Centro Interdipartimentale di Biotecnologie Molecolari "Guido Tarone"
Riccardo Taulli - PI
Associate Professor, University of Torino
- Francesca Bersani, PhD - Assistant Professor
- Francesca Picca, PhD - Post-doctoral Fellow
- Virginia Botta, Lucia Giordanengo, Hafiz Muhammad Waqas Munir, Jiahao Tao - PhD Students
- Michele Sornatale - Research Fellow
- Margherita Lambertini - Master Student
Research activity
Since the early stages of my scientific career, I have contributed to define the role of the HGF/MET axis in tumorigenesis. The expertise gained in gene silencing/expression allowed me to generate vector cassettes for the conditional expression of long and short RNAs, including microRNAs, lncRNAs and, more recently, circRNAs. By the employment of these genetic tools, I defined the biological significance of several microRNAs involved in c-Met regulation as well as in the control of epigenetic programs disrupted in cancer. During my training in the US, I acquired novel skills in RNA biology, in generating Genetically Engineered Mouse Models (GEMMs) and in deconstructing complex cancer phenotypes using genomic analyses and innovative pre-clinical platforms. In 2014, I moved back to Turin and thanks to an AIRC-StartUp Grant, I established my independent research group. The research carried out in my lab is mainly focused on coding and non-coding RNA regulatory circuits involved in tumor development and evolution, with the long-term aim to develop novel therapeutic strategies for cancer treatment. As the Head of the Laboratory of Molecular Biochemistry and Translational Oncology at the Department of Oncology, I have carried out deep ncRNA profiling approaches to identify novel actionable targets in cancer treatment (Oncogene 2015, Cell Cycle 2015; Cancer Res 2016). Concomitantly, we have generated a versatile GEMM for conditional and tissue-specific expression of HGF. This model revealed a critical role of the tumor microenvironment, exemplified by HGF, in the maintenance of stem cell quiescence as well as in the selection and expansion of rare MET-amplified subclones as a mechanism of acquired resistance (Elife, 2016). Moreover, we have recently demonstrated in primary co-cultures that specific epigenetic drug treatments exert a dual benefit by inhibiting cancer cell proliferation and playing an instructive role on the autologous immune system (Oncoimmunology 2018). Our current effort is focused on understanding the key molecular determinants of lung cancer adaptation and evolution under molecular targeted therapy pressure (JECCR 2023; Crit Rev Oncol Hematol 2024; IJMS 2024).
We are developing a platform of tumor-derived organoids from advanced NSCLC to define the complex genetic and transcriptional interplay underlying lung cancer adaptation, persistence and evolution under molecular therapy pressure. By exploiting genomic profiling, microfluidic technologies, pharmacogenetic screening and functional validation analyses we aimed at identifying novel predictive biomarkers of tumor response and key molecular determinants involved in lung cancer plasticity and evolution. This approach will shed light on novel targetable therapeutic avenues for intercept and abrogate therapy evasion.
AIRC Start-Up Grant-15405 and AIRC-IG-25978 to R.T.; Italian Ministry of University and Research (RILO to R.T.); University of Turin, Progetti Ateneo, Compagnia di San Paolo Excellent Young PI (to R.T.). Grant for Internationalization to F.B.; National Foundation for Cancer Research Grant to F.B., PRIN 2022 to F.B., Fondazione CRT to (F.B.).
Picca F, Giannotta C, Tao J, Giordanengo L, Munir HMW, Botta V, Merlini A, Mogavero A, Garbo E, Poletto S, Bironzo P, Doronzo G, Novello S, Taulli R, Bersani F. From Cancer to Immune Organoids: Innovative Preclinical Models to Dissect the Crosstalk between Cancer Cells and the Tumor Microenvironment. Int J Mol Sci. 2024; 25(19):10823.
Bersani F, Picca F, Morena D, Righi L, Napoli F, Russo M, Oddo D, Rospo G, Negrino C, Castella B, Volante M, Listì A, Zambelli V, Benso F, Tabbò F, Bironzo P, Monteleone E, Poli V, Pietrantonio F, Di Nicolantonio F, Bardelli A, Ponzetto C, Novello S, Scagliotti GV, Taulli R. Exploring circular MET RNA as a potential biomarker in tumors exhibiting high MET activity. J Exp Clin Cancer Res. 2023;42:120.
Toyokawa G, Bersani F, Bironzo P, Picca F, Tabbò F, Haratake N, Takenaka T, Seto T, Yoshizumi T, Novello S, Scagliotti GV, Taulli R. Tumor plasticity and therapeutic resistance in oncogene-addicted non-small cell lung cancer: from preclinical observations to clinical implications. Crit Rev Oncol Hematol. 2023 Apr;184:103966.
Riganti C, Lingua ML, Salaroglio IC, Falcomatà C, Righi L, Morena D, Picca F, Oddo D, Kopecka J, Pradotto M, Libener R, Orecchia S, Bironzo P, Comunanza V, Bussolino F, Novello S, Scagliotti GV, Di Nicolantonio F, Taulli R. Bromodomain inhibition exerts its therapeutic potential in malignant pleural mesothelioma by promoting immunogenic cell death and changing the tumor immune-environment. Oncoimmunology. 2017DOI:10.10 80/2162402X.2017.1398874.
Bersani F, Lingua MF, Morena D, Foglizzo V, Miretti S, Lanzetti L, Carrà G, Morotti A, Ala U, Provero P, Chiarle R, Singer S, Ladanyi M, Tuschl T, Ponzetto C, Taulli R. Deep Sequencing Reveals a Novel miR-22 Regulatory Network with Therapeutic Potential in Rhabdomyosarcoma. Cancer Res. 2016;76:6095-6106.
Morena D, Maestro N, Bersani F, Forni PE, Lingua MF, Foglizzo V, Šćepanović P, Miretti S, Morotti A, Shern JF, Khan J, Ala U, Provero P, Sala V, Crepaldi T, Gasparini P, Casanova M, Ferrari A, Sozzi G, Chiarle R, Ponzetto C, Taulli R. Hepatocyte Growth Factor-mediated satellite cells niche perturbation promotes development of distinct sarcoma subtypes. Elife. 2016 doi: 10.7554/ eLife.12116.
Guarnerio J, Riccardi L, Taulli R, Maeda T, Wang G, Hobbs RM, Song MS, Sportoletti P, Bernardi R, Bronson RT, Castillo-Martin M, Cordon-Cardo C, Lunardi A, Pandolf PP. A genetic platform to model sarcomagenesis from primary adult mesenchymal stem cells. Cancer Discov. 2015;5:396-409.
Lunardi A, Varmeh S, Chen M, Taulli R, Guarnerio J, Ala U, Seitzer N, Ishikawa T, Carver BS, Hobbs RM, Quarantotti V, Ng C, Berger AH, Nardella C, Poliseno L, Montironi R, Castillo-Martin M, Cordon-Cardo C, Signoretti S, Pandolf PP. Suppression of CHK1 by ETS Family Members Promotes DNA Damage Response Bypass and Tumorigenesis. Cancer Discov. 2015;5:550-63.
Taulli R, Foglizzo V, Morena D, Coda D, Ala U, Bersani F, Maestro N, Ponzetto C. Failure to downregulate the BAF53a subunit of the SWI/SNF chromatin remodeling complex contributes to the diferentiation block in rhabdomyosarcoma. Oncogene 33:2354-62, 2014
Kats LM, Reschke M, Taulli R, Pozdnyakova O, Burgess K, Bhargava P, Straley K, Karnik R, Meissner A, Small D, Su SM, Yen K, Zhang J, Pandolf PP. Proto-oncogenic role of mutant IDH2 in leukemia initiation and maintenance. Cell Stem Cell. 2014;14:329-41
Taulli R, Bersani F, Foglizzo V, Linari A, Vigna E, Ladanyi M, Tuschl T, Ponzetto C. The muscle-specifc microRNA miR-206 blocks human rhabdomyosarcoma growth in xeno-transplanted mice by promoting myogenic diferentiation. J Clin Invest. 119:2366-78, 2009.
