Dott.ssa Laura Follia
- MEDICINA MOLECOLARE
- Dottorato: 30° ciclo
- Matricola: 727610
Contatti
- 3,90116E+11
- laura.follia@unito.it
- Via Pessinetto 12, 10149 Torino, Italy
- https://dott-mm.campusnet.unito.it/do/studenti.pl/Show?727610
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Supervisore
Francesco NovelliTesi di dottorato
Pancreatic Cancer (PDA) is a highly lethal and treatment resistant malignancy. It is predicted to become the second leading cause of death in the next decades. At the time of diagnosis, only 20% of patients present in situ and potentially resectable tumors. The overall 5-year survival rate for these patients is <5% The poor prognosis is due to the failure of early diagnosis and to the presence of extensive clonal heterogeneity in primary tumors. For these reasons, there is an urgent need to characterize the PDA subtypes.
Many recent studies used transcriptomic data to sub-classify PDA cancers, and such studies revealed that different patient outcomes and drug sensitivity can be due to different PDA subtypes.
One main feature of PDA that leads to its aggressive behavior is its altered glucose metabolism. Indeed, it is well known that the KRAS aberrant signaling pathway in PDA increases the expression of many glycolytic enzymes fueling PDA and it highlights that glycolysis plays an important role in its development.
We integrate different omics data to identify clinically relevant metabolic subtypes in pancreatic cancer. We propose a novel approach that leads to the identification of two main metabolic subtypes, defined as glycolytic and non-glycolytic. Patients with the glycolytic subtype develop tumors earlier, they have poor prognosis, higher disease recurrence and a different immune infiltrate.
By focusing our attention on this group, we find that it is characterized by the recurrent genomic gain of chr12p13 region resulting in an over expression of GAPDH, TPI1, ENO2 genes.
To validate our results, we performed a proteomic analysis on PDA patients sera. Our proteomic analysis reveals that serum levels of TPI1 are higher in patients with a poor outcome.
To fully understand and successfully manipulate the PDA glycolytic pathway, we also use the Petri Nets formalism to investigate temporal behavior of biochemical reactions. For this purpose, many kinetic characteristics would be needed but many of them are still unavailable. To cope with this problem, we model pancreatic cancer metabolism with a novel method that allows to tackle situations where the information about kinetic parameters is partially missing.
Omics data are a big source of information. From the integration of their analyses it is possible to classify cancers with clinically relevant differences. However, these data represents static information that does not reflect the dynamicity of metabolism. Thus, for a complete investigation of PDA metabolic features omics data must be integrated with a dynamic metabolic modeling. In this thesis we study metabolism of PDA tumors through omics data and the system biology approach.
Attività di ricerca
I'm interested in the area of omics data integration, next generation sequencing data analysis and in systems biology.
The aim of my work is the study of the mutational profile of Pancreatic Ductal Adenocarcinoma (PDAC). In particular, I'm studying the mutational profile of PDAC in order to find new mutations involved in the pancreatic carcinogenesis and also to study the clonal relationship among primary and metastatic cancers.
Piaggeschi G, Licheri N, Romano G, Pernice S, Follia L and Ferrero G. MethylFASTQ: a novel tool to simulate bisulfite sequencing data. Accepted for PDP Conference 2019.
Follia L , Ferrero G, Mandili G, Beccuti M, Giordano D, Spadi R, Satolli M A , Evangelista A, Katayama H, Hong W, Momin A A, Capello M, Hanash S M, Novelli F and Cordero F. Integrative analysis of novel metabolic subtypes in pancreatic cancer fosters new prognostic biomarkers. Frontiers in Oncology. Under Review.
L. Follia, F. Tordini, S. Pernice, G. Romano, G. Piaggeschi, G. Ferrero. ParallNormal: An Efficient Variant Calling Pipeline for Unmatched Sequencing Data. 26th Euromicro International Conference on Parallel, Distributed and Network-based Processing (PDP), 21-23 March, Cambridge (UK) 2018.
N. Totis, L. Follia, F. Cordero, C. Riganti, F. Novelli, G. Balbo and M. Beccuti. Overcoming the lack of kinetic information in biochemical reactions networks. ACM SIGMETRICS Performance Evaluation Review, Volume 44 Issue 4, March 2017
Pages 91-102.
N. Totis, M. Beccuti, F. Cordero, L. Follia, C. Riganti, F. Novelli, and G. Balbo. Dealing with indetermination in biochemical networks. Accepted for INFQ, New Frontiers in Quantitative Methods in Informatics, October 2016, Taormina.
Follia L., Ferrero G., Mandili G., Beccuti M., Katayama H., Wang H., Momin A. A., Capello M., Hanash S. M., Novelli F. and Cordero F. Integrative Analysis of novel metabolic subtypes in pancreatic cancer fosters new prognostic biomarkers. DDAY 2018, Turin, Italy, September 13, 2018.
Follia L., Ferrero G., Mandili G., Beccuti M., Katayama H., Wang H., Momin A. A., Capello M., Hanash S. M., Novelli F. and Cordero F. An integrative transcriptomic analysis of glycolytic genes reveals distinct metabolic subtypes in pancreatic cancer. BITS annual meeting 2018, Turin, Italy, June 27-29, 2018. Best poster award.
Mandili G., Follia L., Ferrero G., Katayama H., Wang H., Momin A. A., Capello M., Cordero F., Hanash S. M. and Novelli F. Chemotherapy effects on immune-complexes in pancreatic ductal adenocarcinoma patients serum. International Proteomics&Metabolomics conference. High-throughput MS-based proteomics and metabolomics: from cells to clinic, Novara, Italy, June 25, 2018.
S. Bulfamante, G. Mandili, M. Principe, D. Giordano, E. Mazza, C. Curcio, L. Follia, G. Ferrero, A. Evangelista, M. Satolli, P. Cappello, F. Novelli; Antibody and T cell response profiling in pancreatic cancer patients before and after chemotherapy identify tumor associated antigens suitable for immunotherapy. AACR 2018. 14-18 April 2018, Chicago Illinois.
G. Mandili, M. Principe, E. Mazza, S. Bulfamante, L. Follia, G. Ferrero, A. Evangelista, D. Giordano, P. Cappello, F. Novelli. Antibody and T cell response profiling of pancreatic cancer patients before and after chemotherapy reveals increased recognition of antigens suitable for immunotherapy. SITC (Society for Immunotherapy of Cancer) 2017, 32nd annual meeting, National Harbor, MD, November 10-12, 2017. Published in Journal for ImmunoTherapy of Cancer 2017, 5(Suppl 2):87 DOI 10.1186/s40425-017-0288-4
Follia L., Mandili G., Ferrero G., Beccuti M., Cordero F., Katayama H., Wang H., Momin A. A. , Capello M. , Hanash S. M. and Novelli F. . Proteomic data analysis of pancreatic cancer patient sera revealed how chemotherapy shapes the immunogenicity of developing tumors. ISMB/ECCB 2017. Prague, Czech Republic 21-25 July 2017.
S. Bulfamante, G. Mandili, M. Principe, E. Mazza, L. Follia, G. Ferrero, A. Evangelista, P. Cappello, F. Novelli. Identification of chemotherapy-induced antigens suitable for immunotherapy in pancreatic cancer patients . EACR-AACR-SIC 2017- Special Conference. Florence, Italy, 24-27 June 2017.
Follia L , Ferrero G , Totis N, Riganti C, Novelli F, Balbo G, Beccuti M and Cordero F. Inspecting Energy-Releasing Pathways by a combination of genomics data and mechanistic approach. 12-15 November, EMBO Conference: From Functional Genomics to Systems Biology 2016, Heidelberg (Germany).
Follia L, Ferrero G, Totis N, Riganti C, Novelli F, Balbo G, Beccuti M and Cordero F. Inspecting Energy Realising Pathways by a combination of genomics data and mechanistic approach. September 3-7, ECCB 2016, The Hague (Netherlands).
Novelli F, Mandili G, Mazza E, Bulfamante S, Giordano D, Follia L, Cappello P. Chemotherapy induces a coordinate autoantibody and T-cell response against tumor-associated antigens in pancreatic cancer patients. April 16-20, AACR Annual Meeting 2016, New Orleans, LA (USA).
Beccuti M, Totis N, Follia L,Calogero R,Cordero F, Balbo G. Modeling biological systems considering the uncertainty associated with model parameters. BITS annual meeting 2016. Salerno, Italy, 15-17 June.
Totis N, Fornari C, Follia L, Riganti C, Beccuti M, Novelli F, Balbo G and Cordero F. Computational modelling of pancreatic cancer cells metabolism. BITS annual meeting 2015. Milan, Italy, 3-5 May 2015.
Michela Capello, Sammy Ferri-Borgogno, Moitza Principe, Michelle Samuel Chattaragada, Chiara Riganti, Weidong Zhou, Laura Follia, Lance A. Liotta, Emanuel F. Petricoin III, Paola Cappello, Francesco Novelli. Alpha-enolase knockdown reprograms metabolism and points out targetable pathways to counteract PDA growth. May 18-21, 2014 AACR Special Conference in Pancreatic Cancer: Innovations in Research and Treatment, Hyatt Regency New Orleans, New Orleans, LA (USA).
D-Day 2018. September 2018, Turin (Italy).
BITS annual meeting 2018, June 27-29, Turin (Italy).
Gut Microbiota for Health World Summit, March 2018, Rome (Italy).
D-Day 2017. September 2017, Turin (Italy).
"ISMB-ECCB 2017", 20-26 Luglio 2017, Prague Czech Republic.
D-Day 2016. September 2016, Turin (Italy).
SummerCourse: "Intrinsic and Innate Immunity to Pathogens" , 23-35 June 2016, Novarello Congress Center, Granozzo con Monticello, Novara (Italy).
ECCB 2016, 3-7 September 2016. The Hague (Netherlands).
First Piedmont Bioinformatics Day, 22 September 2016. MBC, Turin (Italy)
Il Trasferimento di conoscenze in Ateneo: dalla ricerca alla valorizzazione, 3 Febbraio 2015, Torino, Italy.
Frontiers in Rigenerative Medicine. February 19-20, 2015. MBC, Turin, Italy.
RNAseq Workshop, An introductory course to RNA-seq. March 2015, MBC, Turin, Italy.
D-Day 2015. September 2015, Turin, Italy
Valorizzare le competenze dei dottorati di ricerca ed accompagnarli nel mondo del lavoro. October 2015 Turin, Italy.
"Next generation sequencing in diagnostica", Dott. Davide Gentilini (Istututo auxologico di Milano) 26 Gennaio 2016 (MBC, Torino)
4 Marzo 2016 "Cancer metabolism: unexspected observations and possible ex- planations" Alex Vazquez (Bateson Instutute Cancer Reasearch UK - Glasgow), MBC Torino.
Workshop: "ENABLING TECHNOLOGIES IN 3D CANCER ORGANOIDS" 8-9 Marzo 2016, MBC Turin, Italy.
"Analisi non convenzionale dell'esoma: Runs Of Homozygosity e Varianti Strut- turali", Relatore: Dr. Tommaso Pippucci (U.O. Genetica Medica, Policlinico Sant'Orsola Malpighi, AOU Bologna. MBC Torino 14 Giugno 2016.
"Neutral evolution in cancer: distinguishing functional from nonfunctional intra- tumour heterogeneity", Relatore: Dr. Andrea Sottoriva (The Institute of Cancer Research, London UK). IRCC Candiolo 19 Settembre 2016.