Supervisor: Prof. Matteo Marti

Co-supervisor: Prof. Fabrizio Vincenzi

Project Title: Evaluation and Correlation of the Pharmacokinetic Profile and Pharmacotoxicological Effects of New Psychoactive Substances

Project Description: New Psychoactive Substances (NPS) are synthetically or semi-synthetically designed compounds intended to evade the controls placed on traditional drugs (such as cannabis, cocaine, LSD), while mimicking their effects. The circulation of NPS poses a significant public health risk, as information about their pharmacotoxicological and pharmacokinetic profiles is limited. This project aims to evaluate the neurological, behavioral, and physiological effects of NPS reported by the Department for Anti-Drug Policies (DPA) of the Prime Minister’s Office, and correlate them with their pharmacokinetic properties using various experimental approaches and preclinical models (zebrafish larvae and mouse models).

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Supervisor: Prof. Stefania Gessi

Co-supervisor: Prof. Stefania Merighi

Project Title: Identification of the A2A Adenosine Receptor in Human Platelets as a New Peripheral Biomarker for the Diagnosis of Alzheimer's Disease

Project Description: Alzheimer's Disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia in the elderly population of developed countries, characterized by a progressive decline in cognitive functions. Early diagnosis, which is crucial for therapeutic intervention, is currently complex, costly, and invasive. The aim of this project is to develop a simple and cost-effective diagnostic method by evaluating the expression of the A2A adenosine receptor in the platelets of AD patients, comparing it with that found in post-mortem brain samples. The goal is to determine whether A2A expression in platelets can reflect changes in the central nervous system, suggesting its role as a peripheral biomarker for the early diagnosis of AD.

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Supervisor: Prof. Angelina Passaro

Co-supervisor: Prof. Sergi Domenico

Project Title: Study of Postprandial Hyperlipidemia in the Search for New Strategies for Diagnosis, Prevention, and Treatment of Type 2 Diabetes Mellitus and Its Complications: New Organizational Models in Research (From the Community to the Laboratory)

Project Description: The project, aligned with the objectives of the Italian National Recovery and Resilience Plan (PNRR) Mission 4, Component 2, Investment 3.3, aims to study the postprandial phase and the determinants of progression from insulin resistance to complicated T2D as a pilot example to promote synergistic collaboration between basic research, clinical healthcare facilities, and community medicine. The goal is to create a cooperative model based on knowledge, accessibility, and reusability of research results, leveraging innovative digital technologies and new collaboration tools to effectively address the complex challenges posed by T2D. The project seeks to clarify the mechanisms involved in the transition from prediabetes to T2D and improve public health outcomes.

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Supervisor: Prof. Roberta Rizzo

Co-supervisor: Prof. Elisabetta Caselli

Project Title: Identification of Cellular Pathways Involved in the Effect of Flavivirus sNS1 Proteins on Key Host Biological Processes

Project Description: The project investigates the biological processes disrupted during infections by emerging viruses such as Coronaviruses and Flaviviruses, which are associated with vascular and coagulation disorders. It focuses on studying the role of viral proteins like SARS-CoV-2 PLPro and Flavivirus NS1. The specific effects of these proteins and their impact on biological disorders will be examined, analyzing inflammatory and immune markers. In vitro models will be employed to study coagulation factors, RNA sensor pathways, cytokines, and HLA-G. The aim is to understand the immune and coagulative mechanisms involved, providing a foundation for the development of new targeted therapies.

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Supervisor: Prof. Peggy Carla Raffaella Marconi

Co-supervisor: Prof. Antonella Caputo

Project Title: Therapeutic Strategies for the Treatment of Spinocerebellar Ataxia Type 1 and Type 2

Project Description: Spinocerebellar ataxias type 1 (SCA1) and type 2 (SCA2) are autosomal dominant neurodegenerative diseases caused by mutations in the ATXN1 and ATXN2 genes, which produce toxic proteins with polyQ expansions. Symptoms, including ataxia, dysarthria, and neuropathy, typically manifest between the ages of 30 and 40, with an average life expectancy of 10-20 years from symptom onset. This project combines CRISPR/Cas9 gene-editing technology to silence the mutated genes with drug repurposing approaches to stimulate protein degradation. Using 3D models of patient-derived induced neurons, the molecular mechanisms underlying the disease are studied, and innovative therapies are tested. The aim is to address both the genetic causes and neurotoxicity of these conditions.

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Supervisor: Prof. Daria Bortolotti

Co-supervisor: Prof. Roberta Rizzo

Project Title: Characterization of Viral Vectors Using Innovative Nanopore Technology

Project Description: Gene therapy using adeno-associated viral (AAV) vectors holds great promise for the treatment of numerous genetic disorders. However, the effectiveness and safety of these therapies require precise characterization of the viral particles. The project involves the development of a prototype, in collaboration between the company Elements Srl and the University of Ferrara, based on solid-state nanopore resistive pulse sensing technology for a rapid, reliable, and cost-effective assessment of the presence, size, and genetic cargo of AAV particles. The project aims to train a specialist in the use of advanced technologies for the characterization of viral vectors.

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Supervisor: Prof. Annalisa Marcuzzi

Co-supervisor: Prof. Rebecca Voltan

Project Title: Study of Innovative Therapeutic Strategies for the Treatment of Colon Carcinoma

Project Description: The primary goal of my PhD project will be to evaluate the antitumor activity of substances extracted from plant sources as adjuvants to chemotherapy in preclinical experimental models designed to mimic the pathological conditions typical of colon carcinoma. In addition to classical cell culture techniques, the study may also include the use of 3D cell models capable of mimicking the intestinal epithelium in vitro. The research may also involve molecular conjugates, micro-encapsulated compounds, or molecules loaded onto nanoparticles formulated to enhance intestinal uptake, bioavailability, and efficacy compared to the original molecules.

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Supervisor: Prof. Carlo Cervellati

Co-supervisors: Prof. Alessandro Trentini, Prof. Giovanni Zuliani

Project Title: Blood-based Biomarkers in Neurological Diseases

Project Description: The PhD project involves the study of potential biomarkers for the diagnosis of chronic and progressive neurodegenerative diseases such as Alzheimer’s disease. Specifically, the focus will be on assessing the activity and concentration of β-secretase (BACE1) and α-secretase (ADAM 9-10), two enzymes of critical importance for the development and progression of the disease. The study will be conducted on serum and various regions of post-mortem human brain tissue from patients with Alzheimer’s disease (AD) and Mild Cognitive Impairment (MCI), employing various methodologies, including electrophoretic techniques (Western Blot), ELISA assays, and conventional spectrophotometric and spectrofluorometric enzymatic assays. Another objective will be to evaluate BACE1 activity in cerebrospinal fluid (CSF) from AD/MCI patients, correlating it with the concentration of other molecules involved in this complex pathological state, such as Aβ42-40-34.

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Supervisor: Prof. Marco Pellegrini

Co-supervisor: Prof. Diego Ponzin

Project Title: New Methods for the Preservation of Ocular Cells and Tissues for Transplantation

Project Description: The research project focuses on three objectives to improve corneal transplantation. First, to develop new preservation media to enhance the vitality and quality of tissues. Second, to integrate artificial intelligence for the objective evaluation of key parameters such as endothelial density and morphology, reducing the subjectivity of operator assessments. Third, to design advanced surgical devices that optimize surgical procedures and minimize cell mortality. The overall goal is to optimize processes, evaluations, and interventions in eye banks, improving the quality of transplanted tissues and ensuring better surgical outcomes for patients.

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Supervisor: Prof. Luca Lombardo

Co-supervisor: Prof. Dorina Lauritano

Project Title: 3D Printing of Orthodontic Devices

Project Description: The project aims to study the 3D printing of orthodontic devices. A key objective is to expand access to orthodontic treatments by introducing these innovative printed devices. This advancement makes treatments more accessible, both economically and practically, enabling a larger population to benefit from orthodontic care. Another goal is to reduce production costs across the entire supply chain wherever possible.

The use of differential thicknesses in printed materials marks a significant improvement over traditional thermoformed aligners. These differentiated thicknesses allow for the application of variable biomechanical forces, better adapting to the specific needs of each tooth and zone of the dental arch. Furthermore, the porosity of certain printed materials opens new possibilities in dental prevention.

In summary, the introduction of 3D-printed orthodontic devices not only makes treatments more affordable and accessible but also offers significant advancements in biomechanical efficiency and cavity prevention, representing a major step forward in the field of orthodontics.

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Supervisor: Prof. Alberto Papi

Co-supervisor: Dr. Federico Baraldi

Project Title: Biomarkers and Clinical Markers in Response to Treatment in Severe Obstructive Respiratory Diseases

Project Description: Severe obstructive respiratory diseases (Asthma and COPD) are among the leading causes of death and disability. Patients suffering from these conditions often experience symptoms that are difficult to control and a poor quality of life. Recent therapeutic approaches have highlighted the significant heterogeneity of these diseases, both biologically and clinically, compelling researchers to investigate the factors that must be considered to ensure a diagnostic and therapeutic approach tailored to each patient's unique characteristics.

Our project focuses on identifying and studying potential biomarkers useful for predicting or monitoring the response to therapy in patients with severe respiratory diseases.

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Supervisor: Prof. Massimo Busin

Co-supervisor: Dr. Angeli Christy Yu

Project Title: Predicting Intraoperative and Postoperative Outcomes in Deep Anterior Lamellar Keratoplasty Using Artificial Intelligence

Project Description: The aim of this study is to develop and validate a Deep Learning (DL) model to predict intraoperative and postoperative outcomes in eyes undergoing deep anterior lamellar keratoplasty (DALK) for keratoconus. A multimodal DL convolutional neural network model will be used to analyze tomographic images of the cornea and topographic maps of eyes undergoing DALK with the "big-bubble" technique.

The study plans to enroll 1,000 patients. The primary endpoint is the area under the receiver operating characteristic curve (AUC) for predicting bubble formation during DALK surgery. Secondary endpoints include the AUC of DL models for predicting (micro)perforations and postoperative outcomes such as best spectacle-corrected visual acuity (BSCVA), refractive astigmatism, and topographic cylinder.

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Supervisor: Prof. Paola Secchiero

Co-supervisor: Dr. Eva Reali

Project Title: Innovative Immunological Therapies for Chronic Inflammatory and Autoimmune Diseases

Project Description: During the first year of my PhD, I will focus primarily on a murine model of psoriasis, a chronic inflammatory skin disease characterized by cutaneous and articular manifestations and associated with systemic comorbidities such as metabolic syndrome and cardiovascular diseases. Psoriasis arises from an interplay between genetic predisposition and environmental factors, yet the mechanisms linking these factors to the immune response in the skin remain poorly understood.

I will explore innovative therapeutic strategies, such as inflammasome inhibition and the use of nanoparticles to limit the recirculation of inflammatory cells. The aim is to improve skin manifestations and reduce systemic complications.

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Supervisore: Prof.ssa Elisabetta Melloni

Co-supervisore: Prof.ssa Erika Rimondi

Titolo progetto: Identificazione di nuovi target cellulari e di strategie terapeutiche innovative per il trattamento di patologie degenerative retiniche

Descrizione progetto: Il progetto ha come obiettivo la valutazione dei potenziali effetti terapeutici di nuovi approcci farmacologici per patologie degenerative della retina caratterizzate da un ampio coinvolgimento della componente vascolare, come la retinopatia diabetica e la degenerazione maculare senile, e per le quali, attualmente, il trattamento di prima linea è rappresentato dalla somministrazione intravitreale di farmaci anti-angiogenici, possibile causa di gravi effetti collaterali. Dal momento che è ormai chiaro che, tra le cellule coinvolte nel mantenimento dell’omeostasi vascolare retinica, quelle dell’epitelio pigmentato retinico svolgono un ruolo chiave, il progetto verrà sviluppato su modelli preclinici di tale epitelio, nuovo target terapeutico.

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Supervisor: Prof. Nicoletta Bianchi

Project Title: Omics and Biomarkers in Personalized Cancer Therapy

Project Description: This project adopts a bioinformatics approach to analyze and identify molecular targets for diagnosis or the development of new therapies, with a particular focus on breast cancer, specifically the triple-negative phenotype. The approach leverages next-generation sequencing techniques, including single-cell transcriptomics, which enable the study of tumor cell heterogeneity.

To process the vast amount of data, analytical methods such as machine learning are employed, coupled with the computational power of graphic processing units (GPUs). This allows for an innovative and personalized approach in the field of oncology.

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Supervisor: Prof. Domenico Sergi

Project Title: Effects of the Lipid Cargo of Extracellular Vesicles Derived from Adipocytes on the Metabolic Crosstalk Between Adipocyte-Macrophage-Skeletal Muscle

Project Description: The content of extracellular vesicles (EVs) secreted by hypertrophic and dysfunctional adipose tissue represents one of the links between obesity and its comorbidities. However, it is not yet known whether energy overload can reshape the lipid cargo of EVs and whether this cargo mediates the effects of adipocyte dysfunction on the activation of the immune component of adipose tissue and the energy metabolism of other tissues, including skeletal muscle.

The aim of this research project is to investigate the metabolic effects of the lipidome of EVs derived from dysfunctional human adipocytes on macrophage activation and polarization, as well as on the insulin sensitivity of skeletal muscle.

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Supervisor: Prof. Gianluca Campo

Project Title: Standardization of the Management of Patients with Coronary Microvascular Dysfunction: The SAMCRO Study

Project Description: The goal of the SAMCRO study is to evaluate whether a multidimensional lifestyle intervention improves angina status and quality of life in patients with angina and no obstructive coronary artery disease (ANOCA), compared to current standard management.

This is a prospective, randomized, multicenter, open-label study open to all eligible patients. Patients with coronary microvascular dysfunction or coronary vasomotion disorders will be enrolled. At least 120 patients with ANOCA will be randomized into two groups: multidimensional lifestyle intervention vs. standard management. The primary endpoint is the improvement in angina status, assessed using the validated Seattle Angina Questionnaire (SAQ) after one year.

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Supervisor: Prof. Massimiliano Castellazzi

Project Title: Multivariate Approach to the Use of Biomarkers for Neuroinflammation and Neurodegeneration

Project Description: This research project investigates the role of diagnostic and prognostic biomarkers of neuroinflammation and neurodegeneration in cerebrospinal fluid and serum in patients with various neurological disorders. The main objective is to identify potential sex-related differences to develop sex-specific cut-off values, thereby improving diagnostic accuracy and enabling personalized therapeutic approaches.

The project adopts a multivariate approach to integrate laboratory data with clinical and demographic information, supporting precision medicine.

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Supervisor: Prof. Erika Rimondi

Co-supervisor: Dr. Diego Ponzin

Project Title: Advances and Innovations in Biobanking Practices

Project Description: The project aims to contribute to advancements and innovations in biobanking practices through four key objectives: 1.Development of a SMILE Stromal Lenticule Biobank (main project): In the first year, I characterized SMILE lenticules by evaluating preservation methods (dehydration, cryopreservation with DMSO or glycerol). In the second year, I will complete the characterization, identify the best method for clinical preservation, and request authorization from the National Transplant Center (CNT) to establish an official biobank. Additionally, I will explore their use as drug delivery systems and as alternatives to allogenic stromal rings (CAIRS), providing biocompatible solutions for keratoconus treatment. Methodologies include OCT, transparency testing (validated device), histological analysis, immunofluorescence, and TEM. 2.Development of a Stromal Ocular Lens Biobank: This project aims to optimize preservation techniques for unused lenses in laboratories. I will evaluate transparency, cell viability, RNA stability, and structural integrity by comparing fresh and preserved lenses using immunofluorescence, histological analysis, and PCR. 3.Development of New Corneal Preservation Media:In the first year, I compared a synthetic medium with a commercial medium containing animal serum. I will conclude the study, aiming for CE certification and commercialization of the synthetic medium, which ensures greater safety and ethical standards. 4.Improving Endothelial Cell Viability in Pre-loaded Tissues for DMEK: I will examine techniques to reduce cellular damage during the loading and insertion of DMEK tissues, using Trypan Blue and Calcein staining to assess cell mortality, morphology, and density.

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Supervisor: Prof. Gianluca Campo

Project Title: Transcatheter Aortic Valve Implantation With or Without On-Site Cardiac Surgery: The TRACS Study

Project Description: The TRACS study is a prospective, randomized, multicenter trial aiming to enroll 566 inoperable or high surgical risk patients with severe aortic stenosis indicated for TAVI. Current guidelines recommend that TAVI be performed only in centers with on-site cardiac surgery (CS).

Patients will be randomized to receive TAVI either in centers without on-site cardiac surgery or in centers with on-site cardiac surgery. The primary endpoint is to determine whether TAVI performed in centers without on-site cardiac surgery is non-inferior to TAVI performed in centers with on-site cardiac surgery in terms of mortality, stroke, and cardiovascular hospitalization. The safety endpoint is to ensure that perioperative mortality related to emergent surgical interventions does not differ between the two study groups.

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Supervisor: Prof. Matteo Bertini

Project Title: Physiology and Clinical Benefits of Conduction System Pacing

Project Description: Conduction system pacing (CSP) represents a significant innovation in cardiac pacing therapy. This observational, prospective study compares CSP (His bundle pacing [HBP] and left bundle branch area pacing [LBBAP]) with right ventricular (RV) pacing. Procedural, electrical, clinical, and advanced echocardiographic parameters will be evaluated one month after treatment.

It is expected that CSP will improve electrical parameters and ventricular function compared to RV pacing, with LBBAP showing superiority over HBP. The study aims to identify the clinical and physiological benefits of CSP.

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Supervisor: Prof. Massimo Busin

Project Title: Development of a Hybrid Bioengineered Device for Transplantation

Project Description: Despite advancements in keratoplasty, some patients, such as those with repeated failures due to immunological rejection, do not achieve satisfactory outcomes. Plastic artificial keratoprostheses offer an alternative but are associated with severe complications in 50% of cases, such as glaucoma and extrusion. This project aims to develop a hybrid device with a plastic optical component coated with decellularized corneal tissue from donors to improve integration and reduce complications. The implantation technique and biocompatibility will be tested in patients with advanced corneal pathologies, with a focus on long-term outcomes.

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Supervisor: Prof. Valeria Bertagnolo

Co-supervisor: Dr. Federica Brugnoli

Project Title: Diallyl Disulfide: A Potential Natural Approach for Breast Cancer

Project Description: Diallyl Disulfide (DADS), a natural compound derived from allicin, will be studied to establish its therapeutic potential in the HER2+ subtype of breast cancer. Using structural prediction software, possible molecular interactions between DADS and HER2 will be explored. Biochemical and molecular biology techniques will be employed to understand its mechanisms of action and the signaling pathways involved.

The study will initially utilize bi-/three-dimensional models, followed by validation in in vivo models. The ultimate goal is to contribute to identifying new approaches to enhance the effectiveness of treatments for the most aggressive breast cancer phenotypes.

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Supervisor: Prof. Veronica Tisato

Co-supervisor: Prof. Donato Gemmati

Project Title: Epigenetic "Tuning" and Stem Cells for the Development of Regenerative Medicine Strategies

Project Description: Regenerative therapies based on 3D scaffolds represent a promising area of research for complex conditions such as vascular aging. After an acute myocardial infarction (AMI), damaged cardiac tissue initiates a repair process involving the formation of a fibrin network that supports myocardial regeneration. However, in the context of advanced aging, this process is suboptimal and leads to adverse cardiovascular events (MACE), such as heart failure and wall remodeling, in many patients.

This study aims to identify a post-AMI molecular signature of epigenetic biomarkers (methylation, telomeres, miRNA) that can potentially be modulated to develop advanced personalized regeneration protocols.

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Supervisor: Prof. Katia Varani

Project Title: Efficacy, Safety, and Pharmacoeconomic Profile of Innovative Cancer Treatments with a Focus on Gender Differences

Project Description: This project aims to conduct an observational, retrospective study to monitor the efficacy and safety profile as well as the pharmacoeconomic profile of innovative drugs and potential therapeutic protocols for cancer in a real-world evidence (RWE) setting.

The primary outcome to be investigated is progression-free survival (PFS), defined as the time from the first administration to disease progression. The secondary outcome is overall survival (OS), which is the time from the first administration to patient death from any cause. PFS and OS will subsequently be analyzed across various subgroups of interest.

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Supervisor: Prof. Roberto De Giorgio
Project Title: Comparison Between Capillary and Serum Lactate Levels in Assessing Short-Term Prognosis in Septic Patients

Project Description:
Sepsis is a life-threatening condition associated with circulatory impairment, leading to elevated plasma lactate levels, a predictor of mortality. An increase in lactate levels from 2 to 4 mmol/L raises the 28-day mortality rate by 15%. A reduction in lactate levels is associated with improved outcomes.

Arterial and venous samples are accurate for lactate levels <4 mmol/L, while venous tests are more sensitive above this cut-off. Capillary lactates could detect early tissue hypoperfusion. The assessment of capillary lactates may provide early diagnosis in high-risk patients with poor prognosis.

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Supervisor: Prof. Marco Mura

Project Title: Development of an Artificial Corneal Stroma to Improve Corneal Transplant Outcomes

Project Description: Corneal transplantation is highly effective, but the global shortage of donor corneas limits access to treatment. Diseases affecting the anterior cornea with a healthy endothelium could benefit from an artificial corneal stroma. This research aims to develop a biocompatible and transparent artificial cornea that mimics human properties for treating conditions such as keratoconus and corneal dystrophies.

In collaboration with the Veneto Eye Bank Foundation (FBOV), the project involves cell sourcing, biomaterial selection, and the use of advanced biofabrication techniques such as 3D bioprinting. Transparency will be evaluated using FBOV’s standardized device, while structural analysis will employ OCT, confocal microscopy, and histological methods. Ex vivo suture testing will assess clinical suitability, promoting global access to corneal transplantation.

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Supervisor: Prof. Gianluca Campo

Project Title: Multimodal Cardiac Imaging and Ventricular Resynchronization Therapy

Project Description: The aim of the research project is to evaluate whether a multimodal imaging approach (transthoracic echocardiography and cardiac magnetic resonance imaging) provides a more accurate diagnostic option for assessing cardiac remodeling and response to cardiac resynchronization therapy.

The main echocardiographic parameters evaluated include: B-mode assessment of cardiac volumes and function; speckle tracking analysis; myocardial work. CMR parameters include: SSFP sequences for the evaluation of ventricular dimensions and kinetics; IRGE sequences with PSIR technique for quantification of Late Gadolinium Enhancement; MOLLI sequences for T1 mapping and extracellular volume (ECV) calculation.

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Supervisor: Prof. Elisabetta Caselli

Project Title: Development and Optimization of Innovative and Sustainable Systems for Infectious Risk Management in the One-Health Perspective

Project Description: This research project aims to optimize and apply innovative biological systems for infection control and prevention through the stable modulation of the environmental microbiome. This approach seeks to limit the use of chemical disinfectants that are harmful to the environment and potential inducers of antimicrobial resistance in pathogens.

These systems will be tested in healthcare and/or high-human-traffic community settings, as well as in animal farming environments (in line with the One Health perspective). The goal is to evaluate their ability to reduce infectious risk and stably modulate the environmental microbiome by eliminating pathogenic components and restoring the eubiosis of the resident microbial community.

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Supervisor: Prof. Matteo Bertini

Project Title: Correlation Between Left Atrial Thrombosis Detected by Cardiac CT and Echocardiographic Parameters of Atrial Function in Sinus Rhythm Patients with Transthyretin Cardiac Amyloidosis

Project Description: The search for predictors of left atrial thrombosis (LAT) in transthyretin cardiac amyloidosis (ATTR) represents an opportunity for risk stratification. This study will include ATTR patients in sinus rhythm, subjecting them to echocardiography, Holter ECG, and cardiac CT.

The primary endpoint will be the detection of LAT on CT, while secondary endpoints include the identification of occult atrial fibrillation (AF), the correlation between atrial strain and LAT, ischemic events, and changes in atrial function in response to TTR stabilizer therapy. The findings could confirm the relationship between atrial function, LAT, and cardioembolic events, as well as support the extension of pharmacological therapy to a broader patient population.

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Supervisor: Prof. Licia Uccelli

Project Title: Targeted Radiotherapy with CuCl2 for the Treatment of Peritoneal Carcinomatosis: Preclinical Study on the Therapeutic Efficacy of Radionuclides 64Cu and 67Cu

Project Description: The aim of the project is to develop an innovative therapeutic approach to overcome the limited efficacy and severe side effects of current pharmacological treatments for peritoneal carcinomatosis, a common metastatic complication in many cancers.

The research, conducted in vitro and in vivo, focuses on the development of radiopharmaceuticals containing radioactive copper ([64 or 67Cu]CuCl2). Once introduced into the body, these compounds are designed to cross cellular barriers and reach the nucleus, depositing their cytotoxic energy during and after their journey. This process leads to the suppression of proliferative activity and the death of tumor cells.

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Supervisor: Prof. Riccardo Gavioli

Co-supervisors: Prof. Francesco Nicoli, Dr. Elena Torreggiani

Project Title: Analysis of the Immunomodulatory and Adjuvant Profile of HIV Tat Protein and Its Peptide Derivatives

Project Description: My research focuses on analyzing the immunomodulatory properties of the HIV Tat protein and its peptide derivatives, evaluating their use as vaccine adjuvants. The study includes an in vitro phase, where the ability of the Tat protein and its peptide derivatives to enhance lymphocyte functionality during the immunological priming process is assessed, and an in vivo phase, where the adjuvant potential of these molecules is evaluated in the context of a vaccination model against SARS-CoV-2 in mice. The aim is to develop an adjuvanted vaccine that improves the quantitative and qualitative efficacy of the induced immune response, while also enhancing its durability.

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Supervisor: Prof. Matteo Bovolenta

Project Title: Development of Therapeutic Strategies to Restore Transcription of the Coagulation Factor VII Gene Affected by Promoter Mutations

Project Description: The project aims to develop transcriptional activation systems (TALE-TF and CRISPRa) to counteract the effects of promoter mutations in the coagulation Factor VII (FVII) gene, which cause a rare disorder that can lead to fatal hemorrhages (FVII Deficiency).

The objective is to produce AAV viral vectors to deliver these therapeutic systems in vivo in a murine model of FVII deficiency generated in our lab. The viral vectors will be validated in a liver cell line with a promoter mutation of the FVII gene introduced via Base Editors. The most effective systems will then be injected into FVII-deficient mice, and expression will be monitored every three weeks through plasma and liver analyses.

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Supervisor: Prof. Francesco Parmeggiani

Project Title: Development of a Formula for Calculating Intraocular Lens (IOL) Power for Cataract Surgery Combined with Endothelial Keratoplasty (EK)

Project Description: When performing endothelial keratoplasty (EK) and cataract surgery, postoperative hyperopic shift represents the main barrier to achieving uncorrected visual acuity. This prospective study will analyze refractive outcomes to develop a new formula for calculating intraocular lens (IOL) power.

The dataset will be randomly divided into a training set and a validation set. Machine learning (ML) algorithms based on nonlinear regression models will be developed using the "caret" package in the R statistical software. Computational techniques based on machine learning allow for the integration of additional variables into the predictive model, tailoring the power calculation to specific clinical conditions.

An ML-based algorithm has the potential to increase the cost-effectiveness of the combined procedure (triple EK), improve refractive outcomes, and enhance overall quality of life.

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Supervisor: Prof. Roberta Rizzo

Project Title: Achatina fulica and Haematococcus pluvialis as Natural Sources of Therapeutic Agents for Experimental Pharmacological Applications

Project Description: My PhD project focuses on studying the snail secretion of an exotic species called Achatina fulica, better known as a serious threat to the environment and public health rather than for the remarkable properties of its secretion. Thanks to a collaboration with Can Tho University in Vietnam and the spin-off SETs – Snail Extract Therapeutics, I am working on enhancing this substance as a source of bioactive compounds for pharmacological use.

Another source of bioactive compounds I am studying is the microalgae species Haematococcus pluvialis, with the aim not only of optimizing astaxanthin production processes but also of investigating the by-products derived from such production.

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Supervisor: Prof. Veronica Tisato

Co-supervisor: Prof. Donato Gemmati

Project Title: Host Genetics and Clinical Profile in COVID-19: Predictive Models Using Machine Learning

Project Description: COVID-19 has overwhelmed healthcare systems, forcing them to manage patients without tools to prioritize those at high risk. The unpredictable course of the disease has highlighted the importance of individual genetics in determining clinical phenotypes. This project aims to develop a predictive machine learning model for COVID-19 mortality, combining genetic and clinical data to identify the risk of severe outcomes early and improve patient management. Using a dataset of hospitalized Italian patients recruited during the first wave, the project will train and compare three algorithms (GBM, XGB, RF) to explore this complex pathology within a P4 medicine framework.

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Supervisor: Prof. Paola Rizzo

Project Title: Study of Molecular and Cellular Mechanisms Underlying Aortic Valve Calcific Disease and Concurrent Cardiac Amyloidosis

Project Description: Aortic valve calcification, which leads to aortic stenosis (AS), results from the dysregulation of biological processes. Currently, there are no therapeutic approaches to slow or halt its progression, with valve replacement via mechanical valve or bioprosthesis (BV) being the only available intervention. Among the partially characterized causes are inflammatory processes, somatic mosaicisms, and deregulation of the Notch pathway. In some patients, alongside valve calcification, cardiac amyloidosis (CA) is also present, with the accumulation of amyloid fibrils. The aim of this project is to characterize the molecular and cellular mechanisms underlying CAVD and clarify the causal relationship between AS and CA.

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Supervisor: Prof. Roberta Rizzo

Project Title: Highly Homologous sNS1 Proteins of Flaviviruses Influence Beta-Amyloid Deposition, Immunoregulation, Angiogenesis, and Coagulation Processes

Project Description: My PhD project focuses on studying the effects mediated by the NS1 protein derived from neurotropic and hemorrhagic Flaviviruses on inflammation in the central nervous system and coagulation pathways. Since NS1 is the only protein consistently found during Flavivirus infections and exhibits a high degree of homology across different viruses but with distinct glycosylation patterns, my research aims to evaluate its impact on various pathogenetic processes related to Flavivirus infections (WNV, YFV, TBEV, JEV, DENV). By leveraging advanced transcriptomic, proteomic, and functional approaches, this research seeks to identify novel pathways for therapeutic intervention.

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Supervisor: Prof. Massimo Busin

Project Title: Long-Term Evaluation of Repeat Endothelial Keratoplasty

Project Description: Currently, both Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) and Descemet Membrane Endothelial Keratoplasty (DMEK) are used to treat failed endothelial grafts. Since the risk of graft failure is higher in repeat procedures compared to primary keratoplasty, performing a DMEK is preferable due to its lower rate of endothelial rejection. However, in eyes that have already undergone surgery, poor visibility and the complex anatomy of the anterior chamber result in less control of the DMEK graft compared to the DSAEK graft. This study aims to compare the long-term effectiveness of DMEK and DSAEK in the re-transplantation of previously failed endothelial keratoplasties.

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Supervisor: Prof. Matteo Marti

Project Title: Evaluation of Gender Response to the Pharmacological and Toxicological Effects of New Psychoactive Substances (NPS): Preclinical In Vitro and In Vivo Studies

Project Description: The term NPS refers to synthetic and semi-synthetic substances designed to evade regulatory controls and legal consequences, mimicking the effects of traditional drugs of abuse (e.g., cannabis, cocaine, heroin). The vulnerability to abuse and the effects induced by many of these substances can significantly differ based on the subject's gender. Therefore, this project aims to study the potential sensitivity to NPS-induced effects linked to gender, correlating this difference to physiological factors (hormonal variations, pharmacodynamic, and pharmacokinetic differences) that could significantly influence the pharmacological and toxicological response.

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Supervisor: Prof. Luca Maria Neri

Co-supervisor: Dr. Mariaconcetta Sicurella

Project Title: Analysis of Molecular Mechanisms Underlying the Interaction Between Hedgehog and PI3K/Akt/mTOR Signaling Pathways in T and B Acute Lymphoblastic Leukemia Cell Models

Project Description: The Hedgehog (Hh) and PI3K/Akt pathways play a crucial role in regulating cell proliferation, survival, and tumorigenesis. This project focuses on understanding the molecular mechanisms underlying the crosstalk between the Hedgehog (Hh) and PI3K/Akt/mTOR pathways in acute lymphoblastic leukemia (ALL) by using inhibitors targeting specific components of each pathway. Through cellular biology investigations (cytotoxicity, western blotting, flow cytometry, and immunocytochemistry) and molecular studies (gene expression silencing and epigenetic analysis of miRNA expression), the project aims to identify novel therapeutic targets specific to each signaling pathway studied within these hematological malignancies.

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Supervisor: Prof. Giacomo Pietro Ismaele Caio

Project Title: Identification of a Biomarker in Patients with Non-Celiac Gluten Sensitivity: A New Diagnostic and Therapeutic Target Related to the Gut Microbiota

Project Description: Non-celiac gluten sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms that occur after the ingestion of gluten/wheat and disappear with its elimination. The pathogenesis is unclear, but alterations in the microbiota and intestinal barrier permeability appear to be crucial factors. Currently, there is no biomarker available to identify NCGS. In this study, we will compare patients with celiac disease, NCGS, and healthy controls, assessing potential differences in microbiome biodiversity before and after a gluten-free diet. The aim is to identify a specific microbial biomarker for NCGS that can be used for disease diagnosis.

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Supervisor: Prof. Riccardo Gavioli

Co-supervisors: Prof. Francesco Nicoli, Dr. Barbara Ensoli

Project Title: Evaluation of the Presence and Functionality of Anti-Tat Antibodies

Project Description: The project aims to assess the presence and functionality of anti-Tat antibodies in vaccinated HIV-positive patients. The Tat protein is crucial for viral replication and disease progression. Studies suggest that anti-Tat antibodies may reduce infection progression and improve the response to antiretroviral therapy. Antibody-dependent cellular cytotoxicity (ADCC) and immune functionality will be analyzed. ELISA assays will be used to quantify antibodies, while RFADCC assays will evaluate the destruction of infected cells. Results will be correlated with clinical parameters such as viral load and CD4+ count.

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Supervisor: Prof. Peggy Carla Raffaella Marconi

Project Title: Molecular Aspects of Herpes Simplex Virus and Cellular Pathways Involved in Viral Reactivation, Latency, and Recurrence

Project Description: Herpes simplex virus type 1 (HSV-1) is a neurotropic human pathogen that establishes a long-term interaction with its host. Following a primary epithelial infection, HSV-1 establishes a latent state in sensory ganglia, from which it can periodically reactivate, causing chronic inflammation and suggesting a potential link to neurodegenerative diseases (e.g., Alzheimer’s disease). Despite its widespread nature, the pathogenic mechanisms and immune evasion strategies of HSV-1 remain poorly understood. This study aims to investigate the role of the viral protein ICP27 in modulating various pathways, including apoptosis, inflammasome activation, cellular proteostasis (heat shock proteins), and neurodegeneration.

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Supervisor: Prof. Valeria Bertagnolo

Co-supervisor: Dr. Silvia Grassilli

Project Title: Study of the Role of Vav1 Protein in the Differentiation of Pancreatic Beta Cells

Project Description: This project aims to investigate the role of the Vav1 protein, which is involved in numerous cytoplasmic and nuclear processes, in the differentiation of induced pluripotent stem cells (hiPSCs) into insulin-producing cells. Specifically, the goal is to determine whether the modulation of Vav1 expression at specific stages of the maturation process affects the formation/functionality of β-like cells, as well as to identify its specific role in the signal transduction mechanisms leading to insulin production. The study aims to contribute to improving the efficiency of generating replacement cells for the treatment of type 1 diabetes.

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Supervisor: Prof. Roberto De Giorgio

Co-supervisor: Prof. Angelina Passaro

Project Title: New Analgesia Techniques in Patients with Blunt Chest Trauma and Multiple Rib Fractures: Use of Serratus Anterior Muscle Fascial Nerve Block in the Emergency Department

Project Description: New Strategies for Analgesia in Acute and Chronic Pathologies in the Emergency Department. This PhD project aims to demonstrate how the use of an integrated analgesia protocol—combining a pharmacological approach with fascial nerve block techniques—can safely improve pain management in the short, medium, and long term for patients with multiple rib fractures compared to traditional analgesic strategies based solely on pharmacological treatments. The study seeks to reduce complications and hospitalization time while significantly enhancing the patient experience, not only in terms of physical pain relief but also by positively impacting psychological well-being and mitigating hospital-induced trauma.

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Supervisor: Prof. Stefania Merighi

Project Title: Caffeine and Adenosine A2A Receptor Antagonism: A Novel Strategy to Reduce Cognitive Decline in Alzheimer’s Disease

Project Description: Caffeine (1,3,7-trimethylxanthine) is a natural psychoactive substance that acts as a neuromodulator, protecting the central nervous system from neurodegenerative diseases. It functions as an antagonist of adenosine receptors (A1, A2A, A2B, and A3), influencing sleep, cognition, and memory. These effects may prove beneficial in preventing and slowing neurodegenerative diseases such as Alzheimer’s disease. Given the increasing incidence of this condition, the research project aims to evaluate the neuroprotective effects of caffeine as a non-selective antagonist of the adenosine A2A receptor in in vitro cellular models of Alzheimer’s disease.

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Supervisor: Prof. Veronica Tisato

Co-supervisor: Prof. Donato Gemmati

Project Title: Synergistic Approach to Aging Based on Omics Sciences: Impact of Nutrition, Lifestyle, and Sex on Elderly Health and Cognitive Status

Project Description: Aging is a multifactorial process influenced by genetic, environmental, and behavioral factors. Distinctive molecular markers include genomic instability and epigenetic modifications, which are particularly relevant in the aging process. Recent studies associate metabolic changes, inflammation, and apoptosis with epigenetic factors. Epigenetics, situated at the intersection of the genome and the environment, offers new perspectives for health, prevention, and treatment of age-related diseases. This interdisciplinary project aims to integrate biological, epidemiological, behavioral, and environmental determinants to develop translational sex-oriented preventive, diagnostic, and therapeutic strategies in line with the principles of precision medicine.

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Supervisor: Prof. Gianluca Campo

Project Title: Correlation Between Plaque Vulnerability Assessed by OCT and Coronary Physiology Analysis in Non-Culprit Lesions of Elderly Patients With NSTEMI

Project Description: This study will include patients with acute coronary syndrome and multivessel disease. The analysis will focus on non-culprit lesions where a comprehensive coronary physiology evaluation has been performed, including FFR, FFR pullback, IMR, and CFR, along with intravascular imaging assessment via OCT. The study objectives are to evaluate whether positive FFR values correlate with unstable plaques and to determine whether indices of microvascular dysfunction or FFR pullback measurements can enhance the ability of FFR to predict the presence of vulnerable plaques.

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