Teh Boon Eng, PhD

Teh Boon Eng, PhD

Field Applications Specialist – Greater Asia

boon-eng.teh@fluidigm.com

 

“Dissecting cancer heterogeneity with mass cytometry”

Abstract

Biology is heterogenous. To understand the complexity of biology, a tool that allows for simultaneous measurement of the multiple different cell type and the depths of each individual cell function is required for a holistic understanding of the biological system of interest. Mass cytometry is a platform that is uniquely positioned to address this. Using antibodies tagged with stable metal isotopes of defined mass, we could routinely measure up to 40-plus different markers simultaneously at single cell resolution in a single tube. This efficient, high-information-per-tube approach is particularly valuable when working with precious clinical samples. The capability of this platform in understanding cancer biology and biomarker discovery will be discussed in this talk.

Biodata

Dr Teh is a Field Applications Specialist at Fluidigm supporting mass cytometry product franchise. He is equipped with 3 years plus worth of experience supporting mass cytometry instruments and reagents within the Greater Asia.

He obtained both his BSc (Hons) and PhD from National University of Singapore. His PhD project is on immunology and infectious disease where he focused on understanding the dynamics on how pathogens evade host immune surveillance and at the same time how host cell sense presence of pathogens and elicit an immune response against it. Shortly after obtaining his PhD he joined Vela Diagnostics to develop various diagnostic kits for detection of various pathogens prior to joining Fluidigm as Field Application Specialist.

Crispin Dass

Prof. Crispin R Dass,
School of Pharmacy and Biomedical Sciences,
Faculty of Health Sciences.,
Curtin University, Australia
Tel: 08 9266 1489
Email: Crispin.Dass@curtin.edu.au

 

CURRICULUM VITAE

Professor Dass majored in Medical Biotechnology, with a first class Honours from Charles Sturt University, NSW. He then obtained a doctorate in the field of Biomedical Sciences, in the area of cancer therapy, at the same University. Prof. Dass has 25 years of basic and applied research in cancer, with skills such as in vivo (small animal) and cell culture testing experience and significant drug formulation and delivery skills. His PhD project, on targeted gene therapy for cancer, in the mid-90s, was one of the earliest applications of gene transfer in Australia. He is well-versed in medium-throughput screening of potential lead compounds for cancer drug R&D, and he has worked on bigpharma projects (Amgen, Novartis, Glaxo-Wellcome, Johnson & Johnson) in oncology and drug testing. Prof. Dass also has 24 years of experience using a wide range of molecular techniques including real-time PCR, western blotting, immunohistochemistry and molecular therapy. Prof. Dass has been at a lab leadership role for the past 11 years, all in the area of cancer drug discovery, delivery and development.

 

ABSTRACT

Pigment epithelium-derived factor (PEDF) possesses evolutionary-diversified roles that include the regulation of angiogenesis, neural stem cell survival and differentiation, antioxidant function in the eye, pro-differentiation in the bone, and growth inhibition in a variety of cancers. PEDF is downregulated in breast cancer patients.  Of note, PEDF has a high affinity binding site for collagen I, the major protein found in bone, as well as glycosaminoglycans (GAGs) such as heparin and hyaluronan, which play important roles in bone formation. We have demonstrated that PEDF downregulates MT1-MMP expression in a variety of cancer cells including the ER breast cancer cell line MDA-MB231. Osteoclasts play a dominant role in breast cancer metastases to bone. The human ER+ breast cancer cell line MCF-7 secretes RANKL, which promotes osteoclastogenesis and subsequent bone mineral resorption. RANKL and RANK are expressed by mammary epithelial cells under the control of sex hormones, and RANK and RANKL control the preferential metastasis of breast cancer cells to the bone. We demonstrated that PEDF downregulates osteoclast differentiation, survival and activity via upregulation of osteoprotegerin (OPG), a decoy for RANKL. More recently, we have shown that PEDF is able to induce bone regeneration. This now allows us to use this versatile protein in not only controlling primary tumour spreading to the bones, but also repairing the damage done at the bone lesion sites. Results of studies with two tumours, osteosarcoma and breast cancer, will be discussed.

 

John E Connolly

Professor Dr John Connolly, PhD
Chief Scientific Officer
Tessa Therapeutics Pte Ltd
Singapore
E-mail: johneconnolly@tessatherapeutics.com

Title:  Virus Specific T cells as platform for Solid Tumor Immunotherapy

 

CURRICULUM VITAE   

Professor Connolly is the CSO of Tessa Therapeutics, a Senior Principal Investigator and Director for Translational Immunology at the Institute of Molecular and Cellular Biology (IMCB).  As a human immunologist, his research interests focus on target discovery for immune modulation.  An Adjunct Associate Professor of Immunology at Baylor University, he served on the Board of Governors for the Institute of Biomedical Sciences.

Professor Connolly received his Ph.D. in Immunology from Dartmouth Medical School and studied human dendritic cell biology under Dr. Michael Fanger.  During this time, he was involved in the development of immunotherapeutic preclinical models and clinical trials for Glioblastoma multiforme (GBM).  He moved to the Baylor Institute for Immunology Research, a fully translational research institute dedicated to rationally designed vaccines against cancer and infectious disease.  Professor Connolly served as the Director of Research Initiatives for the Baylor Research Institute, leading a large integrated translational research resource and multi-institutional programs.  During his tenure at Baylor, Professor Connolly was a central core facility director of the NIAID Centers for Translational Research on Human Immunology and Biodefense, an NIH funded consortium of basic, translational research and clinical trials focused on vaccine design.  Professor Connolly is the past President of the Board of Directors of The American Cancer Society in N. Texas

 

Title: Virus Specific T cells as platform for Solid Tumor Immunotherapy

Abstract:

The ability to simultaneously monitor changes in multiple immune parameters holds great discriminatory and instructive power for the purpose of biomarker validation and mechanistic target discovery. In the case of Virus Specific T cell therapy for solid tumors, an examination of the systemic, cellular and local immune environment during the course of treatment has yielded a series of predictive biomarkers correlating with immunogenicity, response to therapy and overall survival on trial.  An analysis of antigen specific T-cells have identified anti-viral responses with positive prognostic value. Differences in the immunosuppressive state of the patient’s activated regulatory T-cells (Tregs) and the expansion or contraction of the myeloid-derived suppressor cell (MDSC) compartment, point to a mechanism of action for the therapy.

Publications of direct relevance to the study

Qamra A, Xing M, Padmanabahn N, Kwok JJ, Zhang S, Chang X, Leong YS, Lee Lim AP, Tang Q, Ooi W, Suling Lin J, Nandi T, Yao X, Ong X, Lee M, Tay ST, Keng AT, Gondo Santoso E, Ng CC, Ng A, Jusakul A, Smoot D, Ashktorab H, Rha SY, Yeoh KG, Peng Yong W, Chow PK, Chan WH, Ong HS, Soo KS, Kim KM, Wong WK, Rozen SG, Teh BT, Kappei D, Lee J, Connolly J, Tan P. Epigenomic promoter alterations amplify gene isoform and immunogenic diversity in gastric adenocarcinoma. Cancer Discovery, Mar 2017: Epub ahead of print [PMID: 28320776]

Ang WX, Li Z, Chi Z, Du SH, Chen C, Tay JC, Toh HC, Connolly JE, Xu XH, Wang S. Intraperitoneal immunotherapy with T cells stably and transiently expressing anti-EpCAM CAR in xenograft models of peritoneal carcinomatosis, Ocnotarget, Feb  2017; 8(8): 13545-13559 [PMID: 28088790]

Thornhill SI, Mak A, Lee B, Lee HY, Poidinger M, Connolly JE, Fairhurst AM. Monocyte Siglec-14 expression is upregulated in patients with systemic lupus erythematosus and correlates with lupus disease activity, Rheumatology, Jan 2017: Epub ahead of print [PMID: 28137763]

Zhong FL, Mamai O, Sborgi L, Boussofara L, Hopkins R, Robinson K, Szeverenyi I, Takeichi T, Balaji R, Lau A. Tye H, Roy K, Bonnard C, Ahl PJ, Jones LA, Baker P, Lacina L, Otsuka A, Fournie PR, Malecaze F, Lane EB, Akiyama M, Kabashima K, Connolly JE, Masters SL, Soler VJ, Omar SS, McGrath JA, Nedelcu R, Gribaa M, Denguezli M, Saad A, Hiller S, Reversade B. Germline NLRP1 Mutations cause skin inflammatory and cancer susceptibility syndromes via inflammasome activation, Cell, Sept 2016: Vol 167 (1), Pg 187-202  [PMID: 27662089]

Sung C, Wei Y, Watanabe S, Lee HS, Khoo YM, Fan L, Rathore AP, Chan KW, Choy MM, Kamaraj US, Sessions OM, Aw  P, de Sessions PF, Lee B, Connolly JE, Hibberd ML, Vijaykrishna D, Wijaya L, Ooi EE, Low JG, Vasudevan SG. Extended evaluation of virological, immunological and pharmacokinetic endpoints of CELADEN: A randomized, Placebo-controlled trial of Celgosivir in dengue fever patients, PLoS Negl Trop Dis, Aug 2016 10(8) [PMID:27509020]

 

Marco Falasca

Prof Marco Falasca
Head Metabolic Signalling Group
School of Pharmacy and Biomedical Sciences
Faculty of Health Sciences
Curtin University

E-mail : marco.falasca@curtin.edu.au

CURRICULUM VITAE

Marco Falasca had his formal training in pharmacology and Pharmaceutical Chemistry with research experience in cell biology (signal transduction) and cancer pharmacology (enzymology).  He received the Pharmaceutical Chemistry degree (summa cum laude) from the University of Camerino, Italy and the Ph.D.eq degree from the Istituto Mario Negri Sud, in 1985 and 1994, respectively. From 1995 to 1997, M. Falasca was a Postdoctoral of the Department of Pharmacology at New York University. From 1998 to 2000 he was group leader at Consorzio Mario Negri Sud, Italy. From 2001 to 2007 M. Falasca was appointed as a Principal Research Fellow at University College London, Department of Medicine. From 2007 to 2014 he was appointed as a Professor at the Blizard Institute, Queen Mary University of London. In 2014, he was recruited by Curtin University, Perth, Australia, to establish a Metabolic Signalling group and held a Chair in Metabolism. The focus of his research in the past 30 years involved the investigation of signalling pathways regulating intracellular physiological and pathological processes. His work is mostly focused on intracellular signals regulated by specific lipids that act as “second messengers” inside a cell to control a plethora of cellular functions, including cell growth, proliferation and metabolism. Attention is specifically focused on lipids known as “phosphoinositides” that can themselves act as or be converted into messengers, ultimately regulating several cellular functions.

RESEARCH INTEREST

  1. i) Identification of novel therapeutic strategies for pancreatic cancer
  2. ii) Importance of deregulation of lipid metabolism in cancer biology

iii) The biology and function of exosomes in cancer

  1. iv) Exosomes as biomarkers for the early detection of pancreatic cancer

RECENT KEY PUBLICATIONS

Falasca M, Casari I, Maffucci T. Cancer chemoprevention with nuts. J Natl Cancer Inst. 2014, 106(9).

 

Franco I, Gulluni F, Campa CC, Costa C, Margaria JP, Ciraolo E, Martini M, Monteyne D, De Luca E, Germena G, Posor Y, Maffucci T, Marengo S, Haucke V, Falasca M, Perez-Morga D, Boletta A, Merlo GR, Hirsch E. PI3K class II α controls spatially restricted endosomal PtdIns3P and Rab11 activation to promote primary cilium function. Dev Cell. 2014 Mar 31;28(6):647-58.

 

Cheung K, Ma L, Wang G, Coe D, Ferro R, Falasca M, Buckley CD, Mauro C, Marelli-Berg FM. CD31 signals confer immune privilege to the vascular endothelium. Proc Natl Acad Sci U S A. 2015 Oct 27;112(43):E5815-24.

 

Braccini L, Ciraolo E, Campa CC, Perino A, Longo DL, Tibolla G, Pregnolato M, Cao Y, Tassone B, Damilano F, Laffargue M, Calautti E, Falasca M, Norata GD, Backer JM, Hirsch E. PI3K-C2γ is a Rab5 effector selectively controlling endosomal Akt2 activation downstream of insulin signalling. Nat Commun. 2015 Jun 23;6:7400.

 

Falasca M, Kim M, Casari I. Pancreatic cancer: Current research and future directions. Biochim Biophys Acta. 2016 Apr;1865(2):123-32.

 

Chikh A, Ferro R, Abbott JJ, Piñeiro R, Buus R, Iezzi M, Ricci F, Bergamaschi D, Ostano P, Chiorino G, Lattanzio R, Broggini M, Piantelli M, Maffucci T, Falasca M. Class II phosphoinositide 3-kinase C2β regulates a novel signaling pathway involved in breast cancer progression.  Oncotarget. 2016 Apr 5;7(14):18325-45.

 

Marat AL, Wallroth A, Lo WT, Müller R, Norata GD, Falasca M, Schultz C, Haucke V. mTORC1 activity repression by late endosomal phosphatidylinositol 3,4-bisphosphate. Science. 2017 Jun 2;356(6341):968-972.

 

Simpson PV, Casari I, Paternoster S, Skelton BW, Falasca M*, Massi M*. Defining the Anti-Cancer Activity of Tricarbonyl Rhenium Complexes: Induction of G2/M Cell Cycle Arrest and Blockade of Aurora-A Kinase Phosphorylation. Chemistry. 2017 May 11;23(27):6518-6521.

 

Title: EXOSOMES IN PANCREATIC CANCER DIAGNOSIS AND THERAPY

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) accounts for approximately 90% of pancreatic malignancies, with a post-diagnosis 5-year survival rate of less than 5%. Due to lack of clinical symptoms, sufferers tend to be diagnosed late in the disease progression. In order to deliver effective therapies, specific biomarkers are needed for early detection. Lipids have been proposed as potential biomarkers for many forms of cancer. Furthermore, exosomes play a multifaceted role in cancer progression and are providing new opportunities for biomarkers discovery. We focus on the discovery of novel exosome-associated lipid biomarkers for PDAC and compare with prostate and ovarian cancer, to identify a specific PDAC signature. Exosomes were successfully isolated from PDAC and normal pancreatic cell lines conditioned media, and together with their corresponding cells, they were subjected to lipidomic analysis using HPLC-ESI-MS/MS to detect over 700 lipid species from 25 lipid classes and subclasses. MS-based proteomic analysis was performed, to verify the lipidomic findings. PDAC-derived exosomes were found to have a distinct lipid composition compared to their corresponding cells and exosomes derived from healthy cells. Exosome were greatly enriched in cholesterol, sphingomyelin and saturated fatty acids, compared to the derived cells. Unusual lipid species were also detected, along with important proteins involved in lipid biology. PDAC-derived exosomes not only carry precious lipidomic information which can be exploited for the discovery of novel prognostic and diagnostic biomarkers, but also provide us with crucial information about the tumour biology and progression of the disease. Indeed, exosomes released by cancer cells carry specific molecules that act as messages and their abundance reflects the metastatic potential of the cancer. Therefore, the molecular composition in these cancer exosomes could help in the progression of the cancer and represents a cancer-specific signature.

MBDB2018 Committee members

MDBD 2019 : Antibody Engineering Organising Team, 25-26 September 2018

Chair:
Assoc. Prof. Dr. Choong Yee Siew

Co-Chair :
Dr. Tye Gee Jun

 

Advisors:
Professor Rahmah Noordin, PhD, FASc,
Director, INFORMM, USM

Associate Profesor. Dr. Lim Theam Soon
HICoE Programme Leader, INFORMM, USM

 

Secretary
Khairul Mohd Fadzli Mustaffa
Mohamad Fadhzli Abdul Wahab
Sponsorship
Lim Theam Soon
Treasurer
Noral Wiah Hj. Abd. Karim
Mohd Nasir Yusuf
Publicity
Leow Chiuan Yee
Scientific
Leow Chiuan Herng
S.Sasidharan
Hospitality & Technical
Venugopal Balakrishnan