Translational and Molecular Medicine – DIMET

The training project of DIMET focuses on Translational Medicine based on Molecular Medicine and Medical Biotechnologies. The course is interdisciplinary and internationalized through contacts with foreign research groups and research experiences abroad. Many DIMET doctoral students conduct part of their research and training activities in foreign laboratories. The training program is innovative and based on advanced didactics, with great attention to the developments of new biomedical technologies. Research activities within the DIMET doctoral program can start from both medical issues requiring the development of new biological systems and basic studies that can have a significant impact on medicine. The close relationship with the world of work is achieved through contacts in the healthcare sector, the bioindustry, and with international and national institutions of excellence.

The DIMET doctoral program is structured into 3 general research areas and 4 specialized areas of scientific research.

General research areas:

1) Cellular and molecular mechanisms. Understanding molecular and cellular mechanisms is of fundamental importance for studying specific diseases and for the development of new technologies that allow efficient diagnosis and effective therapy.

Dissection of cellular and molecular process networks leading to dysfunction of different organelles, cell types, and organs including:

• Mitochondria: bioenergetic profile and biogenesis (Prof. Valeria Sonia Tiranti)
• Role of the mitochondrial dysfunction as biomarker of frailty (Prof. Cristina Bianchi)
• Nuclear organization during cellular differentiation and diseases (Prof. Chiara Lanzuolo)
• Physiological and pathological aging (Prof. Chiara Lanzuolo)
• Haematopoietic cells (Prof. Luca Mologni; Prof. Emanuele Azzoni)
• Genetics of pediatric acute lymphoblastic leukemia (Prof. Giovanni Cazzaniga)
• Haemato-vascular development (Prof. Emanuele Azzoni)
• Vascular associated cells (Prof. Silvia Brunelli)
• Hemoglobin switching (Prof. Antonella Ellena Ronchi)
• Iron metabolism (Prof. Donatella Barisani)
• Transcriptional regulation in neural development and neurodevelopmental disorders, based on human hiPS-derived “brain” organoids and mouse cells (Prof. Silvia Nicolis)
• Neurons, synapses, glia (Prof. Silvia Barabino; Prof. Andrea Becchetti; Prof. Silvia Nicolis, Prof. Ilaria Rivolta)
• Skeletal muscle (Prof. Silvia Brunelli; Prof. Chiara Lanzuolo; Prof. Ilaria Rivolta)
• Cardiac muscle (Prof. Antonio Zaza; Prof. Ilaria Rivolta)
• Immunogenetics and pathogenesis of Autoimmune Liver Diseases (Prof. Pietro Invernizzi; Prof. Alessio Gerussi)
• Kidney-Molecular mechanisms of renal diseases (cancer and diabetic nephropathy)  (Prof. Cristina Bianchi)
• Manipulation of transposons and suicide genes (Prof. Andrea Biondi; Prof. Giuseppe Gaipa)
• Effect on lipidomic and metabolomic profiling, fatty acids and oxysterols of mitochondrial and peroxisomal dysfunction (Prof. Valerio Leoni)
• Role of the immune system-microbiome interaction in inflammatory bowel disease (IBDs) (Prof. Federica Facciotti)
• Enlightening of molecular mechanisms in the pathogenesis, progression and therapeutic responses of disease by MS-Proteomics (Prof. Fulvio Magni; Prof. Andrew Smith)
• Mechanism of bone disease in Lysosomal Storage Disorders (Prof. Marta Serafini)

2) Clinical and regenerative medicine. Clinical medicine refers to the development and implementation of advanced therapeutic approaches that may involve expertise in gene or cell therapy, tissue engineering, pharmacology and pharmacogenomics, and the development of new molecular therapies. In this area of ​​scientific investigations, researchers with clinical and basic research training converge and collaborate.

• State of the art in stem cell technology (Prof. Andrea Biondi; Prof. Marta Serafini; Prof. Silvia Brunelli; Prof. Silvia Nicolis; Prof. Cristina Bianchi; Prof. Chiara Lanzuolo; Prof. Pietro Genovese; Prof. Emanuele Azzoni; Prof. Ilaria Rivolta)
• Gene therapies (Prof. Andrea Biondi; Prof. Marta Serafini; Prof. Pietro Genovese)
• Chimeric antigen receptor in targeted therapy of leukemia (Prof. Andrea Biondi; Prof. Marta Serafini; Prof. Giuseppe Gaipa; Prof. Pietro Genovese)
• New experimental approaches for novel molecular target therapy (Prof. Carlo Gambacorti-Passerini; Prof. Marialuisa Lavitrano; Prof. Luca Mologni; Prof. Pietro Genovese)
• Preclinical modeling of cell-therapy in cancer (Prof. Andrea Biondi; Prof. Giovanna D’Amico; Prof. Marta Serafini; Prof. Pietro Genovese)
• Development of innovative preclinical models of immunotherapy in neuro-oncology, evaluating the impact of safety and transfer to the clinic. Tailor-made combinatorial strategies (i.e. radiotherapy or sonodynamic therapy) for immunotherapy in glioblastoma (Prof. Serena Pellegatta)
• Development of clinical-grade cellular therapies (Prof. Giuseppe Gaipa)
• Mesenchymal stromal cells for promoting repair in traumatic brain injury (Prof. Giuseppe Citerio; Prof. Giuseppe Gaipa)
• Metabolomics and Lipidomics in Clinical Pathology and Clinical Biochemistry. The use of mass spectrometry in the research of biomarkers (Prof. Valerio Leoni).
• Biomaterials for tissue regeneration and in vitro 3D cell cultures. 3D Bioprinting of implantable scaffolds (Prof. Laura Russo)

3) Technological platforms, nanomedicine and diagnosis. The development of new technological platforms, nanomedicine, new techniques for diagnosis, patient stratification or administration of therapeutic molecules are of fundamental importance for modern biomedicine. In this research area the projects are focused on: Identification of biochemical, molecular and proteomic markers related to the onset and progression of diseases, with particular reference to tumors and rare diseases and study of the biomedical applications of nanoparticles and their characterization for diagnostic purposes or therapeutic.

• Proteomics, Spatial multi-omics mass spectrometry imaging (Prof. Fulvio Magni; Prof. Andrew Smith; Prof. Fabio Pagni)
• Lipidomics, metabolomic and fluxomics (Prof. Giuseppe Paglia)
• Lipidomics and metabolomics in aging and degenerative diseases (Prof. Valerio Leoni)
• Mass spectrometry in Clinical Pathology and Diagnostic (Prof. Valerio Leoni)
• Advanced analytical mass spectrometry based approaches for diagnosis/prognosis/targeted therapy in human diseases (Prof. Fulvio Magni; Prof. Giuseppe Paglia;  Prof. Andrew Smith)
• Nanoparticles-cell/tissue interaction for imaging and drug delivery (Prof. Ilaria Rivolta; Prof. Giovanni Cazzaniga; Prof. Francesco Mantegazza)
• Design, synthesis and characterization of nanoparticles for therapy and diagnosis of human diseases (Prof. Francesca Re; Prof. Francesco Mantegazza; Prof. Claudia Corbo, Prof. Miriam Colombo)
• Use of nanoparticles for gene therapy and RNA delivery (Prof. Miriam Colombo; Prof. Francesca Re)
• Design of nanoparticles and implantable biomaterials for the therapy of brain disorders (Prof. Francesca Re)
• Investigation of the nanoparticles’ biomolecular corona for diagnosis and therapy of human diseases (Prof. Claudia Corbo)
• Development of nanosizedradiopharmaceuticals for PET (Prof. Francesca Re)
• Use of mass spectrometry in Diagnostics. Lipidomics and Metabolomics in Health and Disease (Prof. Valerio Leoni)
• Structural mass spectrometry (Prof. Carlo Santambrogio)
• Use of Cell Sorter platform for hematological, immunological and oncological studies (Prof. Cristina Bianchi)
• Advanced in vitro cellular models of biological barriers for nanomedicine research (Prof. Francesca Re)
• Nano-omics approaches for biomarkers discovery in human diseases (Prof. Claudia Corbo)
• Biomaterials for tissue regeneration and in vitro 3D cell cultures. 3D Bioprinting of implantable scaffolds (Prof. Laura Russo)
• Approaches for the clinical transition to Digital Pathology  (Prof. Fabio Pagni)
• Computational Pathology and Spatial Omics in Autoimmune Liver Disease (Prof. Pietro Invernizzi; Prof. Alessio Gerussi)

Specialized research areas:

1) Oncology and hematology disorders. Tumor pathologies are destined to become the first cause of death in the near future and this has led to an increase in scientific research conducted on all fronts of oncology, from the development of experimental models to advanced biological therapies, up to the development of diagnostic imaging and prevention. DIMET's research programs in this area are related to neoplastic transformation and growth, diagnosis and therapies in solid and hematological tumors.

• Molecular mechanisms of renal cancer invasion and progression - In vitro cellular models (Prof. Cristina Bianchi)
• Somatic lesions in cancer, cellular transformation, diagnosis and therapy (Prof. Rocco Piazza; Prof. Luca Mologni)
• Transcriptional control of erythropoietic cell differentiation and hemoglobin switching (Prof. Antonella Ellena Ronchi)
• Unraveling new metabolic vulnerabilities in acute leukemias (Prof. Angela Savino)
• Mouse modeling of pediatric myeloid malignancies (Prof. Emanuele Azzoni; Prof. Marta Serafini)
• Elucidation of acute leukemias mechanisms in the bone marrow niche (Prof. Marta Serafini)
• Design and synthesis of cell-mimicking nanoparticles for cancer therapy (Prof. Claudia Corbo)
• Development of drug delivery system for cancer therapy and diagnosis (Prof. Miriam Colombo; Prof. Francesca Re)
• In vitro tumor models in static and fluidic conditions for animal-free personalized drug testing (Prof. Laura Russo)
• Manipulation of the intestinal microbiome to enhance anti-tumorigenic immune cells’ functions in Colorectal cancer (Dr. Federica Facciotti)
• Molecular biology of epithelial ovarian cancer (Prof. Robert Fruscio)
• ctDNA for diagnosis and monitoring of advanced epithelial ovarian cancer (Prof. Robert Fruscio)
• Prevention of gynecological cancers in patients with pathogenic mutations (Prof. Robert Fruscio)

2) Neurodegenerative, neurological and muscular disorders. The study of neurodegenerative and muscular diseases includes various levels of investigation linked to molecular and cellular experimental models. Neuromuscular disease is a very broad term that includes many disorders that impair the functioning of muscles, either directly (pathologies of the muscle) or indirectly (pathologies of the nerves or neuromuscular junctions). In particular, DIMET addresses neurotransmission and excitation in the cerebral cortex, epilepsy, chronic processes of axonal degeneration, mitochondrial disorders and neurodegeneration with cerebral iron accumulation syndromes and other conditions.

• Neurotransmission and arousal in the cerebral cortex, epilepsy (Prof. Andrea Becchetti)
• In vitro and in vivo models of mitochondrial diseases and Neurodegeneration with Brain Iron Accumulation (NBIA) syndromes (Prof. Valeria Sonia Tiranti)
• Stress and neurosteroids in drug-resistant epilepsy. Prionic-like behavior of mutated SOD in ALS. Oxidative stress in multiple sclerosis and other neurodegenerative disorders. Protective activity of growth hormone secretagogues in Duchenne’s syndrome (Prof. Antonio Biagio Torsello)
• Role of genetic alterations in the development of epileptic encephalopathies (Prof. Ilaria Rivolta)
• Genetic alterations leading to myotonic dystrophies (Prof. Ilaria Rivolta)
• Nanoparticles for therapy of Alzheimer Disease and Glioblastoma (Prof. Francesca Re; Prof. Francesco Mantegazza)
• DNA-protein interactions, Abeta amyloid aggregation (Prof. Francesco Mantegazza)
• Epigenetic mechanisms involved in Emery Dreifuss Muscular Dystrophy (Prof. Chiara Lanzuolo)
• Single molecule analysis of protein folding and misfolding (Prof. Francesco Mantegazza)
• Lipidomic and Metabolomics in Neurodegenerative Diseases. Lipidomic effects of nanoparticles infused in Huntington Disease murine models (Prof. Valerio Leoni)
• Misfolding and aggregation of amyloid proteins (Prof. Carlo Santambrogio)
• Nano-omics approaches for biomarkers discovery in Alzheimer’s Disease (Prof. Claudia Corbo)
• Biomarkers and phenotyping in acute traumatic brain damages (Prof. Giuseppe Citerio)

3) Cardiovascular and pulmonary disorders. DIMET research programs in this field provide research experiences in the field of cardiovascular medicine, in order to train basic or clinical researchers with a solid background in biology and pulmonary and cardiovascular medicine, to apply latest generation technologies and models to the clinic's needs.

• iPS-derived cardiomyocytes, channel mutations and arrhythmogenic mechanisms; “late Na+ current” and cell damage (Prof. Antonio Zaza)
• New molecular and cellular mechanisms of cardiac arrhythmias causing sudden death; cardiomyocytes derived from induced pluripotent stem cells as experimental model for the study of cardiac arrhythmias (Prof. Ilaria Rivolta)
• Vascular biology/atherosclerosis and molecular aspects of plaque (Prof. Marialuisa Lavitrano)
• Mechanobiology: relationship between single cell nanomechanics and illness (Prof. Francesco Mantegazza)
• Lipidomic and metabolomic in cardiovascular diseases, Idiopathic pulmonary fibrosis and progressive fibrosing interstitial lung diseases (Prof. Valerio Leoni; Prof. Paola Faverio)

4) Immunological and infective disorders. Immunology influences nearly every aspect of modern medicine. The study of immunopathology and infectious pathologies is focused on the development of interdisciplinary research projects in cellular and clinical immunology and in innovative cellular approaches. Research interests in this area include host-pathogen interactions, immune surveillance, microbial pathogenesis and antibiotic resistance, vaccine development and immunotherapy.

• Triggering mechanisms of inflammation Host-pathogen interactions with specific interest in the role of dendritic cells (Prof. Francesca Granucci; Prof. Ivan Zanoni)
• How dendritic cells shape immune responses: multifaceted roles in health and disease (Prof Francesca Granucci)
• Differentiation of the myeloid compartment and its crucial role in homeostasis and disease (Prof Francesca Granucci)
• Stem cell-immune cell interaction: immune surveillance against self-renewing and differentiating stem cells (Prof Francesca Granucci)
• Chimeric T-cell receptor for the treatment of cancer patients (Prof. Andrea Biondi; Prof. Pietro Genovese)
• Adoptive Cell Therapy: Chimeric Antigen Receptor (CAR) -T cells   and Tumor Infiltrating Lymphocytes (TILs) for treatment of malignant gliomas (Prof. Serena Pellegatta)
• Innate immunity and skeletal muscle remodelling in genetic disorders (Prof. Silvia Brunelli)
• Innate immune signaling pathways in inflammatory disease development and progression (Prof. Ivan Zanoni)
• Xenotransplantation (Prof. Marialuisa Lavitrano)
• Lipidomic and metabolomic in SARS-CoV-2 disease (Prof. Valerio Leoni)
• Antimicrobial coating of medical devices (Prof. Laura Russo)
• Gender-dependent differential responses to therapies in intestinal diseases (Inflammatory bowel disease and colorectal cancer) (Prof. Federica Facciotti)

DIMET students find natural placement in public and private research centers, clinical centers of excellence, biomedical and biotechnological industries, both nationally and internationally. The expected career opportunities are those requiring interactions between basic and applied research and in contexts where "translational" professional profiles are required, with a solid background in basic research combined with the ability to transfer new knowledge to biomedicine to produce advanced diagnostic tools or innovative and effective therapeutic options. Professional figures such as researchers in academia, biotechnology companies, or within the healthcare system are opportunities available to those who have completed the DIMET doctorate.

The structure and programs of the DIMET Doctoral Course are based on the multidisciplinary nature of modern Biology and Medicine and the mutual need for biologists and medical professionals to familiarize themselves with medical and basic biology issues. The almost equal participation in training activities aimed at doctoral students by scientists from both basic and clinical research, and the organization of seminars for all students ensure productive interactions among the various components.

Teaching activities within DIMET develop starting from the skills and interactions in various research areas, both in broad areas of investigation (molecular and cellular mechanisms) and in more specialized contexts (neurological and neuromuscular diseases; oncology and hematology; infectious and immune diseases; pulmonary and cardiovascular diseases). Teaching emphasizes the translational approach in the transfer of skills, with application and further development in diagnostic or therapeutic research programs (clinical and regenerative medicine; technological platforms, nanomedicine, and diagnosis). The proposed doctoral programs will take place in an advanced biotechnological context.

Teaching activities can be consulted on the e-learning platform