Available projects
FIXED PROJECTS / fellowships
Fellowships are linked to the following projects
(listed in the order they are presented in the official call for applications)
Title and Supervisor | Description |
SB1 (senza borsa) “Clinical utility of liquid biopsy in the treatment of endometrial cancer” prof. Gustavo Baldassarre (CRO, Aviano) |
In the last years the diagnosis and treatment of Endometrial carcinoma (EC) profoundly changed with the introduction of molecular classification and immunotherapy. On molecular point of view EC are divided in four groups on the presence/absence of alterations in POLE and TP53 genes and the presence of Microsatellite Instability (MSI). MSI EC are extremely sensitive to immunotherapy, while TP53 mutated ones are not. Based on disease stage and on molecular classification, EC patients are treated with Chemo + Radio or Chemo + Immuno-therapies. |
SB2 (senza borsa) “Development of Diagnostic Tools for cancer via the use of NGS” prof. Claudio Tiribelli (FIF, UniTS) |
The primary objective of this project is to develop advanced diagnostic tools for cancer detection and analysis using Next-Generation Sequencing (NGS) technology. This involves creating more precise, efficient, and comprehensive diagnostic methods to identify genetic mutations biomarkers associated with various types of cancer (Lymphomas and Myelomas), thereby improving early detection, personalized treatment, and patient outcomes. |
C1 “Epigenetic regulation of the response to therapies in ovarian cancers” prof. Gustavo Baldassarre (CRO, Aviano) |
Epithelial Ovarian cancer (EOC) is still a deadly disease mainly for the appearance of recurrences resistant to first lines therapies. Gold standard treatment for EOC patients include radical surgery followed by platinum-based therapy. Introduction of maintenance treatment with PARP inhibitors, strongly improved the survival of platinum sensitive EOC. Nevertheless platinum-resistant EOC are usually cross resistant with PARP inhibitors and largely uncurable. |
C2 “Exploring the biological diversity of luminal breast cancer with patient derived models” prof. Gustavo Baldassarre (CRO, Aviano)
|
Breast cancer is the most common cancer in women with more 55.000 cases each year only in Italy. Yet, it is not a single disease but different histotypes and molecular subtypes exist. This project aims understanding the biological diversity of Luminal Breast Cancer (LBC), the most common molecular BC subtypes. LBC might have a very favorable course or become readily resistant to treatment with hormonal therapies. LBC have a peak of recurrences two years after the original surgery but could also recur many years later. LBC could appear as indolent tumor localized to the breast but also as highly aggressive metastatic disease. |
D3 “Interaction between SARS-CoV-2 and cellular pathways” dr. Giuditta De Lorenzo (AREA, Trieste) and prof. Marco Scocchi (DSV, UniTS) |
Severe COVID-19 is characterized by the inefficient suppression of early stages of infection followed by an exacerbated response once the virus has proliferated, resulting in hyperinflammation and cytokine storm, acute respiratory syndrome, tissue damage, multi-organ failure, with long-term effects known as Long COVID. |
D4 “A synaptic mechanogenetic stimulation as treatment for early infantile epileptic encephalopathy type 9” prof. Maria Passafaro (Institute of Neuroscience, Milano) |
Mutations in the X-chromosome gene PCDH19 cause DEE9. DEE9 is characterized by early-onset epilepsy and very heterogeneous spectrum of neuropsychiatric symptoms, including intellectual disability. |
MD5 “In vivo cellular fate-mapping studies to investigate the contribution of candidate genes involved in lung regeneration and pulmonary fibrosis” prof. Marco Confalonieri (DSM, UniTS) |
This research project aims to assess the therapeutic relevance of selected targets in curing Idiopathic Pulmonary Fibrosis, focusing specifically on the effects of these targets on alveolar epithelial type II (ATII) cells. The project will utilize both in vitro techniques, using primary mouse ATII cells, and in vivo techniques with transgenic (Tg) mouse models that allow ATII-restricted gene manipulation and lineage tracing. The efficacy of the selected therapeutic targets will be examined at cellular and molecular levels both in vitro and in vivo. First, the selected targets will be functionally assessed for their ability in restoring ATII to ATI trans-differentiation in diseased ATII cells through gene manipulation in vitro. Second, to gain a deeper understanding about their role in combating IPF phenotype in vivo, the relevance of the selected targets will be further assessed in vivo by leveraging a mouse model of ATII-restricted expression of CRISPR-associated protein 9 (CAS9) endonuclease challenged either by bleomycin administration or pneumonectomy (PNX). This model will enable the ATII-restricted knockout of selected molecular targets and consequently assess the impact on both lung repair and compensatory lung growth. This research will lead to the identification and validation of new druggable targets for the treatment of Idiopathic Pulmonary Fibrosis. |
MD6 “Development of precise gene editing strategies to cure inherited cardiomyopathies” prof. Mauro Giacca (DSM, UniTS) |
The project aims to develop effective protocols for the precise correction of the DNA mutations that cause genetically inherited cardiomyopathies. These are relatively frequent cardiac disease conditions, with a prevalence of 1:500 individuals in the general population for hypertrophic cardiomyopathy (HCM). The PhD student will develop lipid nanoparticles that specifically target cardiomyocytes and methods that induce homology directed repair using an exogenously administered normal DNA sequence, used as a template for genetic correction. The developed methods will be tested in parallel in human iPS cell-derived cardiomyocytes from patients with myosin binding protein C (MYBPC3) mutations (the most frequently affected gene in HCM) and in a mouse model with a humanised mutation in the same gene. |
MD7 “Impact of the tissue microenvironment on oncogenic signaling during tumor initiation and evolution” prof. Giannino Del Sal (ICGEB, UniTS) |
Research activity of the Cancer Cell Signaling group aims at understanding the interplay between tissue microenvironment and oncogenic signaling in cancer, with the ultimate goal to develop preventive and therapeutic strategies. |
MD8 “Prolyl isomerase PIN1 inhibition as a strategy against aggressive tumours” prof. Giannino Del Sal (ICGEB, UniTS) |
|
MD9 “Novel strategies to fight multi-resistant bacterial pathogens” prof. Paola Cescutti (DSV, UniTS) |
Multi-drug resistance (MDR) in bacteria have reached worrisome levels. Treatment of MDR bacterial infections is very often unsuccessful, because of the lack of efficacious antibiotics and has become a major public health problem. The most dangerous MDR bacteria belong to the ESKAPE group which includes Klebsiella pneumoniae. This situation is so alarming that CDC and WHO indicated some of these species as “urgent threats” or “critical priority” pathogens. |
MD10 “Role of the chromatin architectural factor HMGA1 in modulating the secretome of breast cancer cells” prof. Guidalberto Manfioletti (DSV, UniTS) |
Triple-negative breast cancer (TNBC) is a heterogeneous subtype of tumor. Patients with TNBC have a relatively poorer outcome compared to those affected by other BC subtypes, because of the typically aggressive cancer behavior and the absence of recognized targets for specific therapies. |
MD11 “Dissecting the oxinflammatory mechanisms involved in Rett Syndrome pre-symptomatic/ symptomatic switch: focus on mitochondria and inflammasome activation” prof. Gabriele Baj (DSV, UniTS) |
Rett syndrome (RTT) is a genetic neurodevelopmental disorder characterized by progressive regression of mental and psychomotor development (symptomatic phase).Evidence indicates that metabolic abnormalities including mitochondrial dysfunction, aberrant redox homeostasis and subclinical inflammation significantly contribute to RTT. While many abnormal molecular and cellular aspects of RTT have been fairly delineated in its symptomatic phase, what happens before the onset of symptoms still remains unknown. However, the peculiar pathogenic development of RTT characterized by a relatively slow transition to the symptomatic stage offers a precious time window of opportunity for early diagnosis and intervention. Based on these premises, we intend to identify the chain of molecular events involved in the enigmatic switch from presymptomatic to symptomatic stage of RTT. We plan to take advantage of suitable in vivo, in vitro and ex vivo models of RTT, such as Mecp2-null mouse model, RTT patient iPSCs and serum samples.We will evaluate KO mice primary cells and human iPSCs from RTT patients monitoring overtime the mitochondrial/inflammasome hallmarks related to the presymptomatic/symptomatic switch. The accomplishment of this project would help to furthering the understanding of RTT pathophysiology. |
MD12 “Dissection of cancer stemness and therapy resistance by functional genomics” prof. Stefan Schoeftner (DSV, UniTS) |
Epithelial ovarian cancer (EOC) is the most lethal gynaecological cancer with > 60.000 new cases per year in the US and EU and single therapy that is beneficial for all EOC patients is currently not available. Preliminary data show that the self-renewal transcription factor OCT4 enhance EOC aggressiveness by programming a tumor promoting microenvironment. In this context OCT4 is tightly regulated by a derivative pseudogene lncRNA that deposits epigenetic silencing complexes to the OCT4 promoter using an unprecedented epigenetic mechanism, thus impinging on ovarian cancer aggressiveness and patient survival. This highlights the relevance of a tight regulation of OCT4 dependent cancer pathways to define the tumor microenvironment (TME) in EOC. |
MD13 “Investigating HPCAL4 as a Therapeutic Target for Episodic Ataxia Type 2 and Epileptic Encephalopathy 42” prof. Lorenzo Cingolani (DSV, UniTS) |
The project explores the potential of the unknown ‘Tdark’ gene HPCAL4 for developing gene therapies for ataxia and epileptic encephalopathy. The focus is on deciphering how HPCAL4 regulates CACNA1A, a pivotal calcium channel implicated in various brain disorders. Through cutting-edge techniques (super-resolution imaging, electrophysiology and optogenetics), you will delve into the intricate workings of nerve cell communication. |
C14 “ICGEB position”
|
One (1) position available to work in one of the research groups at ICGEB. |
FSE+15 “UniTS position" |
This fellowship can be linked to any one of the flexible projects described at the bottom of this table (see below)
|
FSE+16 “Development of precision oncology approaches for women cancers" prof. Barabra Belletti (CRO, Aviano) |
The project aims to identify new therapeutic targets for the treatment of patients with advanced/metastatic breast or gynecological cancers. It involves a first phase of genomic analyzes on samples collected at the Aviano IRCCS CRO, using innovative NGS technologies to highlight alterations associated with progression. Subsequently, the identified alterations will be targeted using both genetic and pharmacological approaches, also in patient-derived models (PDO and PDX). |
RB1 “ICGEB position” |
One (1) position reserved for candidates graduated from foreign universities to work in one of the research groups at ICGEB. |
RC1-2 "FIF positions" |
Two (2) positions reserved for citizens of the Philippines recipient of a fellowship funded by the Philippine Council for Health Research and Development (PCHRD) to conduct research at the Italian Liver Foundation (FIF).
|
FLEXIBLE PROJECTS
Fellowship FSE+15 can be linked to any one of the following projects
(listed in alphabetical order by supervisor's name)
Title and Supervisor | Description |
"Investigation of endothelial cells for the improvement of ovarian tissue autotransplantation technology" prof. Roberta Bulla (DSV, UniTS) |
Premature ovarian failure is associated with childhood cancer treatment. Ovarian tissue cryopreservation followed by transplantation is the only available option for prepubertal girls who have survived cancer. Revascularization is one of the limiting factors for successful ovarian tissue transplantation. The aim of this project is to develop a tissue-engineered product (TEP) to improve the success rate of autologous ovarian transplantation, reduce the ischemic window and improve recovery and survival. To this end, the following objectives are proposed 1. Inosculation selected matrices, possibly commercial matrices used clinically for wound healing, with autologous endothelial cells isolated from human skin or alternatively with the stromal vascularized fraction (SVF), a heterogeneous collection of cells contained in adipose tissue 2.Evaluate the ability of this vascularized TEP to improve implantation and survival of ovarian tissue sections before and after cryopreservation 3. investigate the innate immune response to ovarian tissue damage to determine markers of ovarian ischemia that may be useful for understanding the mechanisms leading to ovarian ischemia after cryopreservation. |
"Understanding astroglia contribution to seizure propensity in Rett syndrome " prof. Francesca Cesca (DSV, UniTS) |
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl-CpG Binding Protein 2 (MeCP2) gene. About 60% of RTT patients show epileptic seizures, however, epileptogenesis in RTT is still poorly understood. We are interested in understanding the contribution of astrocytes to seizure propensity in RTT. |
"Mechanisms of inactivation of the tumor suppressor DAB2IP in cancer" prof. Licio Collavin (DSV, UniTS) |
The RasGAP protein DAB2IP negatively modulates multiple oncogenic pathways, such as Ras/RTK, TNF/NF-kB, PI3K/AKT, and WNT/beta-catenin, thus acting as a bona fide tumor suppressor. DAB2IP expression is often reduced by gene methylation in tumors. However, in many cancers the gene is not silenced, and its functions is inhibited by other mechanisms (Bellazzo, 2016). For instance, we discovered that DAB2IP can be disabled by interaction with mutant forms of the p53 protein, with crucial implications for cancer aggressiveness in response to inflammation and to Insulin (Di Minin, 2014; Valentino, 2017). We also found that DAB2IP protein levels can be reduced both in cancer cells and in non-cancer cells of the tumor stroma, suggesting the existence of a cell non-autonomous mechanism of DAB2IP inactivation, that may be very important for cancer progression. This project has two main objectives: 1) to further characterize the mechanisms of DAB2IP inactivation in cancer, study their functional impact, and evaluate their diagnostic and prognostic potential; 2) to explore approaches aimed to restore DAB2IP functions in cancer cells as innovative cancer therapeutics. |
"HCC therapeutics" prof. Gabriele Grassi (DSM, UniTS) |
Hepatocellular carcinoma (HCC), an important cause of global death, develops in 90% of cases in the context of hepatic fibrosis (HF). HCC and HF represent a significant burden on healthcare in terms of costs and personnel commitment. |
"Identification of cancer-derived factors modulating the tumor ecosystem." prof. Fiamma Mantovani (DSV, UniTS) |
Tumors behave as complex and dynamic ecosystems where cancer cells interact with cellular and non-cellular stromal and immune components. Alterations of the tumor microenvironment (TME) affect cancer cells’ fate, metastatic capability and therapy response, yet the mechanisms and cell types at play remain understudied. Our lab identifies proteins and non-coding RNAs acting either in a cell-autonomous or in a paracrine fashion to reshape primary and metastatic tumor niches, generating permissive environments supporting tumor growth, immune evasion, metastatic colonization and therapy resistance. These factors may represent biomarkers and/or actionable targets for improving treatment of aggressive tumors. We focus on candidate factors (proteins and miRNAs) produced by aggressive tumor cells downstream of oncogenic pathways in response to cancer-related stimuli (including hypoxia, mechanostimulation and inflammatory cues), that impinge on the communication between tumor, stromal and immune-inflammatory cells. The PhD candidate will evaluate the functional relevance and the mechanism of action of selected factors by analyzing the impact of their genetic/pharmacologic modulation on tumor-TME crosstalk using in vivo, ex-vivo and in vitro experimental models of breast cancer and other tumors and metastasis. Moreover, validated factors may be tested for their potential as circulating biomarkers of metastatic disease and predictors of response to treatments. |
"Exploiting novel dissipative extracellular matrix mimics to develop fundamental knowledge in CARTIlage REGENeration - CARTIREGEN" prof. Pasquale Sacco (DSV, UniTS) |
Cutting-edge biomaterials that mimic the microenvironment of natural articular cartilage (AC) are urgently needed to provide fundamental insights into AC regeneration. Indeed, AC-associated disorders still remain one of the leading causes of disability and represent a tremendous socioeconomic burden worldwide. Current biomaterials used to mimic the AC microenvironment to understand cell biology suffer from their purely elastic nature. Yet, AC represents a physiological damper of mechanical stresses. Although it has recently emerged as a novel regulator of cellular responses, the contribution of material dissipation to guiding cell-fate decisions is still in its infancy. Therefore, in the first instance the project aims to fabricate AC-inspired extracellular matrix mimics in the form of hydrogels showing tunable dissipation rate. To achieve this milestone, the PhD student will leverage recent discoveries in the Supervisor’s Lab. The second theme of the project aims to test the chondroinductive properties of the AC mimics. Chondrocytes biology as well as mesenchymal stem cells differentiation will be investigated in vitro using both 2D and 3D settings. In addition to achieving these major objectives, CARTIREGEN will also generate different intermediate goals, providing basic knowledge and pivotal elements of novelty to move forward AC tissue engineering field beyond the current state-of-the-art. |
"Combating resistant intracellular infections by Acinetobcter baumanii" prof. Marco Scocchi (DSV, UniTS) |
Acinetobacter baumannii is an opportunistic pathogen listed by theWHO in the ESKAPE group causing serious concern for their high level of antibiotic resistance. It has been recently shown that to survive and multiply eukaryotic phagocytic cells, further complicating antibiotic treatment efforts. |
"Studies on the functions and modes of action of primate cathelicidins as leads for the design of multifunctional antiinfective agents." prof. Alessandro Tossi (DSV, UniTS) |
Antimicrobial peptides (AMPs) are a first line of defence against infections and an important component of innate immunity. Among AMPs, the cathelicidin family has been extensively studied for its pleotropic effects in immunity, in both physiological and pathological environments. |
|
|
! NEW ! PNRR PROJECTS
! NEW ! |
|
"Molecular basis of synaptic plasticity determined by calcium channels in primary neurons" prof. Eugenio Fornasiero (DSV, UniTS) and Prof. Lorenzo Cingolani (DSV, UniTS) with CyNexo S.r.l. |
This project aims to investigate some of the fundamental plastic properties of neurons, the cells responsible for neurotransmitter release in the brain which are at the basis of complex behavioral functions such as memory and cognition. Specifically, the student will learn a range of advanced neurophysiological technologies and use them to elucidate the relationship between the precise subcellular localization of calcium channels at presynaptic sites and how they can be recruited by synaptic activity. The work will be developed in collaboration between UniTS, the University Medical Center Göttingen (Germany), which will be involved in advanced microscopy experiments, and CyNexo, a company excelling in mechatronic engineering, which will help develop a compact device for stimulating and reading neuronal activity. The main goals of this work are: 1) define the distribution of channels in different activity regimes using tailored and precise labeling and high-resolution microscopy; 2) clarify the impact of recruited channels on synaptic efficiency using calcium imaging and optogenetics; and 3) evaluate the role of re-localization in human pathology by studying mutant channels from patients with disorders associated with brain diseases. Overall, the project is expected to provide a new paradigm for understanding how presynaptic plasticity is regulated. |
"New non-invasive molecular biomarkers for the early diagnosis of pleural mesothelioma" Prof. Federica Tramer (DSV, UniTS) with AB ANALITICA S.r.l. |
Malignant mesothelioma (MM) is a difficult tumor to diagnose and several serum biomarkers have been investigated for the non-invasive early detection of MM, but none has achieved a sufficient combination of sensitivity and specificity. |