PNRR Projects
PNRR 2022
20 scientific research projects coordinated by the IRCCS San Raffaele Hospital have won ministerial funding from the first PNRR (National Recovery and Resilience Plan), with the objective of boosting biomedical research.
Cardiology-Pneumology
1. A new portable device for pre-hospital non-invasive ventilatory support in acute respiratory failure (PREVENT)
PI: Giovanni Guglielmo Landoni
Aim: This project aims to develop a fully functional prototype of a new portable Continuous Positive Airway Pressure (CPAP) device intended to provide respiratory support in the event of an out-of-hospital acute respiratory failure (ARF). The main features of the new device include its financial sustainability, ease of use, and safety all of which will help promote its widespread diffusion. First, the prototype will be validated in an experimental pre-clinical platform and will then undergo feasibility, efficacy, and safety testing in humans. The availability of a portable, low-cost and easy-to-use CPAP device will fill the technological gap of a medical device able to provide life-saving therapeutic intervention for ARF outside the hospital setting.
2. Prospective multicenter registry in patients with acutely decompensated heart failure admitted to cardiac rehabilitation (PROMETEO)
Substudy: the ENEA (Exercise and heart transplant) registry-based randomized controlled trial with rehabilomic assessment
Aim: The project includes two main studies: 1. a prospective multicenter Cardiac Rehabilition (CR) registry aimed at providing continuous information on CR performance; 2. a CR based RRCT , that compares different rehabilitative approaches in patients who underwent heart transplantation.
3. Macklin effect, quantitative imaging analysis and cytokine profiling to predict Lung frailty in ARDS (MACKLIN ARDS)
PI: Michele De Bonis
Aim: This project aims to identify new combined biochemical and radiological/radiomic markers that can non-invasively characterize lung frailty, specifically the predisposition to barotrauma in patients with acute respiratory distress syndrome (ARDS). The ultimate goal is to improve the current diagnostic and therapeutic standards for this condition. To achieve this the team will collect and analyze clinical data as well as specific radiological signs, such as the Macklin effect, and utilize artificial intelligence techniques to identify new lung frailty markers in a large cohort of ARDS patients, including those with and without COVID-19.
4. Peri-luminal coronary cta AI-driven radiomics to identify vulnerable patients (CORO-CTAIOMICS)
PI: Antonio Esposito
Aim: The study aims to develop a ready-to-use AI-platform capable of providing a clinical/radiomics score of progression and occurrence of major cardiac events for patients with non-obstructive/obstructive Coronary artery disease (CAD). This will be achieved by exploiting the informative value of coronary computed tomography angiography data through the extraction of a radiomics signature describing the burden, the composition, and the inflammation of CAD. The platform will be completely automatic, leveraging machine-learning based radiomics to extract data previously not used for non-obstructive CAD patient stratification.
Neurology
1. Discovery of novel neuroprotective drugable targets and repurposed drugs to treat incurable neurodegenerative disorders
PI: Gianvito Martino
Aim: Our objective is to validate the neuroprotective properties of Bifeprunox using human iPSC-derived motor neurons and more sophisticated 3D models upon either oxidative/inflammatory or excitotoxic stress mimicking neuroinflammatory conditions. We will also evaluate the 4D expression (in time and space) of the DRD2 receptor in experimental stroke and in human stroke at various timepoints after injury. Studying Bifeprunox’s mechanism of action is intended to pave the way for a drug optimization program using in silico and in vitro approaches. The final goal of this project is to provide a small set of optimized compounds to be tested in the available cellular models.
2. Innate immune cells in multiple sclerosis – ICEMUSCLE
PI: Roberto Furlan
Aim: Due to the unclear knowledge about the conditions that give rise to disimmunity or autoimmunity in the central nervous system, this project aims to use front technologies, such asmultiparametric flow cytometry, next generation sequencing, and immunometabolic analyses, to describe the immunometabolic profile of myeloid innate immune cells, such as neutrophils, monocytes and macrophages, in people suffering from multiple sclerosis. The main goal of this project is to identify general regulatory mechanisms favoring autoimmune processes.
3. Implementing a national biobank of genetic, sporadic and prodromic Parkinson’s disease with whole genome analysis and functional assessment of polygenic inheritance by iPSC technology
PI: Vania Broccoli
Aim: The project aims to coordinate local biorepositories of Parkinson’s disease biological specimens to create a standardized and integrated national resource through the collection of additional samples from sporadic PD cases and the extension of the sampling to patients with REM sleep behavior diseases. Two hundred patients will be involved in a large campaign of whole genome sequencing, in order to identify rare genomic variants which may be associated with these diseases and to combine iPSC technology with gene editing to assess the relative impact of rare variants.
4. Artificial Intelligence applied to conventional and advanced MRI sequences for improving disease classification and prediction of clinical worsening in patients with multiple sclerosis
PI: Massimo Filippi
Aim: The aim of this project is to discover the ability of AI tools to correctly identify Multiple Sclerosis patients from healthy controls, identify MS patients at risk of disability progression and cognitive deterioration, and reduce patients suffering according to their clinical profile.
Oncology
1. Precision Medicine in patients with unresectable cholangiocarcinoma; radioembolization in combination with cisgem and Durvalumab (PM-CARE)
Aim: Evaluate the safety and efficacy of transarterial embolization in association with a combination of chemo-immunotherapy in treatment-naïve patients with liver-predominant unresectable intrahepatic cholangiocarcinoma. The study will collect valuable information on local and systemic tumor biology, immune and molecular profiles on bioptic tissue and circulating blood samples, and imaging-based biomarkers to develop personalized predictive models of therapeutic response and clinical outcome.
2. Leukemic cell and microenvironment interactions as the culprit of chronicity in CLL
Aim: Chronic lymphocytic leukemia is the most widespread leukemia among adults in Western countries, and despite therapeutic advancements with the use of novel chemo-free targeted therapies, it is still virtually incurable. This project aims to investigate the crucial pathways and molecules that are responsible for the chronic behavior of the disease and for its clinical progression in a portion of patients.
3. Developing and optimizing X-Rays mini-beam Radiotherapy
Aim: The main goal of this project is the development, optimization, dosimetry verification and testing of collimation systems for the generation of mini-beams radiotherapy (MBRT) to be delivered by a last generation image-guided small animal irradiator. The outcomes will lead to a set of devices that could be integrated within a commercial small animal preclinical research platform, and thus making them commercially available to the scientific community. The platform for MBRT will be used for preclinical experiments focused on treating glioblastoma multiform cells and animal models aiming to measure the biological effects with respect to conventional radiotherapy. The goal is to investigate MBRT’s disruptive potential to reduce toxicity, allowing an increase in the dose for radiation resistant tumors.
Endocrinology
1. Definition of a personalized signature of chronic inflammation and early aging predictive of the development of comorbidities in infertile men
PI: Andrea Salonia
Aim: To identify causal links between infertility, prevalent and incident comorbid conditions and chronic inflammation. Extensive clinical data with state-of-the art omics approaches will be applied to discover novel prognostic biomarkers/signatures in order to develop tailored prevention strategies against early aging and clinically severe comorbidities in infertile men.
2. Towards a personalized precision medicine in rare disease: tirzepatide (a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agoinst) monotherapy in patients with Wolfram syndrome type 1
PI: Lorenzo Piemonti
Aim: This project aims to develop a model of a precision-medicine-oriented Rare Diabetes Clinic, specifically dedicated to the treatment and follow-up of complex patients with Wolfram syndrome. The initiative will focus on tailoring therapeutic strategies that consider the unique genetic, metabolic, and clinical profiles of each patient. By utilizing tirzepatide as a monotherapy, we hope to evaluate its effectiveness in managing hyperglycemia and other related complications associated with this rare condition.
Gastroenterology
1. Machine Learning approach and IoT technologies to unravel the complex interaction between environmental factors and intestinal tissue homeostasis in chronic inflammatory disorders: sealing the leaky gut
PI: Silvio Danese
Aim: Using Internet-Of-Thing technologies and machine learning approaches, the project aims to identify environmental and genetic factors favoring chronic inflammation within the intestine and in peripheral organs.
2. Optimising surgical anastomosis in ileocolic resection for Crohn’s disease to reduce recurrent disease: A Randomized controlled trial comparing HANDsewn (end-TO-END or Konos) to stapled anastomosis (HAND2ED study)
Aim: Crohn’s disease (CD) is characterized by chronic intestinal inflammation. Surgery for CD is unfortunately not curative and statistics affirm that disease recurrence is common with up to 60% having endoscopic recurrence at six months. Wound healing of inverted stapled anastomosis is essentially different from handsewn anastomosis since it is associated with ulcercations at the staple line leading to systematic over scoring of CD. The project aims to randomly compare handsewn with the side-to-side stapled anastomosis in order to determine if one method is superior to the other after ileocolic resection for CD.
Nephrology-Urology
1. Dissecting novel pathways associated with hypertension and related kidney damage
PI: Paolo Manunta
Aim: In this project, we aim to deepen our knowledge of hypertension onset, also with regards to sodium sensitivity and its impact on long-term hypertension-mediated organ damage. To this end, we will employ a multidisciplinary approach that will rely on four different murine models of HT, and several well-characterized HT patient cohorts.
2. Overtaking Intra and Inter Tumoral Heterogeneity In Von Hippel-Lindau related Renal Cancer
Aim: The aim of the project is to develop standardized models for the diagnosis and molecular characterization of clear cell renal cell carcinoma in Von Hippel-Lindau syndrome through the combined use of imaging, radiomics, and multi-omics analysis.
Hematology-Immunology
1. Mitochondrial transfer as a key to disrupting vascular disease and fibrosis in systemic sclerosis
PI: Angelo Andrea Maria Attilio Manfredi
Aim: Recent studies have shown that mitochondria can be extruded from eukaryotic cells after extreme stress and can be seen as bacteria from the immune system. This causes robust inflammation and together with consistent preliminary results suggests that mitochondria are released and accumulate in the blood of patients with systemic sclerosis. The aim of this project is to obtain evidence of the following three hypothesis: 1. Mitochondria in patients' plasma represent clinical biomarkers of vascular damage and organ fibrosis; 2. Extracellular mitochondria influence the characteristics of intravascular immunity; 3. The cellular origin of circulating mitochondria influences their fate and biological action in vitro and in vivo.
Geriatrics
1. Dissecting the molecular and cellular pathophysiology of sarcopenic obesity in the elderly
PI: Patrizia Rovere Querini
Aim: Aging is associated with a progressive modification of body composition characterized by an increased adipose tissue (AT) and decreased skeletal muscle (SM) mass and function. AT-SM crosstalk often leads to obesity and sarcopenia that often coexist (sarcopenic obesity, SO). The goal of this project is to develop a multidisciplinary research project built on the hypothesis that the development of SO relies on a vicious relationship between AT and SM. This relationship involves various intra- and inter-cellular inflammatory mechanisms: this research aims to unravel these complex interconnections through three different goals: 1. disentangle the complex AT-SM interplay in vivo; 2. define prognostic biomarkers discriminating patients’ disease trajectories; 3. design innovative therapeutic approaches.
Ophthalmology
1. Early Retinal Neurodegeneration as Risk Factor, Biomarker and Pharmacological Target of Diabetic Retinopathy
Aim: The aim of this project is to verify the hypothesis that, in case of diabetic retinopathy, early retinal neurodegeneration could represent a risk factor for the subsequent development of microaneurisms as well as a potential biomarker and pharmacologic target.