Translational Medicine

Dottorati
Doctoral programme (PhD)
A.Y. 2024/2025
Study area
Medicine and Healthcare
Doctoral programme (PhD)
3
Years
Dipartimento di Scienze biomediche per la salute - Via Mangiagalli, 31 - 20133 Milano
English
PhD Coordinator
The doctoral programme aims to train researchers who are able to develop research projects that bridge the gap between laboratory activity and clinical sciences, facilitating the translational process in both directions.
Aims:
1. understand and study biological structures in the different levels of organisation, their physiological and pathological modifications in the framework of interactions between people and the environment, exploring diagnostic and therapeutic interventions and facilitating their application in clinical practice;
2. learn a scientific translational research approach which can favour points of contact between biological and clinical-behavioural discoveries and preventive, therapeutic and rehabilitation practices in order to improve di health and lifestyle, also considering the global increase in life expectancy;
3. acquire a solid preparation in the methodological disciplines required to formulate correct experimental hypotheses, define experimental designs and critically interpret results;
4. promote communication between biological and clinical-behavioural research, particularly in relation to movement and physical activity in the area of prevention, mental-physical wellbeing, sport and professional performance, in conditions of health, illness and disability, in a unified perspective;
5. understand the ethical implications of clinical and biological research.
Tutte le classi di laurea magistrale - All classes of master's degree
Dipartimento di Scienze biomediche per la salute - Via Mangiagalli, 31 - 20133 Milano
Title Professor(s)
Dissetting the molecular mechanism that links loss of lysosomal function with the onset of neurodegeneration and development of new therapeutic strategies
Requirements: Experience in cell culture
Lipid-based therapeutic strategies to optimize the effectiveness of innovative drugs to rescue mutated CFTR
Requirements: Experience in cell culture
Recent studies underlined the importance of an integrate evaluation of the dynamics of interaction among heart, brain and peripheral systems. The project will be aimed to jointly investigate cortical-autonomic-vascular dynamics and to develop a quantitative framework describing the interactions among the different physiological systems in physiological conditions and in critical situations.
Requirements: Expertise in biomedical signal processing and statistics.
Study of the dominance effect of cardiac Na channels mutations associated with arrhythmic diseases
Requirements: Knowledge of cell biology and/or molecular biology and/or electrophysiology and/or biophysics
Molecular mechanisms of host–parasite interactions in cutaneous Leishmaniasis: new in vitro 2D-3D models to unveil the role of macrophages, keratinocytes, and endothelial cells in the establishment of infection at the site of inoculum
Requirements: Basic Knowledge of cellular and molecular biology
Pathogenic implications of viral co-infections. In vitro models to study immunological, molecular and epigenetic determinants.
Requirements: Knowledge of basic 2D and 3D cellular cultures.Omics approach to investigate biomarkers of disease susceptability/progression
Next-generation sequencing and single-cell transcriptomics in characterizing clonal cell populations and immune microenvironment in multiple myeloma. Requirements: knowledge of molecular biology protocols, NGS, and their respective analysis techniques
N. Bolli
Role of Extracellular vescicles in microbial biofilms
Requirements: Basic knowledge of Microbiology
Microbiota-gut-brain axis in neurological diseases
Requirements: Basic knowledge of molecular Biology
Molecular and phylogenetic approaches for studying pathogens with a high social and health burden
Requirements: Basic knowledge of Microbiology and Molecular Biology
This research program will provide basic knowledge of neuroimaging, omic, neurotransmitter and neurocognitive bases of the major psychiatric illnesses, such as psychotic, mood and anxiety spectrum disorders, with particular regards to brain connectivity and prefronto-limbic neuropsychological, omic, and neuromodulatory dimensions. Examples will be provided on how neurosignal (brain MRI, PET, TMS, fNIRS, EEG), neurophysiological, omic, neuropsychological and virtual reality multimodal multisource measures need to be analysed and integrated, and how they can be translated into clinical knowledge for assessment of pathophysiology, diagnosis, prognosis, and clinical outcome of those major psychiatric disorders.
Requirements: Basic knowledge of Machine Learning techniques and of coding languages (Matlab or R); and of brain imaging
Biomarkers associated with the diagnosis of Schizophrenia and Mood Disorders: epigenetic, inflammatory and hormonal factors involved in the etiology and outcome of these psychiatric conditions
Requirements: Competence in the field of translational research (including mental health assessment) and/ or in the field of molecular biology
Interplay between endothelial cells and C1INH in the pathophysiology of HAE. Hereditary angioedema due to C1-inhibitor deficiency (HAE) is a rare and potentially fatal autosomal dominant disease characterised by localized edema of the subcutaneous and submucosal tissue. It can be considered the paradigm of Paroxysmal Permeability Diseases (PPDs), pathological conditions characterized by sudden, recurrent, but reversible increase of endothelial permeability without inflammatory, degenerative or ischemic injury.
Requirements: Basic knowledge of cellular and molecular biology.
Mucosal tissue homeostasis is the result of the balance achieved by immune cells, the epithelium and the microbiota inhabiting the mucosae. Alterations in the composition and function of the microbial ecologies and of the immune responses has been associated to different pathologies, including inflammatory bowel disease (IBD). Approaches targeting either the immune system functions or the composition of the gut microbiota are being proposed to provide durable therapeutic options to IBD patients. However it is still lacking the piece of knowledge needed to restore tissue homeostasis by modulating the functions of specific immune system’s populations through rationally modified microbial ecologies. The goal of this project is to propose a novel approach to modulate the functions of mucosal T cells through the rational generation of microbial ecologies (MMEs) specifically designed to promote anti-inflammatory and tissue restituting activities of T cells in vivo.
Requirements: Ability to work with eukaryotic and prokaryotic cells. preferred: background in cellular immunology and microbiology. Experience with human primary cells
Role of extracellular vesicles (EVs) in modulating pathological processes
Requirements: Knowledge of the main biochemistry and molecular biology techniques; ability in handling cultured cell line models.
(Sphingo)lipid dysmetabolism and primary hepatic cancer
Requirements: Knowledge of the main biochemistry and molecular biology techniques; ability in handling cultured cell line models.
Novel syndromic alterations associated with the glycosphingolipid dismetabolism
Requirements: Knowledge of the main biochemistry and molecular biology techniques; ability in handling cultured cell line models.
M. Trinchera (UnInsubria)
Motor Learning and relearning in neurological conditions
Requirements: The candidate should have knowledge of physiological mechanisms of the central nervous system. Furthermore, she/he should be familiar with pathology-induced effects of neurological disorders on the sensory-motor system.
Central organization of the postural control associated with voluntary movement, either in healthy subjects or in patients affected by movement disorders.
Requirements: In-depth knowledge of the physiology of movement and posture in humans. Use of programming and data processing software.
Sympatho-vagal balance and physical exercise.
Requirements: In-depth knowledge of the exercise physiology in humans. Use of programming and data processing software.
Analysis of cerebral motor resinace evoked by linguistc and/or visual stimuli in humans.
Requirements: In-depth knowledge of sensory-motor systems physiology in humans. Use of programming and data processing software.
Disfunzioni mitocondriali nella malattie neurodegenerative: ruolo dei glicosfingolipidi
Requirements: Experience in the biochemical and molecular biology field is required. Skills in cell cultures, analysis of sphingolipid content and metabolismm, and analysis of protein content are also required
Role of inflammasome and phagocytosis in the pathogenesis of neurodegenerative diseases (Alzheimer Disease, Multiple Sclerosis, Parkinson Disease).
Requirements: Knowledge of cellular and molecular immunology
In vivo human studies of exercise-stimulated metabolism to elicit anti-inflammatory and immunomodulatory responses in dysmetabolic conditions. In particular, it wil be covered: incremental exercise testing in normal weight, overweight/obese subjects, and athletes - measurements, clinical indications, and metabolic determinants related to energy metabolism.
Requirements: Good knowledge of the anatomical and physiological aspects of neuro-endocrine-muscular systems.
Study of Molecular Mechanisms Involved in the Etiopathogenesis of Neurological Disorders
Requirements: Knowledge and experience in cellular and molecular biology
Development of cellular and molecular therapeutic approaches for neurological diseases
Requirements: Knowledge and experience in cellular and molecular biology
Molecular and cellular mechanisms of pathogenesis of vascular calcification in uremia
Requirements: Cell culture, Western-blot, Real time PCR
Immunomodulatory activity of vector-borne, protozoa parasites (Malaria & Leishmania) and their products on macrophages, microglia, and endothelial cells from different anatomical origins: implication for the pathogenesis and establishment of chronic infections.
Requirements: Basic Knowledge of cellular and molecular biology
Study of infectivity and severity of respiratory viruses based on isolated variants
Requirements: Basic Knowledge of cellular and molecular biology
Study of the possible involvement and mechanism of actions of Human Endogenous Retroviruses in the colon cancer pathogenesis
Requirements: Basic Knowledge of cellular and molecular biology
Effects of microplastics on the immune system and on inflammatory processes
Requirements: Knowledge of cellular and molecular immunology
Advanced thyroid cancer: primary cultures and 3D cells models to study new drugs
Requirements: Cell cultures, transfection assays, confocal microscopy, proliferation and apoptosis assays, Western blot, sequencing
Application of deep learning in predictive molecular pathology to improve cancer diagnosis and biomarker testing. By developing and training deep learning models on histopathology and molecular data such as genomics, proteomics, and transcriptomics, we aim to improve diagnostic accuracy, predict disease progression, and personalize therapeutic approaches. Key activities include data collection and preprocessing, model development, training and validation, and ensuring model interpretability. Collaboration with pathologists and oncologists will be part of the everyday activities.
Requirements: Bioinformatic skills
Characterization of the effect extracellular matrix components, tumor microenvironment and 3D arrangement on epithelial-to-mesenchymal transition and carcinoma progression
Requirements: Knowledge of cell and molecular biology
Study of collagen turnover and expression of genes and proteins involved in extracellular matrix remodeling in connective tissue in physiological and pathological conditions, and after pharmacological treatment
Requirements: Knowledge of cell and molecular biology
Targeting defects in mitochondrial functions by exploiting human cellular and yeast models
Requirements: The project involves functional and transcriptomic analyzes on cellular models. Experience in NGS/RNAseq and knowledge of molecular and cellular biology is required.
Immuno-signatures as biomarkers in mitochondrial diseases: from clinical trials to new therapeutic prospective
Requirements: Experience in the field of mitochondrial medicine. Experience in immunological analysis and molecular biology techniques.
C. Lamperti (Istituto Neurologico Besta)
Morphological and metrical analysis of the skeleton: study of the biological variability in clinical, surgical and anthropological fields
Requirements: Basic information of osteology
Sphingolipid metabolism and signaling as a therapeutic target in tumor cells. The research project aims to study sphingolipid-mediated signal transduction mechanisms in physio-pathological processes with the aim of identifying targets for the development of innovative and effective therapies against tumors. In particular, the metabolism and the functional properties of specific sphingoid mediators will be investigated in the tumorigenicity of tumor and /or cancer stem cells.
Requirements: Basic knowledge of the experimental procedures used in a biochemical research laboratory
Evaluation of Exercise Performance
Requirements: Basic physiology
Environmental and genetic factors strongly influence the pathogenesis and evolution of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The project will evaluate the impact of genetic variants, epigenetic modifications and nutritional intake on liver damage, mitochondrial dysfuntion and cardiovascular comorbidities in patients with histological diagnosis of NAFLD, in in vitro models and in mouse models of hepatic steatosis. The study will be implemented with omics techniques (spatial transcriptomic, single cel transcriptomic, lipidomic, proteomic) that will allow to define non-invasive markers for the identification of patients at risk of progressive disease.
Autonomic nervous system assessment to optimize training in elite athletes and to optimize exercise prescription for cardio‐metabolic and cancer treatment/prevention
Requirements: Knowledge at introductory level of exercise physiology, elements of physiology of autonomic nervous system and etiopathogenetic mechanisms of cardio‐metabolic diseases and cancer
Lifestyle (focusing mainly on physical exercise) as sustainable tool for individual, environment and society, fostering wellbeing and reducing cardiometabolic risk factors
Requirements: Knowledge at introductory level of etiopathogenetic mechanisms of chronic diseases (cardio‐metabolic diseases and cancer) and of basic clinical aspects
Epicardial fat: From the biomolecular aspects to the clinical practice
Thyroid and adrenal cancers: Studies on clinical aspects, prognostic risk factors, new biomarkers and innovative treatments .
Manipulation of insulin receptor (IR) alternative splicing as a novel therapeutic strategy to block IGF2 autocrine proliferative loop in adrenocortical carcinoma
Requirements: Cell cultures; cell transfection and silencing; protein detection (western blot, co-/immunoprecipitation); nucleic acid extraction, PCR.
Cell senescence and neurodegeneration
Requirements: Knowledge of the main molecular and tissue culture techniques
Cell comunication in the pathological pulmonary microenvonment of lymphangioleiomyomatosis: characterizaton of the secretome and extracellular vesicles
Requirements: Knowledge of the main biochemical and molecular biology techniques; tissue culture experience.
Inflammation and obesity: analisys of plasma sphingolipid biomarkers by mass spectrometry
Requirements: Previous laboratory experience with knowledge of the main biochemical techniques
Nanotechnological approaches for diagnosis, treatment and management of cancer
Requirements: Cell biology skills for the management of immortalized human or mouse cell lines. Knowledge of the main biochemical techniques . Knowledge in mice handling and murine model development for in vivo studies (if possible).
Patient-derived organoid of breast cancer: development, characterization and application in tumor biology studies
Requirements: Manipulation of tumor cell lines. Knowledge of the main biochemical and cell biology techniques.
Contrasting body deconditioning due to prolonged low gravity exposure: from M-WALL countermeasure optimization to effect check via Bed Rest campaigns
Requirements: Basic knowledge in biomechanics and IT
Study of the antitumor role of different natural compounds in "in vitro" models of human cancers and the molecular mechanisms involved, in order to identify new molecular targets for future therapeutic strategies.
Requirements: Basic knowledge in cell cultures, and in cellular and molecular biology
Aging in thalassemia in the era of new treatments New treatments are changing the natural history of thalassemia with more prolonged survival and new emerging complications and comorbidities. Studying the peculiar aspects of aging in thalassemia is crucial to establishing a tailored follow-up and personalized management.
Requirements: Documented experience in the field.
Therapeutic strategies for neurological involvement in Gaucher disease Approved treatments for Gaucher disease do not cross the blood-brain barrier and do not impact the natural history of neurological involvement. Identifying potential disease modifiers for the neurological aspect of Gaucher disease is crucial for patients' management.
Requirements: Documented experience in the field.
Molecular diagnosis of infectious diseases from histological tissues using new technologies
Requirements: Basic knowledge of molecular biology; Basic knowledge of histopathology
Assessment of the role of CMA in resistance to treatment in Glioblastoma. CMA is a mechanism of degradation of proteins containing a specific consensus sequence demonstrated to play a pivotal role din responsiveness to treatment in glioblastoma (GBM). Post translation modifications, can create or eliminate such recognition motifs by modulating the panel of potential targets producing different consequences. The activation of this mechanism has been demonstrated to be fundamental in mediating the responsiveness of different tumors to specific treatments. The molecular mechanisms behind its regulation are not fully understood, as is its role both in physiology and pathology. Within the research project, particular attention will be paid to the modulations of the "targetome" of this specific mechanism of degradation and its regulatory role. The correlation of this mechanism with metabolic modulations related to the responsiveness to treatment will be studied. Evaluations will be carried out in pairs of syngeneic GBM cell lines (sensitive and resistant) and in samples derived from patients. Samples obtained from patients undergoing surgical treatment, will be used to assess a panel of biomarkers related to the activity of the CMA whose modulation has been found to be able to predict early response to specific treatments as part of a personalized medicine approach. The role of some miRNAs and potential new drugs already identified as treatment response regulators and related to CMA activity will also be studied in view of the development of new nucleic acid-based therapeutic approaches. Innovative non-invasive imaging techniques will be used in orthotopic animal models of GBM to follow key processes in the living model over time. Fully equipped cell and molecular biology laboratories, an animal care facility and the Perkin Elmer’s top-of-the-line optical imaging device (IVIS-Spectrum/CT) will be available for such research project.
Requirements: Requirements: Knowledge of the basic elements of molecular oncology and tumour metabolism. Basic knowledge of pharmacology, cell biology, use of organoids and molecular biology techniques.
Drug discovery for vector borne, poverty-related, emerging parasitic diseases, malaria and leishmaniasis: identification of novel potential antiparasitic compounds and their mechanisms of action to overcome the problem of resistance.
Requirements: Basic Knowledge of cellular and molecular biology
Biomechanics and bioenergetics of human movement and locomotion, also in simulated hypogravity
Requirements: Knowledge of muscle and locomotion physiology and biomechanics; skills in data analysis also with purposely written software
Respiratory physiology and pathophysiology investigated with advanced diagnostic techniques. In particular role of the small airways in the development and manifestation of pulmonary diseases, with reference to the effects of small airways cyclic opening and closing in patients and in animal models.
Requirements: Knowledge of respiratory physiology, biophysics and/or biomechanics.
Network Physiology (NP) is an emerging field of computational physiology that allows to study the cardiovascular and cerebrovascular regulatory systems and their dynamical interactions. The project will evaluate associations between the functioning of physiological control mechanisms, as assessed via typical NP methods before major cardiac surgery, and the development of postoperative cardiovascular and cerebrovascular adverse events.
Requirements: Expertise in biomedical signal processing and statistics.
An impairment of the cardiac neural control during physical exercise and recovery phase can expose the subject to the risk of arrhythmic events. The project will use advanced time series analysis techniques for the indirect assessment of the cardiac neural control during maximal physical exercise and the return to baseline situation.
Requirements: Expertise in biomedical signal processing and statistics.
Cerebrovascular autoregulation is a fundamental mechanism for maintaining adequate cerebral perfusion in the presence of blood pressure changes. The autonomic nervous system plays an important role in the regulation of vascular resistances. The project will use advanced signal processing techniques to characterize the interaction between the autonomic nervous system and cerebrovascular autoregulation in physiological conditions and in critical situations.
Requirements: Expertise in biomedical signal processing and statistics.
Role of sphingolipids in the mechanism of repair of damaged myelin, with focus on multiple sclerosis.
Requirements: Knowledge of the basics of sphingolipid biochemistry. Knowledge of the techniques of cell culture and of basics of cellular and molecular biochemistry techniques.
3D Bioprinting technology from the development of tissues and organs to in vitro models.
Requirements: Knowledge of basic techniques for cell cultures, optical and fluorescence microscopy.
Evaluation of advanced parameters of cardiac MR in elderly patients
1.Study of electrostimulation in cellular models and of electrostimulation therapy in patients with neurodegenerative disorders 2. Metabolic Signatures of Cardiac Dysfunction, in ischemic or Valve stenosis patients.
Single Cell Analysis for biomolecular and matobolomic pathways discovery
Requirements: Knowledge of in vitro and in vivo cellular and molecular biology.
P. Mauri (CNR)
C. Villa
The role of Immune Checkpoints in trasplants: the pathways of rejection and new therapeutic prospectives
Requirements: Knowledge of cellular and molecular immunology with omics approaches
V-ATPase at the crossroad of epigenetics and bioenergetics in glioma stem cells
Requirements: expertise in cellular biology possibly with primary/3-D cultures; basic knowledge of NGS, RNAseq, epigenetics and data analysis
Dario C. Altieri (The Wistar Institute, Philadelphia USA)
Role of extra-cellular vesicles from bronchoalveolar lavage fluid in the lung microenvironment of lung transplanted patients
Requirements: expertise in cellular biology possibly with primary cultures; basic knowledge of NGS, RNAseq and data analysis
Identification and evaluation of the genetic mechanisms underlying liver disease development to develop precision medicine approaches
Requirements: Previous research experience in clinical or basic hepatology, or genetics/molecular biology or bioinformatics/computational sciences
Extracorporeal supports for ex-vivo and in-situ organ perfusion. Optimization and development of extracorporeal supports for the evaluation and reconditioning of solid organs before transplantation
Requirements: Good knowledge of human physiology and supports for organ perfusion
Otimization of mechanical ventilation in patients during cardiac arrest
Requirements: Good knowledge of human physiology
MicroRNAs as Potential Predictive Biomarkers for Prognosis and Rehabilitation Outcome in Neurodegenerative Diseases (ex DM 630/2024)
Requirements: Molecular and cellular biology expertise
R. Mancuso (Fondazione don Gnocchi)
Validation of innovative biophotonic methods for the differential diagnosis of chronic pulmonary diseases (ex DM 630/2024)
Requirements: The applicant is required to have: - good theoretical knowledge of the physical principles of the biophotonics techniques - experience in the analysis of biological samples using Raman Spectroscopy and Surface Plasmon Resonance for biomedical applications, in particular in the field of pulmonary diseases - experience in data analysis using Artificial Intelligence algorithms - experience in the isolation and characterization of extracellular vesicles from biological samples - good ability to handle liquid biopsies such as saliva and blood, and knowledge of the operating methods for the evaluation and management of the associated risks
M. Bedoni (IRCCS Fondazione Don Gnocchi Milano)
Development of customized dental devices such as on-site 3D-printed biodegradable orthodontic aligners for detecting predictive biomarkers of neurodegenerative diseases (ex DM 630/2024)
Requirements: Extensive computer knowledge
E. Sidoti (Studio SST s.r.l.)

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Places available: 21

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Application for admission: from 29/05/2024 to 27/06/2024

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