause AD, the first gene linked with this disorder. In 1996 he obtained his PhD in the Department of Medical Genetics, Queen’s University Belfast, Northern Ireland on the mutation characterization and haplotype analysis of the CFTR gene, variants of which may cause cystic fibrosis (CF). Published data from this work have been used since for CF genetic testing in Ireland and also included a novel use of microsatellite haplotype directed mutation testing for rare CF variants. Dr Hughes’s first postdoctoral positions involved a short fellowship studying atypical cases of CF at the Institute for Human Genetics in Hanover Medical School, Germany and then a two-year post (1998-2000) to begin functional genomic projects on the model nematode, C. elegans as part of the post-sequencing efforts of the C. elegans genome in the group of Prof John Sulston at the Sanger Institute, Cambridge, England. From 2000-2006 he was employed as a scientist at the World Health Organization’s cancer research headquarters (the International Agency for Research on Cancer in Lyon, France). His work there primarily concerned the genetic epidemiology of breast cancer (BC). As part of this work, the first confirmed genetic modifiers of the BRCA genes and BC susceptibility in general were located (including papers in Nature Genetics and JNCI). Dr Hughes returned to Ireland in 2007 where he worked as a research fellow at Trinity College Dublin until his move to the RCSI. He was instrumental is setting up the CRC genetic research projects at the AMNCH Trinity site and was a team member for the first pilot immunochemical FOBT CRC screening program in Ireland.

Pharmacogenomics research in epilepsy: finding genetic predictors of clinical response to AEDs

Mark McCormack*, Hongsheng Gui, Doug Speed, the International League Against Epilepsy Consortium on Complex Epilepsies, the EPIPGX Consortium, Stacey S. Cherny, Chantal Depondt, Erin Heinzen, David B. Goldstein, Slave Petrovski, Patrick Kwan, Terence J O’Brien, Larry Baum, Sanjay Sisodiya, Norman Delanty and Gianpiero L. Cavalleri

*Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland

Main Text:

Epilepsy is typically treated using antiepileptic drugs (AEDs) however there is considerable heterogeneity of response among patients. Up to 30% of patients are refractory to existing medication. Information guiding clinicians on the most effective drug and dose for individual patients is lacking. Further, all AEDs have associated adverse reactions (ADRs), some of which are severe and life-threatening such as the varying hypersensitivity reactions observed in a proportion of patients using carbamazepine, lamotrigine and phenytoin. In fact, the major success stories in epilepsy pharmacogenetics have been the identification of HLA markers associated with cutaneous reactions to carbamazepine. There is considerable interest also in finding genetic markers of both common and rare ADRs such as vigabatrin-associated visual field loss and weight gain with sodium valproate, examples of major limiting factors in the use of potentially beneficial AEDs. With the availability of high-density GWAS panels and a move towards multi-centre collaboration to provide standardized phenotyping in large cohorts, as is the goal of the EpiPGX Consortium, there is now the necessary power to investigate drug-resistance, drug-responsiveness and a catalogue of known ADRs in patients with epilepsy. This presentation will describe the recent and ongoing efforts in epilepsy pharmacogenomics to provide genome-based predictive biomarkers for use in routine clinical practice.

Reference: (including full name of article) McCormack M, et al N Engl J Med. 2011 Mar 24;364(12):1134-43. Cavalleri GL, McCormack M, Alhusaini S, Chaila E, Delanty N. Pharmacogenomics and epilepsy: the road ahead. Pharmacogenomics. 2011 Oct;12(10):1429-47. McCormack M et al, Genome-wide mapping for clinically relevant predictors of lamotrigine and phenytoin-induced hypersensitivity reactions. Pharmacogenomics. 2012 Mar;13(4):399- 405.

Biography Name: Mark McCormack Affiliation: Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland

My primary research interest is the genetics of epilepsy, with particular interest in the identification of pharmacogenomics markers of response to anti-epileptic drug (AED) treatment through GWAS and next-generation sequencing. Working under the supervision of Prof. Norman Delanty (Consultant Neurologist, Beaumont Hospital) and Dr. Gianpiero Cavalleri (Geneticist, RCSI), our research group identified HLA-A*3101 as a predictive marker for carbamazepine-induced hypersensitivity in European epilepsy patients, a common adverse reaction that can range from a mild skin irritation to the potentially fatal Stevens-Johnson Syndrome. For this work, I was awarded the title of RCSI Researcher of the Year 2011, the John Kirker Prize for Epilepsy Research by the Irish Neurological Association and the Lodewijk Sandkuijl Award for Complex Genetics at the European Society of Human Genetics. Our research group in RCSI is a key site linking two of the world’s largest epilepsy genetics consortia, namely Epi4K (which concerns inherited epileptic disorders) and EpiPGX (which focuses on patient response to AEDs). Through EPIPGX we have collected extensive phenotype information on thousands of European epilepsy patients. We are particularly interested in extreme phenotypes such as early drug responders, refractory patients and patients with extreme adverse reactions. Our research group also aims to apply targeted and whole exome sequencing as a clinical diagnostic tool for identifying and characterizing single gene disorders in Irish sporadic epilepsy patients with unknown cause. We aim to be the first group in Ireland to translate next-generation sequencing results to a clinical setting to help guide diagnosis in epilepsy.

Links between COPD and Lung cancer

Jiachun Lu (Epidemiology, Dean of School of International Education,Guangzhou Medical University)

Abstract: Chronic obstructive pulmonary disease (COPD) and lung cancer are the most striking lung diseases with high and increasing morbidity and mortality worldwide. COPD and lung cancer are closely related as that COPD patients suffer four-fold higher lung cancer risk than the general population. Moreover, 40-70% of lung cancer patients complicate with COPD. It is well recognized that these two diseases share some pivotal pathologic mechanisms such as chronic inflammation, DNA damages and epithelial-to-mesenchymal transition (EMT), etc. Revealing the shared factors of COPD and lung cancer would not only help both diseases prevention but also deepen our knowledge about their etiological link.

Biography: Dr. Jiachun Lu, MD., Ph. D., Professor of epidemiology, Principal Investigator of State Key Laboratory of Respiratory Disease, Academic Committee Member, Guangzhou Medical University, China. He has been on faculty since 1994, and trained in the University of Texas, MD Anderson Cancer Center as a postdoctoral fellow during 2005 to 2007. Dr. Lu is involved in many studies investigating the molecular epidemiology of lung cancer, COPD and other respiratory diseases with particular focus on its frequency, risk factors and genetic susceptibility in large populations. He also involved in the epidemiology of other cancers. In his lab, with both traditional and molecular epidemiology, they conducted research based on the blueprint of “Find the associations between exposures and disease in population studies → Validate the association with functional assays in laboratory → Guide the prevention of disease in population”, funded by more than seven projects of National Nature Science Foundation of China. Dr. Lu has published more than 80 research articles in SCI journals, including corresponse author in Am J Respir Crit Care Med., Am J Hum Genet., Hum Mol Genet., Human Mutat., Hum Genet., Carcinogenesis, Mol Carcinog., Int J Cancer, and co-author in Nat Genet., Lancet, BMJ, PLoS Genet., Gastroenterology, and Cancer Res., with >3900 citations, >550 impact factor scores and a 24 H-index score.

Role of Toll-like receptors in Osteoarthritis

Ashwini Maratha*, JVS Vidyasagar#, M. Lakkireddy# and Sinéad M. Miggin*

*Immune Signalling Laboratory, Institute of Immunology and Department of Biology, National University of Ireland Maynooth, Maynooth, Ireland. #Aware Global Hospital, LB Nagar, Sagar Road, Hyderabad-500035

Osteoarthritis (OA) is associated with low-grade synovitis and inflammation which may be associated with Toll-like receptor (TLR) activation. The aim of this study was to determine the key TLRs in the synovium and explore their roles in the activation of fibroblast-like synoviocytes (FLSs) and OA synovial explant tissue.

Using primary normal, OA and rheumatoid arthritis (RA) FLS as models, TLR and cytokine expression was detected by performing real-time PCR following stimulation with TLR ligands. Also, TLR ligand-induced proinflammatory cytokine, chemokine and MMP production were measured by Meso Scale Ultrasensitive ELISA System. Next, ex vivo FLS from patients with early and late OA and OA synovial membrane explant tissues were used as models to detect TLR ligand-induced proinflammatory cytokine and chemokine production by Meso Scale Ultrasensitive ELISA System.

Significant time and ligand dependent upregulation of TLR2, TLR3, TLR4, TLR6 and TLR7, but not other TLRs, was evident in OA-FLS when compared to N-FLS. Significant time and ligand dependent upregulation of TLR2, TLR3, TLR4, TLR5, TLR8 and TLR9 was evident in RA FLS when compared to N-FLS. OA-FLS spontaneously secreted IL-6, IFN-β and RANTES and secreted IFN-β and RANTES in a TLR3 and TLR7 dependent manner. Also, OA-FLS secreted IL-1β, TNFα and IL-6 and IL-15 regulated by TLR3, and to a lesser extent, TLR7. Also, IFN-β induced the production of RANTES, IL-6, TNFα and IL-1β. Using early and late ex vivo OA-FLS, predominant TLR3-mediated production of IL-6, IL-8, IFN-β, IL- 1β, TNFα and RANTES was observed. Furthermore, OA synovial tissue explants were found to spontaneously secrete IL-6, IL-8, IL-1β, TNFα, IFN-β and RANTES and predominant TLR3-mediated production of IL-6, IL-8, IL-1β, TNFα, IFN-β and RANTES was detected.

Kindly supported by the Health Research Board of Ireland.

Biography Name: Dr Sinéad Miggin Affiliation: Department of Biology, Maynooth University, Co. Kildare, Ireland

Email: [email protected] Web: www.maynoothuniversity.ie/biology/

Dr Sinéad Miggin graduated in Toxicology from Athlone Institute of Technology in 1994. She was awarded a PhD in Biochemistry which was undertaken at the Conway Institute, University College Dublin in 2000. She subsequently undertook a Postdoctoral Fellowship in Inflammation research at the Conway Institute (2000-2002) followed by a Senior Postdoctoral Fellowship at the Department of Biochemistry and Immunology, Trinity College Dublin, Ireland (2002-2006). She was appointed Lecturer in Immunology at the National University of Ireland Maynooth in 2006.

Dr Miggin is interested in exploring the molecular mechanisms involved in regulating the inflammatory response through the Toll-like receptors (TLRs). To this end, her group employs cutting edge proteomics technologies to identify novel modulators of TLR signalling and inflammatory processes. Her group is particularly interested in understanding the inflammatory responses linked with Osteoarthritis and Type II Diabetes.

Oncoproteomics - preparing for the challenges ahead

Paul Dowling Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland e-mail: [email protected] Tel: 0035317086368

Abstract Oncoproteomics, the application of proteomics technologies in oncology, particularly their structures and functions, has evolved quiet considerably over the past decade or so. Modern proteomics workflows and platforms have considerably added to our ability to dig deeper into the proteome and have allowed researchers to analyse a new protein population previously found to be inaccessible. Proteomics is broadly broken down into two areas. The first area is focused on quantifying the expression levels of proteins between different groups, for instance looking for biomarkers from patients with a particular cancer that will allow for early detection/monitoring/treatment of that disease. The second area focuses on functional proteomics, generating information on where the proteins are localized to, what other proteins they interact with and if they contain any post-translational modifications that are important to their function. Answers to these questions will culminate in the identification of many disease-related biomarkers and potential new drug targets (1-4).

Figure

Immunohistochemistry analysis of protein hnRNPA2B1 showed elevated levels of staining in malignant tissue. Knockdown of hnRNPA2B1 demonstrated its role in invasion and migration. References

1. Dowling P, Hughes DJ, Larkin AM, Meiller J, Henry M, Meleady P, Lynch V, Pardini B, Naccarati A, Levy M, Vodicka P, Neary P, Clynes M. Elevated levels of 14-3-3 proteins, serotonin, gamma enolase and pyruvate kinase identified in clinical samples from patients diagnosed with colorectal cancer. Clin Chim Acta. 2014 2. Dowling P, Pollard D, Larkin A, Henry M, Meleady P, Gately K, O'Byrne K, Barr MP, Lynch V, Ballot J, Crown J, Moriarty M, O'Brien E, Morgan R, Clynes M. Abnormal levels of heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in tumour tissue and blood samples from patients diagnosed with lung cancer. Mol Biosyst. 2014 3. Dowling P, Hayes C, Ting KR, Hameed A, Meiller J, Mitsiades C, Anderson KC, Clynes M, Clarke C, Richardson P, O'Gorman P. Identification of proteins found to be significantly altered when comparing the serum proteome from Multiple Myeloma patients with varying degrees of bone disease. BMC Genomics. 2014; 15:904. 4. Dowling P, Henry M, Meleady P, Clarke C, Gately K, O’Byrne K, Connolly E, Lynch V, Ballot J, Gullo G, Crown J, Moriarty M, Clynes M. Metabolomic and proteomic analysis of breast cancer patient samples suggests that glutamate and 12-HETE in combination with CA15-3 may be useful biomarkers reflecting tumour burden. Metabolomics 2014

Name: Paul Dowling Affiliation: Department of Biology, Maynooth University, Maynooth, Co. Kildare, Ireland

The position of Paul Dowling as leader of the Clinical Proteomics laboratory at Maynooth University involves identifying proteins involved in human disease and to understand how their expression, structure and function cause illness. We have been part of a group of proteomics researchers that has successfully established a very competitive lab, producing world-class results that are continually published in some of the best proteomics journals. Strategically, proteomics is a very important area as it is still a relatively new science, and researchers have only scraped the surface as regards how powerful proteomics will become over the coming years. Vital to the development of a successful proteomics facility is close connections and collaborations with clinicians and others researchers. In this regard, our collaboration with Dr Peter O’Gorman from the Mater Hospital has resulted in the assembly a team of dedicated clinical proteomics researchers, composed of both MD and PhD students, working both in Ireland and the Dana Farber Cancer Institute, USA, investigation companion biomarkers and molecular mechanisms associated with drug resistance in Multiple Myeloma. We are also very active in lung and breast cancer research programmes in collaboration with Dr Ross Morgan, Beaumont Hospital and Prof John Crown, St Vincents Hospital. We would see these research programmes affording the opportunity, stability and resources to amalgamate many of the interdependent steps necessary for cancer research to progress successfully from the lab into routine clinical practice.

Target swith from DNA to Protein makes platinum a more attractive anti-cancer agent

Jinbao Liu (Pathophysiology, Dean, Graduate School, Guangzhou Medical University)

ABSTRACT Proteasome inhibition is a novel and effective therapeutic approach that is being investigated in multiple cancer including non-small cell and small cell lung cancer. Our previous work and other reports suggested that metal complexes especially copper inhibit tumor proteasome. However, the involved molecular mechanism has not been completely defined. In our current work, we show that (i) synthetic and well-characterized complex of platinum (PtPT) inhibits the ubiquitin-proteasome function; (ii) PtPT inhibits 19S proteasome DUBs rather than other cellular DUBs or 20S proteasome peptidases; (iii) PtPT selectively induces cytotoxicity in multiple cancer cell lines and cell apoptosis mediated by caspase activation in cancer cells; (iii) PtPT induces cytotoxicity and proteasome inhibition in cancer cells from actue myeloid leukemia patients;(iv) contrast to cisplatin, a well-known platinum-containing anti-cancer agent, PtPT only targets deubiquitinase proteins rather than DNA. These results confirm that a novel platinum complex is a potent proteasomal DUB inhibitor and can partially overcome cisplatin resistance in cancer cells, with promising clinical significance in cancer treatment.

Biography:

Jinbao Liu has studied/worked in biomedicine for 33 years in China (2 years in U.S.A). He was appointed Lecturer in 2001, promoted to Associate Professor in 1998, and became full Professor in 2003 and Dean of the Graduate School of GMU in 1999. Most of his research projects funded by NSFC and National 863 Hi-Tech grants focus on protein modification and degradation in cancer and related diseases. His current research is on developing proteasome and deubiquitinase inhibitors that target for cancer therapy.

From cancer cell biology and systems biology to systems medicine Markus Rehm, PhD Lecturer in Physiology and Biophysics Centre for Systems Medicine, Department of Physiology and Medical Physics Royal College of Surgeons in Ireland Phone: +353-1-402-8563 E-mail: [email protected]

Novel treatment options for personalised, patient-tailored anti-cancer therapies can now be explored or developed through newly emerging and innovative research disciplines that go significantly beyond the current state-of-the-art, such as translational cancer systems biology and cancer systems medicine. At the RCSI Centre for Systems Medicine (CSM), we aim to obtain an unmatched depth of molecular, mechanistic and systems-level disease understanding in order to develop predictive mathematical models for disease prognosis and treatment personalisation. In this seminar, I will provide an overview on methodological approaches developed and employed at the CSM and present our recent achievements in proteomics-based cancer systems medicine.

Selected recent references: Ichim G, Lopez J, Ahmed S, Muthalagu N, Giampazolias E, Delgado ME, Parsons MJ, von de Kooij B, Bouchier-Hayes L, Chalmers AJ, Borst J, Oberst A, Rehm M, Murphy DJ, Tait SW. – Limited mitochondrial permeabilisation causes DNA-damage and genomic instability in the absence of cell death. Mol Cell. 2015 in print Wang S, Xia P, Rehm M, Fan Z. – Autophagy and cell reprogramming. Cell Mol Life Sci. 2015 in print. Charles EM, Rehm M. – Key regulators of apoptosis execution as biomarker candidates in melanoma. Mol Cell Oncol. 2014 Dec23;1:3, e964037 Würstle ML, Zink E, Prehn JH, Rehm M. - From Computational Modelling of the Intrinsic Apoptosis Pathway to a Systems-Based Analysis of Chemotherapy Resistance: Achievements, Perspectives and Challenges in Systems Medicine. Cell Death Dis. 2014 May 29;5:e1258 Passante E, Würstle ML, Hellwig CT, Leverkus M, Rehm M. - Systems analysis of apoptosis protein expression allows the case-specific prediction of cell death responsiveness of melanoma cells. Cell Death Differ. 2013 Nov;20(11):1521-31 Hector S, Rehm M, Schmid J, Kehoe J, McCawley N, Dicker P, Murray F, McNamara D, Kay EW, Concannon CG, Huber HJ, Prehn JH. - Clinical application of a systems model of apoptosis execution for the prediction of colorectal cancer therapy responses and personalisation of therapy. Gut. 2012 May;61(5):725-33. Epub 2011 Nov 14

Biography Markus Rehm, PhD; Lecturer in Physiology and Biophysics Centre for Systems Medicine, Department of Physiology and Medical Physics Royal College of Surgeons in Ireland E-mail: [email protected]

Markus Rehm leads an independent research group within the Department of Physiology and Medical Physics since 2005 and was appointed as a tenured Research Lecturer in Physiology and Biophysics in 2007. Since 2011, Dr Rehm serves in the Executive Council of the RCSI Centre for Systems Medicine. Dr Rehm leads translational systems biological research projects and coordinates national and international research collaborations in the area of cancer systems medicine. In 2014, Dr Rehm has been a visiting researcher at the Chinese Academy of Sciences, where he contributed to work on cancer stem cells and cell reprogramming. Dr Rehm has published >40 peer reviewed papers in the scholarly literature and has successfully supervised >20 MSc students, PhD students and postdoctoral researchers. His publication record includes a range of highly cited papers that describe innovative research methodology which significantly extended the molecular understanding of cell death signalling in cancer and which provided unique insight into mechanisms of cancer treatment resistance. In translational studies, his team integrates biological pathway knowledge and quantitative proteomic data to develop innovative and superior biomarker discovery strategies. Dr Rehm has been an invited speaker at more than 40 scientific conferences and workshops and contributes regularly to training initiatives in newly emerging applications in biophotonics, systems biology and systems medicine. His research is supported by the RCSI Research Committee, Science Foundation Ireland, the Health Research Board Ireland, the Higher Education Authority Program for Research in Third-Level Institutions Cycle 4, the Irish Research Council, the EU framework programme 7, and the EU Horizon 2020 programme.

Thiosquaramides: A new class of pH switchable anion transporter Nathalie Busschaert,3 Robert B. P. Elmes,1, 2 Dawid D. Czech,3 Xin Wu,3 Isabelle L. Kirby,3 Evan M. Peck,4 Kevin D. Hendzel,4 Scott K. Shaw,4 Bun Chan,1 Bradley D. Smith,4 Katrina A. Jolliffe1 and Philip A. Gale3

1School of Chemistry (F11), The University of Sydney, Australia. 2 Department of Chemistry, Maynooth University, Co. Kildare, Ireland. 3 School of Chemistry, The University of Southampton, Southampton, UK. 4 Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, USA. Fax: +353-1-7083815, Tel: +353-1-7084615; E-mail: [email protected]

Anions are critical to the maintenance of life, with almost every biochemical process involving the recognition, transport or transformation of anions at some point. Realisation of this pivotal role has led to growing interest in the design of artificial anion receptors for recognition, sensing and transport applications in biochemistry and biomedicine. Our approach has centred on the development of diketocyclobutene derivatives and particularly squaramides which have seen a revival of interest in recent years. This versatile functional group has been exploited in diverse areas of chemical research from bioconjugation to organocatalysis and with their strong hydrogen bonding ability, in combination with a large degree of structural rigidity they have emerged as an important binding motif in supramolecular chemistry. Most recently, we have focused on structurally simple systems that can mediate anion transport across lipid bilayers in response to an external stimulus. This lecture will summarise some of our most recent investigations in this area.

Figure 1. pH switchable anion transporters

Reference: Thiosquaramides: pH switchable anion transporters. Busschaert, N.; Elmes, R. B. P.; Czech, D. D.; Wu, X.; Kirby, I. L.; Peck, E. M.; Hendzel, K. D.; Shaw S. K.; Chan, B.; Smith, B. D.; Jolliffe, K. A.; Gale, P. A. Chem. Sci., 2014, 5, 3617.

Biography Name: Robert Elmes

Affiliation: Department of Chemistry, Maynooth University, Co. Kildare, Ireland Email: [email protected] Web: www.maynoothuniversity.ie/chemistry/

Rob graduated from the University of Dublin, Trinity College in 2007 having undertaken his final year project at the Institut des Biomolécules Max Mousseron, Université Montpellier I, France under the supervision of Prof. Thierry Durand. In 2007 he was awarded an IRCSET Embark Scholarship to undertake his PhD under the supervision of Prof. Thorri Gunnlaugsson at TCD where his research concerned the design, synthesis and evaluation of new metal complexes and nanomaterials as DNA probes and photoreagents. After a short postdoctoral tenure at the Trinity Biomedical Sciences Institute in Dublin, Rob moved to The University of Sydney under the guidance of Prof. Kate Jolliffe. Here, he was involved in the development of new platforms for the recognition, sensing and transport of biologically relevant anions. In late 2014, Rob returned to Ireland taking up a lecturing position at Maynooth University where he is currently a Lecturer in Organic Chemistry within the Department of Chemistry. Rob’s research interests lie in the fields of Supramolecular Chemistry and Chemical Biology where the group is trying to develop areas in both health- and nano- science. Rob’s current research concerns designing biomimetic materials as drug delivery vehicles, diagnostic tools, antitumor therapeutics and environmental sensors.

The Roles and Mechanisms of MicroRNAs in Chemically Induced Carcinogenesis

Yiguo Jiang

Abstract: MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that function primarily as oncogenes and tumor suppressors by mediating translational repression or mRNA degradation via binding target genes. In our study, malignant human bronchial epithelial cells transformed by benzo[a]pyrene were used to help characterize the possible mechanisms of miRNA function in chemically induced lung carcinogenesis. We found that miR-106a, miR-494 or miR-22 might function as oncogenes in cell transformation and that tumor suppressor RB1 is one of targets of miR-106a, and PTEN gene is a target of miR-494 and miR-22. Our study on miR-506 and miR-622 revealed that they act as anti-oncogenic miRNAs by regulating N-Ras and K-Ras respectively in transformed bronchial epithelial cells. Using rat models, we performed a systemic study on serum miRNA expression levels at different stages of tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl) -1- butanone (NNK)-induced lung carcinogenesis. We found that NNK exposure changes the expression of serum miRNAs, and serum miR-206 and miR-133b could potentially serve as a biomarker for lung carcinogenesis induced by NNK. In the study on gastric carcinogenesis, our results indicate that miR-21 contributes to gastric tumorigenesis induced by carcinogenic N-nitroso compound N-methyl-N-nitro-N'-nitrosoguanidine (MNNG). We comfirmed that FASLG plays an essential role as a mediator of the biological effects of miR-21 in gastric tumorigenesis. Furthermore, we found that the G/A polymorphism in miR-27a gene (rs11671784) results in significantly reduced expression of mature miR-27a and an increased level of its target HOXA10, reduces gastric cancer risk, and plays a role in gastric tumorigenesis. Our study also revealed that let-7a is significant in suppressing gastric cancer growth in vivo and in vitro. The identification of oncogenic and anti-oncogenic miRNAs could provide new insight into the molecular mechanisms and potential biomarkers of chemical carcinogenesis.

Biography:

Yiguo Jiang has completed his Ph.D in 2001 from Huazhong University of Science and Technology and postdoctoral studies from University of New Mexico. He is the director of Institute for Chemical Carcinogenesis and vice dean and professor of Public Health School, Guangzhou Medical University. He is also a PI of State Key Laboratory of Respiratory Disease, China. He has published more than 70 papers. His current research interest is in microRNA involved in chemical carcinogenesis.

GMU and Dong Fang Hotel

Guangzhou Medical University Add: 195, Dongfeng Xi Road, Guangzhou City, China Postal Code: 510182 Tel: (86)020-37103045 Website: http://www.gzhmu.edu.cn

Dong Fang Hotel (Guangzhou) 120 Liu Hua Road, Guangzhou 510016 P.R.C. Tel.: (8620) 86669900 Fax: (8620) 86662775 E-mail: [email protected] URL: www.hoteldongfang.com

2015 ISCP-China Biomedical Workshop