Progetti di Dottorato e Finanziamenti Europei

PhD Student: Erika Di Domenico

Supervisor: Emilie Venereau

Abstract
HMGB1 is a nuclear protein released by cells upon stress or damage to act as a mediator of sterile inflammation and regeneration. A lower expression of HMGB1 within the cell, and its extracellular release have both been associated with hallmarks of aging. Our working hypothesis is that cells tend to release HMGB1 upon aging, due to constant cell stress and damage, leading to cell-intrinsic damage, as well as inappropriate inflammatory signalling and damage of cells/tissues. We will combine loss-of-function and gain-of-function experiments to decipher the contribution of HMGB1 in the aging process.

Objectives
We expect to decipher HMGB1’s contribution to the aging process, evaluating its value as biomarker to distinguish between healthy and pathological aging, and assessing the therapeutic potential of HMGB1 recombinant protein in aged cells.

PhD Student: Manuel Alejandro Montano Castillo

Supervisor: Marco Bacigaluppi

Abstract

Ischemic stroke has a worse clinical outcome in the elderly compared to young individuals. Age-related changes in the immune system may give rise to modified immune responses that could potentially impact the outcomes of strokes. We will investigate the age-related molecular and cellular changes of immune cells in elderly mice and their role in worsening ischemic stroke and identify new therapeutic targets.

Objectives

Identify molecular and cellular changes in the immune compartment that correlate with the outcome post-stroke to discover new therapeutic targets optimizing acute stroke treatment in the elderly.

PhD Student: Luisa Ricci

Supervisor: Simone Cardaci

Abstract

Cancer is considered an age-related disease. Interestingly, a hallmark of aging such as metabolic rewiring, is also instrumental in promoting malignant transformation. This project aims at understanding the molecular mechanisms driving metabolic reprogramming in cancer and determining how the metabolic landscape of the tumour microenvironment affects tumor progression.

Objectives

Using analytical chemistry, cell biology and computational approaches, we plan to identify immunometabolic features affecting tumor growth, as well as tumor-specific metabolic liabilities exploitable for clinical benefit

PhD Student: Ainhoa Viana Alzola

Supervisor: Dr. Jean-Michel Cioni

Abstract

Endosomes play essential roles in cellular function and survival by regulating multiple intracellular trafficking routes. Defects in endosomal trafficking have been shown to occur during healthy aging as well as a wide range of age-related human diseases, mainly affecting the nervous system. Proper endosomal trafficking is essential for neuronal function and survival. However, what causes the age-related impairments in endosomal functions in neurons, and the functional consequences, are not understood

Objectives

This project aims at investigating the link between impairments in endosomal trafficking and altered proteostasis in the aging brain by focusing on the molecular changes occurring on the organelle.

PhD Student: Roberta Vacca

Supervisor: Raffaella Di Micco

Abstract

Hematopoietic Stem and Progenitor Cell (HSPC) gene therapies require an ex vivo activation step which, by mostly unexplored mechanisms, can strongly reduce HSPC fitness. It is emerging that an accelerated proliferation of HSCs, which is expected to occur during manipulation in culture but also upon transplantation, might lead to DNA damage through accumulation of oxidative stress, all factors implicated in HSC aging. Therefore, we propose to integrate knowledge of aged HSC biology to preserve HSC functionality during ex vivo culture and upon transplantation.

Objectives

The project aims at identifying the molecular and cellular mechanisms of physiological aging in HSCs and apply these findings to improve the efficacy of cell and gene therapy applications for the treatment of human diseases.

PhD Student: Alessandra Weber

Supervisor: Luigi Naldini

Abstract

Editing by homology direct repair (HDR) in human HSPCs remains poorly efficient and this limits its therapeutic applications in most diseases. Novel strategies enabling enrichment of HDR-edited HSPCs would decrease competition by unedited cells, improving therapeutic efficacy and at the same time increasing safety by purging out cells harboring undesired loss of-function editing outcomes at the target site.

The aim of this PhD project is to develop innovative strategies for ex-vivo and in-vivo enrichment of human edited HSPCs harboring targeted integration of highly expressed cassettes into genomic safe harbors (GSHs).

Objectives

Selection strategies can be achieved by i) ex-vivo sorting of engineered cells by means of editing-coupled selector, or ii) conferring in-vivo selective disadvantage to cells not undergoing HDR.

PhD Student: Francesca Rita Ogliari

Supervisor: Prof. Michele Reni

Abstract

Immunotherapy (IO) alone or in combination with chemotherapy (IO-CT) has become the standard of care for most patients with metastatic Non-Small Cell Lung Cancer (NSCLC). Nevertheless, 20 to 30% of patients do not benefit from these treatments facing a negative risk-benefit balance. An artificial intelligence (AI) platform, that can automatically extract patients’ data (clinical, pathological, radiological, laboratoristic) and analyse them, would help clinicians understand and highlight interconnected patterns and predictive algoritms of cancer-specific outcomes. Our study aims to train the AI tool in-clinic and validate it on a larger multicentric scale.

Objectives

Primary objective is precocely identify patients not responding to standard IO-based treatments; secondary objectives are severe toxicity and long-survivals prediction. Co-secondary endpoint is the feasibility of such approach (AI and its integration in data sources) in clinical research.

PhD Student: Nicolo Pecco

Supervisor: Andrea Falini

Abstract

Gliomas are a heterogeneous group of brain neoplasms and the search for biomarkers to characterize molecular status or predict prognosis could be a breakthrough advancement in neuro-oncology. This project aims at identifying reliable Magnetic Resonance Imaging (MRI) biomarkers for personalized profiling of brain gliomas. An Artificial Intelligence (AI) model based on Deep Learning (DL) using transfer learning will be developed for glioma identification on retrospective conventional and advanced MRI datasets, followed by a radiomic analysis to extract relevant quantitative features linked to pathological, molecular and other clinical outcomes. DL models will be tested on a prospective cohort of glioma patients and on open-source databases (e.g., TCIA/TGCA-GBM), for external validation purposes.

PhD student : Chiara Borgonovo

Supervisor: Francesca Pola

Abstract

The research project adopts an interdisciplinary approach, integrating modern image theories and art history, to examine the material aspects of digital media in relation to artworks that incorporate technological components. It analyzes the complex challenges posed by such works at the interpretive, conservation, and curatorial levels, while tracing the historical development of media art in Italy, identifying relevant case studies, and evaluating the historical-critical, conservation, and curatorial strategies applied or applicable in such contexts.

Objectives

The main goal of the project is to identify new methodological approaches and collaborative strategies applied nationally and internationally for studying, preserving and curating media art. The project aims to generate insights that will promote knowledge advancement and help establish best practices in media art research, conservation, and curatorship within Italy.

PhD Student: Martina Giovine

Supervisore: Bianca Cepollaro

Abstract

This project concerns non-discriminatory language and its implementability within public administrations, taking on challenges such as defying inclusive language, providing a survey of the main existing proposals, trying to develop a model for assessing and evaluating them, surveying and interpreting the existing empirical studies on the topic, investigating the relationship between communication, stereotypes, and biases, assessing the existing policies and good practices.

Objectives

The aim of the project is to make an original contribution to the scientific debate and to participate in the governance, organisation and strategic direction of public administrations.

PhD Student: Edoardo La Ragione

Supervisore: Andrea Tagliapietra

Abstract

The project intends to investigate the paradigm shifts that have occurred following the entry of the "digital space" into governance practices and the forms of life it has opened up. In particular, it is necessary to think about how the space of the 'political' is being redefined today where certain traditional criteria of definition seem to no longer hold sway.

Objectives

We are expected to be able to adequately 'map' the present, reconstructing its past genealogically and trying to see possible future outcomes.

PhD Student: Giulio Pennacchioni

Supervisore: Francesca Pongiglione

Abstract

The latest IPCC reports confirm the anthropogenic origin of climate change, while adequate political actions are still lacking. Despite the consensus among moral philosophers about the importance of individual action, participation in climate mitigation is still limited. The same holds true for the collective action of institutions, whose responsibility also extends to communication and education about climate change.

Objectives:

The objective is to define the moral and epistemic responsibilities of individuals and institutions and to promote broader engagement against climate change.

PhD student: Francesca Berra

Supervisor: Andrea Galbiati

Abstract

Insomnia is characterized by difficulty initiating or maintaining sleep and resulting in daytime impairment. The hyperarousal model suggests that it is perpetuated by physiological and cognitive arousal that is influenced by stress. So sleep reactivity (SR), the degree to which stress disrupts the sleep system, is a critical concept in understanding insomnia. When SR exceeds a certain threshold, it can lead to sleep disorders. The AIE model highlights attention's role in insomnia, and understanding attentional shifting strategies could aid in managing SR. 

Objectives

Investigate the relationship between insomnia and sleep reactivity manipulating it to  evaluate the impact on subjects with and without insomnia symptoms, with a focus on REM sleep, and exploring the role of attention. 

Dottorando: Alessandra Castelnuovo

Supervisore: Maria Salsone

Abstract

Obstructive Sleep Apnea Syndrome (OSAS) is a sleep related breathing disorder, characterized by recurrent episodes of complete or partial obstruction of the upper airway leading to sleep fragmentation. OSAS has a high epidemiological impact (9-38% of general population), it is frequently reported in male and increasing with the age. Interestingly, there is evidence for a strict correlation between OSAS and neurodegenerative disorders, such as Alzheimer’s Dementia. CPAP treatment could revert OSAS related-cognitive impairment.

Objectives

The aim of this project is to create a web-based platform, to collect the clinical-instrumental data in order to identify OSAS profiles at high risk for neurodegeneration and predict the efficacy to CPAP treatment.