CSM contributes to European Roadmap for Systems Medicine

The CASyM roadmap is published

After a two year cross-disciplinary consultation process, the Coordinating Action Systems Medicine (CASyM) has published its European implementation strategy (roadmap) for Systems Medicine.  The vision of this roadmap is to develop Systems Medicine into a practical framework that assists clinical decision making and the design of personalised prevention and treatment plans. Central to this is a systems approach that addresses clinical questions and provides solutions to the most pressing clinical challenges such as the results of an ageing population, increased needs for social care and a growing burden of curing and caring for patients with cancer. The roadmap which was authored and reviewed by multiple European academic and industry partners, including Prof. Jochen Prehn, Director of the Centre for Systems Medicine (RCSI), is available for download below:

https://www.casym.eu/index.php?index=90

Decisions, decisions: Regulation of apoptotic and necroptotic cell death in skin cancer.

Friday 5th December 2014, at 2.00 pm

Decisions, decisions:  Regulation of apoptotic and necroptotic
cell death
in skin cancer

Dr Martin Leverkus

Section for Molecular Dermatology, Department of Dermatology and
Allergology, Medical Faculty Mannheim, University of Heidelberg, Germany.

Dear Colleagues,

The Centre for Systems Medicine is pleased to announce another speaker of our seminar series.

Dr Leverkus’s research
is focussed on studying regulation of cell death in the skin under
physiological and pathophysiological conditions, in particular in skin cancer
cells. Specifically, his research is focussed on signalling platforms that
regulate decision processes in cell death research (Feoktistova et al, Mol CELL
2011; Panayotova-Dimitrova et al, CELL Reports 2013) as well as the impact of
small molecule inhibitors of cell death pathways (Geserick et al, Cell Death
& Disease 2014).

The talk will be held in the Houston
Lecture Theatre at 2.00pm 5th
December 2014.

You are all very welcome to attend.

Regards, Markus Rehm

“Searching for factors that can protect pancreatic beta-cells in diabetes using biased and unbiased approaches”

Albert Lecture Theatre, 4pm, Tuesday 28th of October 2014.

James D. Johnson, Ph.D.

Oxford University Visiting Professor of Integrated Physiology, OCDEM/WTCHG,Visiting Fellow of Harris-Manchester College Associate Professor | Medicine |
Cellular and Physiological Sciences, Surgery Diabetes Research Group, Cardiovascular Research Group The University of British Columbia| Canada

Jim Johnson is Associate Professor in the
Department of Cellular and Physiological Sciences and Department of Surgery at
the University of British Columbia. He is a founding member of the Diabetes
Research Group at the Life Sciences Institute at UBC. He is Editor-in-Chief of
the journal Islets, and on the Editorial Board of Diabetes and Endocrinology.
An expert in the fundamental biology of diabetes and related conditions, he is
the author of over 93 peer-reviewed articles since 2000. His work has been
published in some of the most prestigious and highly cited journals including Cell
Metabolism, Diabetes, Diabetologia, Endocrinology, PNAS, Nature Medicine
.

 His current research focuses on multiple
themes, including: type 1 diabetes, type 2 diabetes, obesity, heart disease,
neuroscience, pancreatic cancer, and longevity. He teaches human physiology to
large and small classes and directly mentors ~12 students and 5 post-doctoral
fellows in his laboratory. The work of his team involves a multidisciplinary
approach. His work has been funded by the JDRF, the Canadian Institutes of
Health Research, the Canadian Diabetes Association, the Stem Cell Network, the
Cancer Research Society, the Canada Foundation for Innovation, and other agencies.

We are delighted to welcome Prof. Johnson to RCSI and the Centre for Systems
Medicine and all very welcome to attend,

Prof.  Jochen Prehn

Exploiting addiction to apoptosis inhibitors in cancer

 Exploiting addiction to apoptosis inhibitors in cancer

Speaker: Dr Daniel Longley, Centre for Cancer Research and Cell Biology, Queen’s University Belfast
Monday 6th October 2014, at 4.00 pm

Dear Colleagues,

The Centre for Systems Medicine is pleased to announce another speaker of our seminar series, Dr Daniel Longley.

Dr Longley’s research is focussed on overcoming drug resistance by activating cell death (apoptosis) in cancer cells. Specifically, his research is centred on the
pre-clinical and clinical development of small molecule inhibitors of
anti-apoptotic proteins, including novel drug delivery strategies, and the
identification of predictive biomarkers to enable the targeted use of novel
anti-cancer therapeutics in molecularly-defined patient populations.

http://www.qub.ac.uk/researchcentres/CentreforCancerResearchCellBiology/Research/Staff/DrDanLongley/

The talk will be held in the Cheyne Lecture Theatre at 4.00pm 6th October 2014.

You are all very welcome to attend.

Regards,

Markus Rehm

Centre for Systems Medicine

Seminar: Pharmacogenomics of breast, colorectal, and pancreatic carcinomas

The RCSI Centre for Systems Medicine will host a seminar by Dr Pavel Souček (NIPH, Prague) on the molecular mechanisms of responses to major anticancer drugs by

Dr Pavel Souček

Head, Toxicogenomics Department & Group for Biotransformations, Centre of Occupational Medicine, National Institute of Public Health (NIPH), Prague, Czech Republic

Pharmacogenomics of breast, colorectal, and pancreatic carcinomas

Abstract: Response to anticancer therapy on the molecular level is limited by the inter-individual variability in drug metabolizing enzymes (e.g. cytochromes P450) and transporters as ATP-binding cassette (ABC) transporters or solute carrier (SLC) proteins. We followed associations of clinical features, including therapy outcome, with gene expression of more than 100 genes from pathways active in metabolism and transport of major anticancer drugs (anthracyclines, antimetabolites, taxanes) in sets of tumor and non-neoplastic tissues from breast, colorectal and pancreatic carcinoma patients.

We have found potential biomarkers of patient´s prognosis, e.g. ABCC11 in colorectal (Hlavata et al. Mutagenesis 2012) or ABCA12, ABCA13, ABCC1, ABCC8, and ABCD2 in breast carcinoma (Hlavac et al. Pharmacogenomics 2013). The observed, overexpression of multidrug-resistance connected exporters (ABC transporters) and downregulation of drug importers (SLCs) in pancreatic adenocarcinomas may contribute to the generally low treatment response of this cancer and suggests new drug targets (Mohelnikova-Duchonova et al. Pancreas 2013 and Cancer Chem Pharmacol. 2013).

Marked differences in expression profiles suggest that the followed carcinomas may differ in mechanisms of drug resistance. We are currently performing validation and mechanistic studies to verify the importance of the revealed biomarkers for cancer outcome.

All are welcome to the Albert LectureTheatre, RCSI 123 St Stephen’s Green on Tuesday August 26th at 4pm.

This seminar is supported by HRB funding to Dr David Hughes in the CSM

 

Low selenium levels are associated with colorectal cancer development

Low selenium levels are associated with colorectal cancer development

New evidence that the micronutrient selenium is involved in colorectal cancer (bowel cancer) has been discovered by Dr David Hughes from the Centre for Systems Medicine with colleagues in Emory University in Atlanta, Georgia, USA, the University of
Newcastle in England, the International Agency for Research on Cancer in Lyon,
France, and collaborators in the European Prospective Investigation of Cancer
and Nutrition Cohort (EPIC) study. The research is currently published online
(July 9th) in the International Journal of Cancer*

 The HRB funded research, led by Dr Hughes, indicates that selenium levels are suboptimal in many Western Europeans and suggest that higher serum selenium levels are associated with a decreased risk of colorectal cancer (CRC), which is more evident in women.

Many populations in Europe have intakes of selenium that are relatively low, especially compared with North America. The association of selenium status with CRC development is controversial due to conflicting results from both observational
studies and intervention trials.

The present study describes the results of the largest prospective analysis of the association of serum selenium status biomarkers [total serum Se levels and Selenoprotein P (SePP) protein concentrations] with risk of CRC in European populations. These are robust markers of Se status. The study was conducted within the EPIC cohort across ten European countries. This cohort provides a well-characterized, large set of participants in terms of diet and cancer risk.

The study shows that in many Western Europeans selenium levels are insufficient for adequate function of key proteins (such as SePP) that use selenium in important cellular processes. Higher selenium concentrations were inversely associated with CRC risk in women only while higher SePP concentrations were inversely associated with CRC risk in men and women combined. The results suggest that selenium intake/status is an important factor in affecting CRC risk in a population of marginally low
selenium status, such as in Europe.

The contrasting results of this study and those from the NPC and SELECT selenium intervention trials may be due to differences in baseline selenium levels of study participants. This likely helps to explain the controversy over outcomes from these selenium intervention trials in North America that has led to the prevalent perception among the scientific / medical community that increased selenium intake does not have any association with risk of CRC development. Our results suggest that in populations where selenium status is sub-optimal (e.g. Western Europe) increasing selenium intake may reduce CRC risk, especially for women. We believe our study provides a strong rationale for undertaking a selenium supplementation trial, including use of selenium status biomarkers, for CRC prevention in a population with sub-optimal Se availability.

*Manuscript reference:

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.<a href=”http://www.ncbi.nlm.nih.gov/pubmed/25042282
target=”_blank”> Selenium Status is Associated with Colorectal
Cancer risk in the European Prospective Investigation of Cancer and Nutrition
Cohort.</a> Int J Cancer. 2014 Jul 9. [Epub ahead of print] PMID:
25042282

APO-DECIDE Project

Link

At the threshold of personalised cancer treatment

Published by newsroom editor on Friday, 16/05/2014

New tumour profiling methods developed by EU-funded researchers aim to help doctors adjust treatments for colorectal cancer to the specific needs of an individual patient. The methods are currently at the trial stage and could be in use in clinics within three years.

Worldwide, colorectal cancer is responsible for around 694 000 deaths each year, according to the World Health Organization. Decision making on treatment in the clinic currently depends largely on factors such as how much the tumour has grown and the age of a patient. As each patient is unique, the success of such treatments is largely unpredictable.

To replace the ‘one size fits all’ approach, the APO-DECIDE project, led by Professor Jochen Prehn at the Royal College of Surgeons in Ireland, is developing new clinical decision-making tools to help doctors categorise patients on the basis of their individual biological and genetic characteristics.

Read More:http://ec.europa.eu/programmes/horizon2020/en/news/threshold-personalised-cancer-treatment

Common Gut Bacterium Associated with Colorectal Cancer

HRB-funded research in the Centre for Systems Medicine could lead to a new biomarker for colorectal cancer.

New evidence that a common gut bacterium is involved in colorectal cancer has been published by researchers in the Centre for Systems Medicine, RCSI (first author is Dr Lorna Flanagan and study PI is Dr David Hughes). The manuscript* is currently available online in the European Journal of Clinical Microbiology & Infectious Diseases.

The HRB funded research found a significantly increased presence of a common microbe Fusobacterium nucleatum (Fn) in tissue and stool samples of patients with colorectal cancers and colorectal adenomas. Additionally Fn infection levels were related with adenoma progression from early to advanced stages and the transition from an adenoma to cancer, highlighting the potential of Fn detection as a possible indicator of colorectal cancers. The research further found that cancer patients with low bacterial levels had significantly longer survival times than patients with moderate and high levels of the bacterium.

The research suggests that screening for Fn levels may be used as a new colorectal cancer detection method or to further inform existing screening strategies. Efforts to combat Fn infection could be considered for colorectal cancer patients with high levels of the bacterium to improve the survival prospects for these patients. Fn levels may be used to classify adenomas that may have a higher risk of disease progression to colorectal cancers with implications for increasing follow-up and at the possible use of anti-microbial treatments. Potentially, any impact of Fn infection on adenoma development and progression to more serious stages will be considerable, because 95% of all colorectal cancers arise from adenomas, but only a small number of them become cancerous. Currently, there are no reliable predictive markers of whether an adenoma will advance to cancer.

Seminar by Prof. Borner on use of viruses and funghi in apoptosis research

The Centre for Systems Medicine is pleased to announce another speaker to our seminar series,

Prof Dr Christoph Borner

Professor in Medical Cell Research, Institute of Molecular Medicine,
Albert Ludwigs University Freiburg, Germany

Use of viruses and funghi to uncover novel apoptosis signaling pathways

The primary interest of his laboratory is the elucidation of the function of multidomain anti- and pro-apoptotic Bcl-2 family members (Bcl-2, Bcl-xL, Mcl-1, Bax and Bak), the characterization of components of caspase-independent and RNA-virus (SFV)-induced apoptosis signaling, and the mathematical modelling of apoptotic and mitogenic FasL signaling pathways in primary hepatocytes.

Find more details on his homepage.

Recent publications:

  • A Novel Mitochondrial MAVS/Caspase-8 Platform Links RNA Virus-Induced Innate Antiviral Signaling to Bax/Bak-Independent Apoptosis. El Maadidi S, Faletti L, Berg B, Wenzl C, Wieland K, Chen ZJ, Maurer U, Borner C. J Immunol. 2014 Jan 3.
  • Apoptosis induced by the fungal pathogen gliotoxin requires a triple phosphorylation of Bim by JNK. Geissler A, Haun F, Frank DO, Wieland K, Simon MM, Idzko M, Davis RJ, Maurer U, Borner C. Cell Death Differ. 2013 Oct;20(10):1317-29. doi: 10.1038/cdd.2013.78. Epub 2013 Jul 5.
  • TNFα-induced lysosomal membrane permeability is downstream of MOMP and triggered by caspase-mediated NDUFS1 cleavage and ROS formation. Huai J, Vögtle FN, Jöckel L, Li Y, Kiefer T, Ricci JE, Borner C. J Cell Sci. 2013 Sep 1;126(Pt 17):4015-25. doi: 10.1242/jcs.129999. Epub 2013 Jun 20.
  • Non-canonical function of Bax in stress-induced nuclear protein redistribution. Lindenboim L, Ferrando-May E, Borner C, Stein R. Cell Mol Life Sci. 2013 Aug;70(16):3013-27.

The talk is open to everyone and will be held in Houston Lecture Theater, RCSI on 28th of January 2014 at 1:30 pm.

Seminar by Lou Philipson: New Insights into Insulin Secretion

The Centre for Systems Medicine is pleased to announce another speaker to our seminar series,

Prof. Lou Philipson,
Professor of Medicine, Director, Kovler Diabetes Center, The University of Chicago

New Insights into Insulin Secretion

Louis Philipson, MD, PhD, is an endocrinologist and a leading world authority on diabetes mellitus. His clinical interests include type 1 diabetes, complicated type 2 diabetes, monogenic diabetes and hypoglycemia.

Recognized for unmatched expertise in the treatment of diabetes that is difficult to manage, Dr. Philipson’s multisciplinary team frequently accepts referrals and provides consultations. Under his leadership, Kovler Diabetes Center has been recognized as a one of only seven National Institutes of Health (NIH) Diabetes Research and Training Centers in the U.S.

For more than 25 years, Dr. Philipson has tirelessly explored the biophysical, molecular and genetic aspects of insulin secretion, and the genetics of diabetes. He and his colleagues discovered rare insulin gene mutations that produce beta cell ER stress and, in turn, cause neonatal diabetes.

In addition, Dr. Philipson and his colleagues are among the nation’s leading experts on monogenic diabetes, following more than 100 patients diagnosed with neonatal diabetes and many others with maturity onset diabetes of the young (MODY) type diabetes. He also serves as co-director of the Human Islet Transplantation project at the University of Chicago.

Dr. Philipson has served as principal investigator on numerous research projects. His work is widely published in biomedical journals, including the Proceedings of the National Academy of Sciences, Science, Nature, Diabetes, American Journal of Physiology and the Journal of Biological Chemistry.

http://www.uchospitals.edu/physicians/louis-philipson.html

The talk is open to everyone and will be held in Houston Lecture Theater, RCSI on the 16th of January 201 at 4:30 pm.