Staff:

Mohamad Maghnie, Full Professor
Angelo Ravelli, Full Professor
Pasquale Striano, Full Professor
Luca Antonio Ramenghi, Full Professor (tenure-track)

Claudio Bruno, Associate Professor
Alessandro Consolaro, Associate Professor
Natascia Di Iorgi, Associate Professor
Clara Malattia, Associate Professor
Stefano Volpi, Associate Professor

Marta Bassi, Fixed-term Researcher 
Giuseppa Patti, Fixed-term Researcher 
Federica Trucco, Fixed-term Researcher 
 

Main research topics:

The pediatric and endocrinology clinic is a reference center for research on rare endocrinological, skeletal, and metabolic diseases, with international collaborations that integrate European research networks (ENDOERN, BONDERN, METAB ERN), providing an important platform for the exchange of scientific knowledge and access to advanced resources. The research objectives are to consolidate its position as a reference point for innovation in the early diagnosis and treatment of rare pediatric diseases, improving the quality of life of patients through personalized therapeutic solutions and a multidisciplinary approach.

The main areas of research include:

1. Rare endocrine diseases: Adrenal disorders, calcium and phosphorus homeostasis disorders, genetic metabolic disorders related to glucose and insulin, diabetes mellitus, endocrine syndromes with genetic tumors, genetic syndromes related to growth and obesity, pituitary disorders, disorders of sexual development and maturation, and thyroid disorders. Research in these areas focuses on identifying biomarkers for early diagnosis, developing innovative treatments, and understanding the underlying genetic mechanisms.

2. Rare skeletal diseases and calcium-phosphorus homeostasis: Skeletal dysplasias and rare bone diseases (osteogenesis imperfecta, genetic and non-genetic rickets), primary and secondary osteoporosis are areas of diagnostic and therapeutic innovation. Research focuses on the development of innovative diagnostic and therapeutic approaches for the management of alterations and complications, with the aim of improving associated risk factors and patients' quality of life.

3.Metabolic diseases: The aim is to further research into rare metabolic diseases of intermediate metabolism and lysosomal storage disorders. Innovative diagnostic methods will be explored through combined biochemical and genetic neonatal screening (a patent for the second-level test was filed in 2025), as well as advanced therapies such as gene therapy and enzyme replacement therapies.

Research activities in endocrine, skeletal, and metabolic diseases can be summarized in the following areas:

-Genotyping projects: Studies are underway to identify genes associated with endocrine, metabolic, and skeletal diseases through neonatal genomic screening and early postnatal diagnosis.

-Clinical trials: Clinical studies and trials are underway and planned in the three areas of the above-mentioned diseases, with the aim of testing new innovative therapies in collaboration with European research partners.

-Use of biobanks: Programs are underway to collect biological samples from patients with rare diseases for the study of biomarkers and to facilitate research in the field of endocrine, skeletal, and metabolic diseases.

-Rare disease registries: Projects are underway on genetic diseases such as rasopathies and genetic obesity.

-International collaborations: Collaborations and projects with European consortia and registries are ongoing.

Third Mission Activities: Organization and participation in conferences, workshops, or meetings with events dedicated to citizens, students, and families on the occasion of world days (obesity, diabetes, thyroid, rare diseases, and others).

4. Rheumatic diseases, whose activities include:

- defining the most effective and cost-effective strategies for the treatment of children with chronic rheumatic diseases, in particular identifying the most appropriate time to introduce biotechnological therapies;

- development and validation of standardized clinical measures for assessing the outcome of children with juvenile idiopathic arthritis and juvenile dermatomyositis;

- development and validation of standardized tools for self-assessment by patients with chronic pediatric rheumatological diseases (or their guardians), in order to optimize both access to National Health System services and remote patient monitoring;

- creation of an integrated multi-omic model for understanding the pathogenesis of juvenile idiopathic arthritis with positive antinuclear antibodies;

- evaluation of diagnostic criteria and measurement of disease activity in patients with juvenile-onset Sjögren's syndrome

- development and validation of a multidimensional approach to evaluate the effectiveness of therapy in patients with juvenile idiopathic arthritis;

- definition of a diagnostic pathway and therapeutic strategy for patients with juvenile fibromyalgia and complex regional pain syndrome;

- clinical characterization of disease and development of new diagnostic and therapeutic strategies in patients with known autoinflammatory syndromes and immunodeficiencies;

- molecular and phenotypic characterization of new autoinflammatory diseases and immunodeficiencies;

- outcome assessment of patients with ARPC1B immunodeficiency treated conservatively or with bone marrow transplantation through collaboration between European (ESID) and North American (CIS) societies for patients with immunodeficiencies.

- use of induced pluripotent stem cells and gene editing using Crispr/Cas9 for the study of genetic diseases of the immune system and the development of preclinical models for gene therapy;

- Study of the role of inflammation in SARS-CoV2 infection and in the multisystem inflammatory syndrome related to COVID-19;

- Study of the role of inflammation in the pre-transplant conditioning of hematopoietic stem cells.

5. Neuromuscular diseases, whose main lines of research concern muscle diseases, neurodegenerative diseases, and genetic epilepsies:

- experimentation with new pharmacological therapeutic approaches in second motor neuron diseases and in myopathies and primary muscular dystrophies;

- identification of disease-specific genetic factors and biomarkers using metabolomics and proteomics approaches in muscular dystrophies and spinal muscular atrophies

- identification of new disease genes and new pathogenic mechanisms in hyperCKemias and primary myopathies;

- analysis of the pathogenic mechanisms of the neurodegenerative disease “hypomyelinization with congenital cataracts (HCC)” caused by a defect in the iccin molecule;

- identification of genetic factors associated with childhood epilepsy;

- identification of genetic factors associated with drug response and adverse events in childhood epilepsy through association studies and genomic sequencing;

- cellular reprogramming of human fibroblasts into nerve cells through the development of pluripotent stem cells for the study of pathogenic mechanisms of genetically determined epilepsy.

6. Pediatric neurology. The main lines of research are developed in the following seven areas:

1) Epilepsy: In collaboration with the Genetics, Neuroradiology, and Neurosurgery departments and with national and international institutes, quantitative and qualitative structural and functional analysis studies are underway for focal epilepsy in children; studies to identify new potential genetic variants related to focal epilepsy; and studies on the application of new minimally invasive surgical techniques (MRg-LiTT) for the treatment of focal epilepsy. Further activities have been carried out within the ERN EpiCare network, the MNESYS project, LICE (Italian League Against Epilepsy), and the International League Against Epilepsy, such as the development of new national guidelines for status epilepticus.

2) Sleep disorders: Studies are underway on the macrostructure and microstructure of sleep and the sleep-wake cycle in children with psychiatric disorders or psychopathological traits, neurodevelopmental disorders, and Rett syndrome; a study of neuropsychological aspects in patients with narcolepsy; a study of sleep and circadian rhythm in pediatric-onset epilepsy and in subjects with hypothalamic dysfunction. In addition, in collaboration with the Neonatology Unit, a study on sleep in premature infants is underway.

3) Autism: A project is underway for the observation and early identification of individuals at risk of developing an autism spectrum disorder (ASD) and their families. In collaboration with the Medical Genetics department, an analysis of rare and common variants as the oligogenic biological basis of the complex phenotype is underway, which has led to the identification of new genes. Finally, a randomized clinical trial is underway to evaluate the efficacy, safety, and tolerability of a new drug in patients with ASD.

4) Rare neurological diseases: Several research projects are underway in the field of early-onset hereditary neuropathies and neuroradiological characterization of CMT1A in collaboration with the Neurology Department of DINOGMI. A research project is underway on cells from patients with rare congenital myopathy. A trial is underway for patients under the age of 18 with myasthenia gravis. Two studies funded by DINOGMI are underway on the reanalysis of exomes from patients with neuromuscular diseases and on the application of mRNA sequencing from muscle biopsies, including an international collaborative genomics and proteomics study to resolve a complex case of PPP1R21opathy.

In collaboration with the Bambino Gesù Pediatric Hospital, a project funded by the Ministry of Health is underway on the creation of tubulinopathy models using iPSCs and Drosophila melanogaster. A multicenter retrospective study is underway in patients with Aicardi-Goutières syndrome treated with JAK inhibitors. Pharmacological studies and outcome/natural history measures are underway on alternating hemiplegia and Lesh-Nyan syndrome, as well as a single-center case series study and characterization of the muscle phenotype in patients with Bosch-Boonstra-Shaaf optic atrophy.

5) Neuroimmunology: A national multicenter study on immune-mediated neurological diseases is under development, in particular a study on anti-N-methyl-D-aspartate receptor antibody encephalitis and anti-glutamic acid decarboxylase antibody limbic encephalitis. A study is underway on subjects with Opsoclonus-Myoclonus and PANS/PANDAS. In addition, a research project has been launched to identify early markers in pediatric patients with multiple sclerosis.

6) Psychiatry and Psychopharmacology: Research in this area is strengthened by collaborative networks such as PREP-KIDS2 for the study of non-suicidal self-injury and attention deficit/hyperactivity disorder through prospective observational clinical studies. Genetic research on mood disorders and very early-onset schizophrenia and high-risk mental states has been implemented in collaboration with the Psychiatry and Genetics departments. Pharmacogenetic and pharmacogenomic studies are underway on the side effects of neuroleptic and anticonvulsant drugs commonly used in pediatric/adolescent clinical practice.

7) Neurophysiology: A doctoral project is underway on multimodal methods for identifying the epileptogenic zone in subjects undergoing stereo EEG, and other studies are being conducted in collaboration with doctoral students in bioengineering on epileptic abnormalities in REM and non-REM sleep using intracerebral electrodes and on the bioengineering analysis of the mechanisms that determine thethe evolution of infraclinical paroxysms into epileptic seizures based on intracerebral electrode signals. A project is being launched to record and analyze EEG and stereo EEG signals during anesthesiological procedures.

6. Neonatology and perinatal medicine recognizes the following lines of research:

Studies of genetics, epigenetics, and omic sciences in correlation with evaluation using experimental transfontanellar ultrasound methods (dedicated experimental equipment), Brain MRI for high-grade preterm infants and term encephalopathic infants at risk of altered neurological development (very low birth weight preterm infants < 1500 grams (VLBW), term infants with asphyxial and non-asphyxial neonatal encephalopathy) and prognostic elements. Creation of big data banks of preterm patients with fetal, neonatal, and long-term neurological follow-up data. MRI studies of brain connectivity in relation to different modes of enteral and parenteral nutrition (different lipid formulas used).

Studies of brain maturation in preterm infants using EEG and neonatal sleep studies. Studies with CGM (Continuous Glucose Monitoring) to investigate euglycemia in infants at risk of hypoglycemia (children of diabetic mothers, macrosomic infants, and particularly preterm infants). Studies of lung ultrasound and visceral fat deposition in VLBW infants according to IUGR patterns. Autopsy studies on highly preterm fetuses and newborns “at the limit of viability” with high mortality rates to better identify the causes. Placental pathology and prematurity. Studies on neonatal care during hospitalization in the NICU to improve outcomes.