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.
Evaluation of DNA alterations in cfDNA could be a reliable strategy to follow EC patients during therapies and possibly help the clinicians in decision making.
The successful candidate will work in close contact with the Unit of Medical oncology to follow the clinical evolution of EC patients enrolled at CRO-Aviano. She/He will be required to learn and apply NGS-based sequences techniques to evaluate the presence of mutation and their modifications over the time, both in solid and liquid biopsies. The molecular analyses will be then related to the patients’ response to therapies to define if liquid biopsy at diagnosis and during the course of treatment could directly impact on clinical decisions and patients’ outcome.

SB2 (senza borsa)

“Development of Diagnostic Tools for cancer via the use of NGS”

prof. Claudio Tiribelli (FIF, UniTS)

C1

“Epigenetic regulation of the response to therapies in ovarian cancers”

prof. Gustavo Baldassarre (CRO, Aviano)

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.
The successful candidate will learn and apply all the molecular and cellular biology techniques used in cancer research along with in vivo analyses, working in a stimulating multidisciplinary environment and will mainly use characterized patient-derived organoids (PDO) and xenografts (PDX) to understand which are the main differences in LBC at different stages of disease. Particular focus should be applied to study the emergence of resistance to targeted therapies used as standard treatment for LBC patients. 

D3

“TBD”

dr. Giuditta De Lorenzo (AREA, Trieste) and prof. Marco Scocchi (DSV, UniTS)

D4

“A synaptic mechanogenetic stimulation as treatment for early infantile epileptic encephalopathy type 9”

prof. Maria Passafaro (Institute of Neuroscience, Milano)
and prof. Lorenzo Cingolani (DSV, UniTS)

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.
PCDH19 encodes protocadherin-19 (PCDH19), an adhesion molecule of the cadherin superfamily. The adhesive properties and synaptic expression  of PCDH19 make this protein well equipped for neuronal circuit organization, as suggested by its involvement in neuronal migration, sorting and clusterin. Furthermore, PCDH19 mismatch at synapses has recently been shown to affect NCAD-dependent signaling at presynaptic terminals of mossy fibers, impairing their function. In this project will use the synaptic methanogenetic stimulation to repair the functional impairment in DEE9. This will be studied in neuronal cultures by using magneto-mechanical stimulation in combination with imaging, biochemistry and multi electrode arrays (MEA) techniques. 

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

“TBD”

prof. Mauro Giacca (DSM, UniTS)

MD7

“TBD”

prof. Giannino Del Sal (ICGEB, UniTS)

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.
This project aims at using phage-derived compounds to combat human infections caused by MDR Klebsiella pneumoniae. The idea is to exploit the specificity of bacteriophage endoglycosidases, hydrolases that have the pathogen capsular polysaccharide as a substrate, to guide drug-carriers to the target microorganism selectively, without interfering with the host microbiome. The endoglycosidase will be anchored on the outer surface of a liposome which will carry inside a bactericidal compound. The endoglycosidase, by degrading the capsule, will allow the liposome to reach and fuse with the outer membrane of the bacterium, pouring its antibacterial content into the periplasm. As bactericidal compounds available antibiotics, like vancomycin, and spanin or disruptin of phage origin will be tested. This project is intended to be a proof of principle that such an approach can be used as an innovative and effective tool against MDR bacteria.

MD10

“Role of the chromatin architectural factor HMGA1 in modulating the secretome of breast cancer cells”

prof. Guidalberto Manfioletti (DSV, UniTS)

MD11

“Dissecting the oxinflammatory mechanisms involved in Rett Syndrome pre-symptomatic/ symptomatic switch: focus on mitochondria and inflammasome activation”

prof. Gabriele Baj (DSV, UniTS)

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.
In the current project we will  investigate how OCT4 dependent gene expression signatures and the epigenomic landscape program a tumor-promoting TME. In addition the mechanism by which the human OCT4 pseudogene 3 lncRNA (hOCT4P3) targets silencing complexes to the OCT4 promotor and alternative target genes across that epithelial ovarian cancer genome will be investigated.
The project is based on a functional genomics approach including transcritomics and epigenomics, and the application of a wide range of  bioinformatics analyses. 

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.
Previous experience in electrophysiology is desirable. The ability to thrive in an international and competitive research environment is essential.
Join a dynamic research team driven by passion and curiosity for science. Benefit from access to state-of-the-art facilities and collaboration opportunities across Europe with renowned experts in the field. With a commitment to fostering diversity and inclusion, we welcome applicants from all backgrounds.
The position is funded by the Cariplo-Telethon alliance, supporting research on Tdark genes (genes with unknown functions in rare diseases). Our laboratory adopts an integrative approach, combining molecular, imaging and electrophysiological techniques in in vitro and in vivo models of neurological disorders
(Thalhammer et al., 2017 Cell Rep 20, 333-343; Ferrante et al., 2021 Cell Rep 35 109248, Jaudon et al., 2022 Mol Ther Nucleic Acids 29 462-480, Moretto et al. 2023 Elife 12, Jaudon and Cingolani, 2024 Trends Cell Biol.).

C14

“ICGEB position”

One (1) position available to work in one of the research groups at ICGEB.
For more infromation, please visit the Scientific Faculty Research pages at the following link:

https://www.icgeb.org/the-faculty/

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)

RB1

“ICGEB position”

One (1) position reserved for candidates graduated from foreign universities to work in one of the research groups at ICGEB.
For more infromation, please visit the Scientific Faculty Research pages at the following link:

https://www.icgeb.org/the-faculty/

"Investigation of endothelial cells for the improvement of ovarian tissue autotransplantation technology"

prof. Roberta Bulla (DSV, UniTS)

"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.
This is a collaborative project between Prof. Cesca’s group at UniTS and Dr. Falcone’s group at SISSA. We will use in vitro co-cultures of human astroglia, derived from RTT patients and healthy controls, and primary rodent neurons to study how RTT astroglia induce hyperexcitability, through live Ca2+ imaging and multi-electrode array experiments. We will also perform xenotransplants of human astroglia precursors in the brain of immunodepressed mice, to study the impact of RTT astroglia on cognition, through behavioral tests, and on seizure propensity, by injecting the convulsant drug pentylenetetrazol. Focusing on human astrocytes is crucial to set the stage for translational studies.

"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.
We propose a novel therapeutic strategy based on the inhibition of the pro-HCC effects of the precancerous HF liver. The molecules used will be deubiquitinase inhibitors (2C and derivatives) developed by us. The drugs will be tested in human hepatic stellate (HSC) cell lines/primary HSCs, the major drivers of HF (collaboration with Prof Weiskirchen (Universitätsklinikum Aachen, Germany) evaluating the phenotypic/molecular effects (focus on E2F1). Since the viscoelasticity of the culture surface influences the phenotype of HSCs, we will also generate culture surfaces that mimic the viscoelasticity of the pathological liver (collaboration with Prof M Grassi, UNITS), to generate data more predictive for in vivo tests. Cellular models of steatosis/liver inflammation (collaboration with Prof Pastorin, National University of Singapore), organoids (collaboration with Prof Rizzolio, CRO, Aviano) and in vivo tests (Prof Nhung Truong, University of Science, Ho Chi Minh City) will be also undertaken to study drugs effects/mechanisms of action. The candidate will therefore have the possibility of being hosted in the collaborating centers.

"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.