Aurora Daniele
POSITION: Full Professor of Methods and Teaching of Motor Activities (M EDF/01), at the School of Medicine and Surgery of the University of Naples Federico II and PI at CEINGE-Advanced Biotechnologies
Principal Investigator of the Research Laboratory, at CEINGE-Advanced Biotechnologies, which deals with the study of genetic pathologies such as Mucopolysaccharidosis, Polycystic Kidney Disease and Polycystic Liver Disease. Author of approximately 150 articles published in international scientific journals, Prof. A. Daniele actively participates as a speaker and/or moderator in various international and national conferences. Furthermore, she has contributed to numerous research studies funded by international, national and regional projects. During her career she attended relevant Italian university institutions (Turin, Molise, Vanvitelli) and foreign ones such as the Baylor College of Medicine in Houston.
Daniele has conducted research and diagnostic activities aimed at studying the molecular basis of various hereditary genetic diseases. She is currently involved in the identification, in patients and their relatives, of the molecular defects underlying polycystic kidney disease, polycystic liver disease (molecular analysis of the PKD1 and 2 genes in autosomal dominant polycystic kidney disease) and the analysis biochemistry of glycosaminoglycans in the urine of patients affected by Mucopolysaccharidosis. Furthermore, she studies the role of adiponectin in various human diseases (obesity, myotonic dystrophy, chronic obstructive pulmonary disease, immune disorders, cancer), in animal models (pig and mouse) and in cellular models.
Different literature data indicate that there may be a crosstalk between adipose tissue and various chronic diseases probably supported by the secretion of adipokines, hormones which can regulate proliferation, activation and secretory activity of cells. Among adipokines, adiponectin, is one of the main adipokines secreted by adipocytes that circulate as oligomers of different molecular weight: low (LMW), medium (MMW) and high molecular weight (HMW) (9). These latter are the oligomers believed to be the most biologically active (10). Circulating levels (serum range normal: 2-30 ug/ml) are modulated by various genetic, anthropometric, hormonal, inflammatory, dietary and pharmacological factors. Indeed, adiponectin is inversely related to BMI, hyperglycaemia, and inflammatory cytokines. Functionally, adiponectin possesses insulin sensitizing, anti-atherogenic, immune suppressive and anti-inflammatory properties. The biological functions are mediated by three receptors, AdipoR1, AdipoR2 and T-cadherin, ubiquitously distributed throughout the body.
Polycystic kidney disease (PKD) is the most common genetic cause of kidney failure; PKDs include a vast phenotypic spectrum of clinically and genetically heterogeneous diseases that include autosomal dominant forms (ADPKD), autosomal recessive forms (ARPKD) and various atypical forms that can have autosomal dominant and/or recessive inheritance. Our activity is focused on molecular analysis carried out using an NGS panel including 63 genes selected in collaboration with the Nephrology department of the University of Naples Federico II. Patients in whom the genetic cause of the disease is not identified are further characterized using MPLA analysis in order to identify the presence of deletions/duplications in the PKD1, PKD2 and PKHD genes.
ROLE OF ADIPONECTIN IN THE PREVENTION OF OBESITY AND METABOLIC SYNDROME
Adiponectin is a protein hormone produced by adipose tissue and secreted into the serum; it is involved in the regulation of glucose and lipid metabolism, in the modulation of insulin action, it has anti-inflammatory and antiatherosclerotic properties, exerting protective effects on the development of obesity-related pathologies. There is growing interest in the role of these complexes in metabolism and obesity, as several lines of evidence suggest that the oligomeric state influences the biological activity of adiponectin. Adiponectin exerts its beneficial functions through three receptors, AdipoR1 and AdipoR2 which belong to the family of seven transmembrane receptors and are widely expressed in various tissues and organs and T-cadherin, expressed mainly on endothelial cells. In obesity and related diseases, serum levels of adiponectin are reduced and the mechanism of action of the protein itself is reduced or altered. Our research group is responsible for characterizing: a) the ApM1 gene in a population of severely obese subjects; b) serum adiponectin levels in adult and pediatric patients suffering from obesity and/or related metabolic diseases; c) the molecular mechanisms of action of adiponectin in obesity and d) the expression of adiponectin receptors in the adipose tissue of patients with obesity undergoing bariatric surgery.
ROLE OF ADIPONECTIN IN LUNG AND COLON CANCER
Adipose tissue is an endocrine organ that secretes a variety of hormones known as adipocytokines. Epidemiological evidence suggests an association between obesity, hyperinsulinemia and the risk of several types of cancer. However, data regarding adiponectin in the serum of cancer patients are conflicting, reporting both high, low and unchanged adiponectin levels. In vitro studies have also reported conflicting results: some authors have reported that adiponectin exerts pro-proliferative effects, while others have demonstrated an inhibitory role in several cellular models of carcinoma. Our studies are aimed at characterizing the molecular mechanism through which adiponectin exerts its effects in terms of proliferation, apoptosis, inflammation and oxidative stress in cellular models, reinforcing a direct role of adiponectin in carcinogenesis.
ROLE OF ADIPONECTIN IN IMMUNE SYSTEM DISORDERS
Adipose tissue is an active organ involved not only in energy homeostasis, but also in inflammatory and immune processes. Adiponectin has anti-inflammatory and immunosuppressive effects that inhibit the phagocytic activity of macrophages, decreasing the production of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL)-6. Our research activities focus on the evaluation of total adiponectin and its oligomers in patients suffering from common variable immunodeficiency (CVID), a severe immunodeficiency disorder that compromises the immune system, and in patients affected by multiple sclerosis, a neurological condition demyelinating in which nerve cells and the spinal cord are damaged. Furthermore, our studies focus on the molecular mechanisms underlying adiponectin modulation in CVID and multiple sclerosis by evaluating the expression of AdipoR1, AdipoR2, and T-cadherin on peripheral blood leukocytes obtained from patients. Furthermore, since the immune system is influenced by several cytokines, evaluation of the expression of IL-2, IL-6, IL-10, TNF, and IFN in the serum of patients and controls can provide useful information related to adiponectin and cytokines. Our studies will clarify whether adiponectin can represent a biomarker in the therapeutic management of these patients.
MOLECULAR DIAGNOSIS AND IDENTIFICATION OF NOVEL PATHOGENIC VARIANTS IN A LARGE COHORT OF ITALIAN PATIENTS AFFECTED BY POLYCYSTIC KIDNEY DISEASES
Polycystic Kidney Diseases (PKDs) consist of a genetically and phenotypically heterogeneous group of inherited disorders characterized by numerous renal cysts. PKDs include autosomal dominant ADPKD, autosomal recessive ARPKD and atypical forms. We analyzed 500 Italian patients using an NGS panel of 63 genes, plus Sanger sequencing of exon 1 of the PKD1 gene and MPLA (PKD1, PKD2 and PKHD1) analysis. With our analysis strategy, we achieved a detection rate of approximately 70% by identifying patients with pathogenic/likely pathogenic mutations in dominant genes and patients with mutations in recessive genes. PKD1 and PKD2 were found to be the most mutated genes; but we have identified mutations in very rare genes such as UMOD, PMM2, HNF1beta and GANAB. Among the recessive genes, PKHD1 appears to be the most frequently mutated. An accurate and early molecular diagnosis is essential to adopt the appropriate therapeutic protocol and represents a predictive factor for family members.
- Ersilia Nigro (professore associato - l'Università degli Studi della Campania “Vanvitelli”)
- Daniela D'Arco (collaboratrice CEINGE per la diagnostica della malattia del rene policistico)
- Marta Mallardo (assegnista di ricerca in Scienze biomolecolari – Università degli Studi di Napoli Federico II)
- Francesca Argentino (dottoranda in Teoretical and Applied Neuroscience - Università degli Studi di Camerino)
- Nigro E, Amicone M, D'Arco D, Sellitti G, De Marco O, Guarino M, Riccio E, Pisani A, Daniele A. Molecular Diagnosis and Identification of Novel Pathogenic Variants in a Large Cohort of Italian Patients Affected by Polycystic Kidney Diseases.Genes (Basel). 2023, 8;14(6):1236.
- Riccio E, Imbriaco M, Daniele A, Iaccarino G, Pisani A. The Case | A patient with autosomal dominant polycystic kidney disease with an atypical kidney magnetic resonance image. Kidney Int. 2023,104(3):625-626.
- Mallardo M, Scalia G, Raia M, Daniele A, Nigro E. The Effects of Adiponectin on the Behavior of B-Cell Leukemia Cells: Insights from an In Vitro Study. Biomedicines. 2023;11(9):2585
- Nigro E, D'Agnano V, Quarcio G, Mariniello DF, Bianco A, Daniele A, Perrotta F. Exploring the Network
- Nigro E, Mallardo M, Amicone M, D'Arco D, Riccio E, Marra M, Pasanisi F, Pisani A, Daniele A. Exploring Adiponectin in Autosomal Dominant Kidney Disease: Insight and Implications.Genes (Basel). 2024 Apr 11;15(4):484. doi: 10.3390/genes15040484. PMID: 38674417 Free PMC article.
- Mallardo M, Daniele A, Musumeci G, Nigro E. A Narrative Review on Adipose Tissue and Overtraining: Shedding Light on the Interplay among Adipokines, Exercise and Overtraining. Int J Mol Sci. 2024 Apr 6;25(7):4089. doi: 10.3390/ijms25074089.