Innovative therapies, gene editing, and pre-clinical models in rare diseases
Tipologia: Ematologia
About 3.5%-5.9% of the worldwide population is currently affected by rare diseases that for 72% are caused by genetic defects and for the rest by infectious, allergies and environmental factors. Over 6000 different rare diseases are known so far, but due to the low prevalence of each of them, medical expertise is underdeveloped, knowledge is scarce, care offerings inadequate and research limited.
In our UOR a multidisciplinary team is focus on the study of rare diseases taking advantage of molecular, biochemical, physiological and pathological complementary expertises and cutting-edge- technologies linking clinical to basic sciences for the benefit of patients.
Starting from a patient center view, our research is dedicated on the generation of in vitro and in vivo models of rare diseases. The most recent gene editing techniques as well as deep molecular, biochemical and high-resolution imaging characterization will be employed, thanks to the availability of state-of-the-art aiming to identify new targets for the development of innovative and precision medicine based therapies.
- Tonelli F., Cotti S., Leoni L., Besio R., Gioia R., Marchese L., Giorgetti S., Villani S., Gistelinck C., Wagener R., Kobbe B., Fiedler I.A.K., Larionova D., Busse B., Eyre D., Rossi A., Witten P.E., Forlino A. Crtap and p3h1 knock out zebrafish support defective collagen chaperoning as the cause of their osteogenesis imperfecta phenotype. Matrix Biology, 2020;
- Paganini C., Gramegna Tota C., Monti L., Monti I., Maurizi A., Capulli M., Bourmaud M., Teti A., Cohen-Solal M., Villani S., Forlino A., Superti-Furga A., Rossi A. Improvement of the skeletal phenotype in a mouse model of diastrophic dysplasia after postnatal treatment with N-acetylcysteine. Biochemical Pharmacology, 2021;
- Leoni L., Tonelli F., Besio R., Gioia R., Moccia F., Rossi A., Forlino A. Knocking out TMEM38B in human foetal osteoblasts hFOB 1.19 by CRISPR/Cas9: A model for recessive OI type XIV. PLoS One, 2021;
- Nato G., Corti A., Parmigiani E., Jachetti E., Lecis D., Colombo M.P., Delia D., Buffo A., Magrassi L. Immune-tolerance to human iPS-derived neural progenitors xenografted into the immature cerebellum is overridden by species-specific differences in differentiation timing. Scientific Reports, 2021;
- Grisan F., Iannucci L.F., Surdo N.C., Gerbino A., Zanin S., Di Benedetto G., Pozzan T., Lefkimmiatis K. PKA compartmentalization links cAMP signaling and autophagy. Cell Death & Differentiation, 2021.
- Pre-clinical animal imaging facility: micro computed tomography (Skyscan μCT 1276, Bruker); dMRI (MRI RI 7T, Brucker); Integrating Gold Standard Bioluminescence and Fluorescence In Vivo System (Lumina III, PerkinElmer); Faxitrox-MX20 cabinet X-Ray system (Faxitron Bioptics); CosMx Spatial Molecular Imager (Nanostring);
- NMR (NMR Avance Neo 700MHz Bruker);
- Mass Spectrometry Facility (UHPLC-HRMS/MS- AB Sciex X500B; LC/MS Thermo Scientific LCQ Fleet; GC-MS/MS TSQ QUANTUM Thermo Scientific; GC/MS Thermo Scientific DSQ II);
- Histological platform (embedding station, microtome RM2265 and cryostat CM1850UV, Leica);
- Confocal and electron microscopy facility (DMI 6000; TCS SP8 DLS; SP5; TCS SP8 STED 3X, Leica; Transmission Electron Microscope JEOL JEM-1200EXIII equipped with TEM CCD camera Mega View III, Ultramicrotome Reichert Ultracut S, Instrumentation for preparing and manipulating biological samples);
- Live cell imaging: Olympus IX83 equipped with double CCD camera, optosin25, 6 Ultrafast filter wheel, and double light source (LED and Argon), all run by MetaFluor software. Microscope fully capable of Fluorescence Resonance Energy Transfer (FRET)-based live cell, real-time experiments;
- Cytofluorimetry and cell sorting: BD FACS Lyric (Becton Dickinson); ImageStreamX Mark II (Amnis/Luminex); Sorter BD FACS Aria III (Becton Dickinson).
- 2022-2026 HORIZON-MSCA-2021-DN-01- 101072766 - Cellular Homeostasis ANd AGing in Connective TissuE Disorders (Change);
- 2023-2024 IRCCS Fondazione San Matteo- Calcific aortic valve disease: a multidisciplinary approach to investigate the role of bacteria as trigger of a chronic inflammation in the pathogenesis of calcification;
- 2021-23 R21-NIH Grant - 1R21HD106607-01 Novel bone specific pharmacological treatment for osteogenesis imperfecta;
- 2020-23 Bando Ricerca Finalizzata, Ministero della salute- RF-2019-12369368. Mendelian Genetics 2.0: dissecting the clinical and genetic heterogeneity of ciliophaties as a model to unravel the complexity of “simple” recessive disorders”;
- 2023-2024 Telethon GMR22T1024. The mechanism behind trimeric intracellular cation channel B function in Osteogenesis Imperfecta skeleton;
- 2022-25 Human Frontiers Program Grant, (RGP0024/2022), “Unravelling the code of mitochondrial-nuclear communication”;
- 2021-2026 AIRC investigator grant ”Investigating the functional significance of nuclear EPAC1 condensates in cancer”.
- Sergey Leikin, Ph.D., Chief, Section on Physical Biochemistry, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD;
- Ken Kozloff, Ph.D., Associate Professor, Department of Orthopaedic Surgery, Co-Director, Exercise and Sport Science Initiative, University of Michigan;
- Paul Coucke, Prof. Dr. Ing., Department of Medical Genetics, MRB, Ghent University Hospital, Ghent, Belgium;
- Valérie Cormier-Daire, Prof. Dr., Paris Cité University, INSERM UMR1163, Imagine Institute, Service de Génétique clinique, Centre de référence pour les maladies osseuses constitutionnelles, AP-HP, Hôpital Necker-Enfants malades, Paris, France;
- Andrea Superti-Furga, Prof. Dr., Division of Genetic Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland;
- Brigitte M. Städler, PhD., Associate Professor, Interdisciplinary Nanoscience Center - INANO-MBG, iNANO-huset, Aarhus University, Denmark;
- Nikolaos Daskalakis, MD, PhD, Director, Neurogenomics and Translational Bioinformatics Laboratory,McLean Hospital, Assistant Professor, Harvard Medical School, Boston, USA.
GROUP LEADER: Prof.ssa FORLINO Antonella
GROUP MEMBERS:
Prof.ssa Roberta Besio (UNIPV), Prof. Ermanno Gherardi (UNIPV), Prof. Konstantinos Lefkimmiatis (UNIPV), Prof. Lorenzo Magrassi (IRCCS), Dr.ssa Chiara Paganini (UNIPV), Dr.ssa Francesca Tonelli (UNIPV).
Ultimo aggiornamento: 11/12/2025
