to the approaches of Systems Biology and Medicine M Giovanna Trivella National Research Council CNR Institute of Clinical Physiology Pisa amp MilanoItaly INFNCNR meeting CNAO Pavia 29 February 2016 ID: 934181
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IFC-CNR: from the complex scenarios of interdisciplinarity to the approaches of Systems Biology and MedicineM. Giovanna TrivellaNational Research Council (C.N.R.) Institute of Clinical Physiology, Pisa & Milano,Italy
INFN-CNR meetingCNAO Pavia 29 February 2016
Slide2INFN-CNR meetingCNAO Pavia 29 February 2016
Translational research from bench to bedside and viceversa
Slide3INFN-CNR meetingCNAO Pavia 29 February 2016Some examples from bibliographic references
M. Giovanna Trivella, Giuseppe Rainaldi:
SCIENTIFIC REPORT ESF Exploratory Workshop on Molecular Signaling in Cardiovascular and Oncological Diseases: Similar and Shared Pathways. EW07-013 – EMRC n.30, 2008
Patent:Inventors: Cinti Caterina, Settimio Grimaldi. Title “Erythrocyte-based delivery system, method of preparation and uses thereof” International Pub. Date 24 June 2010,
N. WO2010/070620C. Cinti et al Newly engineered magnetic erythrocytes for sustained and targeted delivery of anti-cancer
therapeutic compounds.
PLoS One. 2011 Feb 23;6(2):e17132.
Caterina Lande et al
Innovative erythrocyte-based carriers for gene delivery in porcine vascular smooth muscle cells: basis for local therapy to prevent restenosis.
Cardiovascular & hematological disorders drug targets 2012: 12:68-75
I Naldi et al
Novel epigenetic target therapy for prostate cancer: a preclinical study.
PLoS One. 2014 May 22;9(5):e98101.
Slide4INFN-CNR meetingCNAO Pavia 29 February 2016
Some examples from bibliographic references
Mariama El Baroudi et al.Immuno-mediated pan-cancer regulation networks are dominant fingerprints after cell lines treatment with demethylation. Cancer Informatics Journal 2016 (in press)
F Malusa et al.Time-course gene profiling and networks in demethylated retinoblastoma cell line.
Oncotarget 2015 Sep 15;6(27):23688-707 M El Baroudi Pathway landscapes and epigenetic regulation in breast cancer and melanoma cell lines.
Theor Biol Med Model 2014 May 7;11 Suppl 1:S8.
A Mora et al.
Ensemble inference by integrative
cancer networks.
Front Genet 2014 Mar 31;5:59.
G Pelosi et al.
Inflammation blood and tissue factors of
plaque growth in an experimental model
evidenced by a systems approach.
Front Genet DOI 10.3389/fgene.2014.00070
Capobianco E, Trivella MG (2014)
Networks: Elucidating Experimental Data
by Differential Protein-Protein Interactions.
J Comp Sys Bio 1(1): 101
Slide5INFN-CNR meetingCNAO Pavia 29 February 2016
Exploring some interactions
Analytical Chemistry & MedicineMarkers of Health/Diseases/Substances/Drugs
Breath, sweat, saliva ad dialysis fluid
F. Di Francesco et al.
Breath analysis: trends in techniques and clinical applications.
Microchemical Journal 79 (2005) 405– 410
Pietro Salvo et al.
Wearable Sensor for Measuring Sweat Rate.
IEEE SENSORS JOURNAL, VOL. 10, NO. 10, OCTOBER 2010
Silvia Ghimenti et (2011).
Measurement of Warfarin in the Oral Fluid of Patients Undergoing Anticoagulant Oral Therapy.
PLOS ONE, vol. 6; p. e28182-, ISSN: 1932-6203, doi: doi:10.1371/journal.pone.0028182
Michael Lee et al.
A novel biosensor based on hafnium oxide: Application for early stage detection of human interleukin-10.
Sens. Actuators B: Chem. (2012),
http://dx.doi.org/10.1016/j.snb.2012.04.090
Abdoullatif BARAKET et al.
A Flexible Label-Free Biosensor Sensitive and Selective to TNF-
α:
Application for Chronic Heart Failure.
Sensors & Transducers, Vol. 27, Special Issue, May 2014, pp. 15-21
Silvia Ghimenti et al.
Determination of sevoflurane and isopropyl alcohol in exhaled breathby thermal desorption gas chromatography–mass spectrometry for exposure assessment of hospital staff.
Journal of Pharmaceutical and Biomedical Analysis 106 (2015) 218–223
Slide6INFN-CNR meetingCNAO Pavia 29 February 2016
Proteomics
, PI: Silvia
Rocchiccioli
Identification
of
protein
biomarkers
by
hypothesis-free
or
targeted
analysis
Proteomics
profiling
for
differential
analysis
Quantitative mass
spectrometry
for
metabolites
,
lipids
and
proteins
Post-traslational
modification
proteomics
Oligonucleotide-based
Technologies, PI: Lorena TedeschiOligos as Biorecognition elements for Biosensors, In vitro diagnostics and Molecular imagingOligos for Gene/Function knock down
Oncogenomics, ITT-IFC, PI: Laura PolisenoStudy of microRNA- and ceRNA-based regulatory networks in melanomamicroRNAs and pseudogenes as new biomarkers, drugs and targets in melanomaDevelopment of innovative delivery strategies for metastatic melanoma
Technologies
Omics
(exome-seq, RNA-seq, mass spectrometry)FACSCapillary ElectrophoresisOligonucleotide Synthesis and modificationFluorescence microscopy
Model
systems
Zebrafish
Yeast
Mouse
Cell
culture
Yeast
Genetics and
Genomics
,
PI: Alvaro Galli and Tiziana CervelliHeterologous protein expressionGenome-wide screening to identify functional interactors of proteins involved in melanoma and breast cancerCharacterization of proteins involved in drug response and sensitivity Developing functional assays to characterize mutation in breast and melanoma tumor genes
Functional
Genomics and Geneticslab
Non-coding RNA, PI: Milena Rizzo and Letizia Pitto
Identification of new non-coding RNA based regulatory network in tumor biology and in cardiovascular disease
Development of new miRNA-based therapeutic strategies in prostate cancer and congenital heart disease (Holt Oram syndrome)
Discovery of circulating miRNA as predictive biomarkers of drug resistance in prostate cancer and diagnostic biomarker in pathological cardiac remodeling
Slide7Slide8METABOLOMICS IDENTIFICATION OF PROGNOSTIC AND DIAGNOSTIC BIOMARKERS OF
HEPATOCELLULAR CARCINOMA
META-LIVER
PI:
Dr. Amalia
Gastaldelli
co-PI:
Dr. Silvia Del
Ry
and
Dr.Giuseppina
Basta
National Research Council (C.N.R.)
Institute of Clinical Physiology, Pisa, Italy
Slide9INFN-CNR meetingCNAO Pavia 29 February 2016
METABOLIC FACTORS LEAD TO NASH/HCC
Slide10TASK 1p<0.0001
p<0.0001
p<0.05
0
50
100
150
200
250
HCC
Fatty liver
CT
AAA
umol
/L
4.2
4.7
5.2
5.7
6.2
Ln
(
AAAs
)
-1.5
-1
-.5
0
.5
1
1.5
2
2.5
3
3.5
HOMA
p<0.0001
R=0.61
4.2
4.7
5.2
5.7
6.2
Ln
(
AAAs
)
-.5
0
.5
1
1.5
2
2.5
3
3.5
4
adipoIR
p<0.0001
R=0.48
AROMATIC AMINOACIDS (
AAAs
) INCREASED WITH THE WORSENING OF LIVER DISEASE AND INSULIN RESISTANCE
Slide11INFN-CNR meetingCNAO Pavia 29 February 201611
Systems Medicine results
Tuulia Hyötyläinen et al.Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease
NATURE COMMUNICATIONS | 7:8994 | DOI: 10.1038/ncomms9994/ Published 3 Feb 2016
Slide12Example of protocol for Systems Medicine Subjects > 65 yrs with or without mild cognitive impairmentClinical characterization Cardiovascular and muscular
Holter ECG 24 hours WinPack (ECG, SO2, respiration, posture, physical activity,Tp)
Flow Mediated Dilation
Carotid stiffness Fatigue (sEMG)
Sleep and psychometric characterization Olfactometry tests
Metabolism
Subcutaneous Fat (*)
Protocol steps:
Time 0 after 6 months after 12 months
Personalized protocol with life style therapeutical indications (diet),
daily physical activity, recovery of physiologic sleep
(
* Time 0 and after 12 months)
INFN-CNR meeting
CNAO Pavia 29 February 2016
Slide13INFN-CNR meetingCNAO Pavia 29 February 2016
Systems Medicine Road Map
Big Data Complexity in the Medical Arena
Pan European Networks
Science & Technology 13, December 2014
Slide14INFN-CNR meetingCNAO Pavia 29 February 2016
Grazie per l’attenzione
IFC tra interdisciplinarietà e complessità di dati
dall'arena
clinica