Title: Sox2, more than a transcription factor Speaker: Dr. Pengyan Xia

Dr. Pengyan Xia

Sox2, more than a transcription factor

Date: Thursday 30thApril 2015

Dear Colleagues,

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

Dr Xia’s research is focussed on
studying development and differentiation of the haematopoietic system, in
particular in self-renewal of haematopoietic stem cells (HSCs) and anti-microbe
activity of white blood cells that derived from HSCs. Specifically, his
research is focussed on signalling platforms that regulate the
self-renewal of HSCs (Xia et al, J Exp Med 2014) as well as extracellular
DNA triggered innate immunity in neutrophils (Xia et al, Nat Immunol 2015).

You are all very welcome to attend, please register at:csm@rcsi.ie


Markus Rehm

Centre for Systems Medicine, Department of Physiology and Medical Physics

Royal College of Surgeons in Ireland

Funded by the International Strategic Cooperation
Award (ISCA) Grant Number SFI/13/ISCA/2845 China

MEL-PLEX Worshop Wednesday 6th May 2015

Innovative Approaches in Translational Melanoma Research

MEL-PLEX is a Marie Skłodoswska-Curie
Innovative Training Network funded by Horizon 2020 aiming to train a new
generation of researchers that can navigate confidently between clinical,
academic and private sector environments. As part of its training programme,
MEL-PLEX will hold a training course which will consist of workshop to provide
an overview of the current status of malignant melanoma management and the
field of translational cancer systems biology and systems medicine, followed by
a Transferable Skills course to introduce the new PhD students to basic topics
in scientific research.

The main topics addressed

  • Melanoma
    pathology and treatment
  • Melanoma
    proliferation and migration
  • Kinase
    cascades in melanoma
  • Cell
    death modalities in melanoma
  • Biomarker
    identification and validation
  • Targeted
    drugs and drug development
  • Innovative
    experimental models
  • Applied
    Systems Biology
  • Systems
    Medicine strategies

The workshop entitled “Innovative
Approaches in Translational Melanoma Research” is an open event. Deadline for
registration is April 24th 2015.

For more information and free
registration please contact: melplexETN@rcsi.ie

Venue: Cheyne Lecture Theatre, RCSI, 9am
Wednesday 6th May 2015

Seminar: “Systems pharmacology and pharmacokinetic/pharmacodynamic modelling Oncology”

The Centre for
Systems Medicine is delighted to announce
distinguished  speakers to its 2015 seminar series:

Prof. Donald Mager
, Associate Professor of Pharmaceutical Sciences at the University at Buffalo, State University of New York (UB) 
Bio: -http://pharmsci.buffalo.edu/CEPKPD/faculty/MAGER.HTML


Prof.Robert Straubinger, Professor of Pharmaceutical
at University at Buffalo School of Pharmacy.

Bio: -http://pharmsci.buffalo.edu/CEPKPD/faculty/STRB.HTML

Houston Lecture Theatre, RCSI, 4.30 Pm Tuesday 10th March 2015


Congratulations to Dr. Lorna Flanaghan on winning a poster prize at the The Irish Association for Cancer Research 2015 meeting


L.Flanagan, S.Curry, M. Meyer, J. Fay, O. Bacon, E.W. Kay, D.A. McNamara, and J.H.M. Prehn

‘’We examined the role of executioner caspases in tissue regeneration following chemotherapy.Exploiting and antagonising this paracrine role of executioner caspases may be an interesting, novel approach for the treatment of tumours characterised by
resistance and relapse. Our data highlight that inhibition of Caspase-3, or
antagonising downstream effectors of Caspase-3 paracrine signalling, may
represent a novel approach to halt, or at least impede, tumour cell repopulation
following chemotherapy’




A systems biological analysis of apoptosome formation and apoptosis execution supports allosteric procaspase-9 activation.

The protease caspase-9 is activated on the apoptosome, a multi-protein signal transduction platform that assembles in response to mitochondria-dependent apoptosis initiation. Despite extensive molecular research, the assembly of the holo-apoptosome and the process of caspase-9 activation remain incompletely understood. Here we therefore integrated quantitative data on the molecular interactions and proteolytic processes during apoptosome formation and apoptosis execution, and conducted mathematical simulations to investigate the resulting biochemical signalling, quantitatively and kinetically.

Interestingly, when implementing the homo-dimerisation of procaspase-9 as a prerequisite for activation, the calculated kinetics of apoptosis execution and the efficacy of caspase-3 activation failed to replicate experimental data. In contrast, assuming a scenario in which procaspase-9 is activated allosterically upon binding to the apoptosome backbone, the mathematical simulations quantitatively and kinetically reproduced all experimental data. These data included a XIAP threshold concentration at which apoptosis execution is suppressed in HeLa cervical cancer cells, half-times of procaspase-9 processing, as well as the molecular timer function of the apoptosome.

Our study therefore provides novel mechanistic insight into apoptosome-dependent apoptosis execution and suggests that caspase-9 is activated allosterically by binding to the apoptosome backbone. Our findings challenge the currently prevailing dogma that all initiator procaspases require homo-dimerisation for activation.

J Biol Chem. 2014 Aug 8. pii: jbc.M114.590034. [Epub ahead of print]

A systems biological analysis of apoptosome formation and apoptosis execution supports allosteric procaspase-9 activation.

Würstle ML(1), Rehm M(2).

Author information:

(1)Royal College of Surgeons in Ireland, Ireland.

(2)Royal College of Surgeons in Ireland, Ireland mrehm@rcsi.ie

“Abeta oligomers and brain inflammation link synapse failure to neuronal insulin resistance and depression in Alzheimer’s disease”

The Centre for Systems Medicine is delighted to announce another speaker to its 2015 seminar series: 

  Prof. Sergio T. Ferreira.

Professor of Biophysics,Biochemistry, and Neuroscience,

Institute of Biophysics Carlos Chagas Filho & Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio
de Janeiro

 Venue: Albert Lecture Theatre, RCSI, 9am Friday 27th February 2015

Lecture entitled: ‘”Abetaoligomers and brain inflammation link synapse failure to neuronal insulinresistance and depression in Alzheimer’s disease”

Prof. Ferreira has  over  15 years extensive experience in investigating molecular and cellular mechanisms leading to synapse failure and memory loss in Alzheimer’s disease.His main research focus has been on understanding intracellular signaling pathways disrupted or altered when neurons are exposed to Ab oligomers, both in vitro and in vivo.
With particular interest in mechanisms leading to mood alterations in AD and in
shared mechanisms of pathogenesis between AD and diabetes. http://www2.bioqmed.ufrj.br/ldn/sergio.html

All very welcome to attend,

Prof. Jochen Prehn

World Cancer Day Today, 4th February 2015

Cancer Research – Past, Present and Future. Leading Irish and International scientists discuss how cancer research and treatment has evolved in recent years, and what the future holds.


Systems Medicine symposium, BREAST-PREDICT,Irish Cancer
Society Collaborative Cancer Research Centre marking World Cancer Day, 4th February 2015.





‘Genetics of Diabetes’ Prof. Graeme Bell, University of Chicago

The Centre for
Systems Medicine is delighted to announce another speaker to its 2015 seminar

Prof. Graeme Bell

University of Chicago

Houston Lecture Theatre, RCSI, 4.30pm Thursday 22nd January 2015

‘Genetics of Diabetes’

Dr. Bell’s research
focuses on the genetics of diabetes mellitus and the biology of the
insulin-secreting pancreatic beta-cell.

 He and his colleagues
are using various genetic approaches to map and identify the genes that affect
development of type 2 diabetes mellitus as well as diabetic complications. They
carry out studies in both humans and mouse models to determine the mechanisms
by which the diabetes genes they identify affect blood glucose levels. Their
studies of pancreatic beta-cells are focused on understanding the
transcriptional regulatory networks that determine normal cell function.



  All very welcome to
attend, Prof. Jochen Prehn




CSM Seminar: Single-cell insights into population-level heterogeneity with examples of MAPK, HIF response and ubiquitination systems

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

Dr. Maciej Dobrzynski

Systems Biology Ireland, University College Dublin, Belfield, Dublin 4


Title: Single-cell
insights into population-level heterogeneity with examples of MAPK, HIF
response and ubiquitination systems

Venue: Nightingale Theatre, Thursday 15th
Jan 2015 4pm.

All welcome to attend, 

Prof. Jochen Prehn



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: