POSITION: Full Professor at the Università degli Studi della Campania “Vanvitelli”
1980 Degree in Biological Sciences (110 summa cum laude), University of Naples "Federico II". 1982-1990 Postgraduate scholarship at the CNR. 1991 Researcher at the Baylor College of Medicine (Houston). 2001 Associate professor. 2002-2011 Associate Professor. 2011 Full Professor at Università degli Studi della Campania “Vanvitelli”, SSD M-EDF/01.
B. Personal Statement and Contribution to Science
Prof. A. Daniele contributed at numerous research projects granted by CNR, Ministry of Health, Region of Campania and Molise. Speaker at several national and international conferences. Prof. A. Daniele is author of 94 papers in international journals peer reviewed and referee for international journals. Prof. A. Daniele teaches several courses in the fields of General Biochemistry, Clinical Biochemistry, Genetics and Biochemistry of Nutrition. The main research activities carried out by Prof. A. Daniele are: biochemical and molecular genetic analysis of Mucopolysaccharidoses, Hyperphenylalaninemias, polycystic kidney disease; expression studies of adiponectin role in different diseases (obesity, myotonic dystrophy, chronic obstructive pulmonary disease, immune disorders, cancer), in animal models (pig and mouse); Studies of molecular effects of adiponectin administration in human cell lines (proliferation, inflammatory state and oxidative stress); molecular analysis of PKD1 and 2 in autosomal dominant polycystic kidney disease.
Recent studies shown that adipose tissue plays a major role in inflammation and immunity by producing bioactive mediators called adipokines. Amongst adipokines, adiponectin is involved in the regulation of glucose and lipid metabolism, modulating the action of insulin, and possesses anti-inflammatory properties exerting protective effects on the development of obesity-associated pathologies. The expression of adiponectin in the serum of healthy subjects is about 5-30 mg/ml, representing 0.01% of the total proteins. In patients with metabolic diseases such as obesity related diseases, adiponectin levels considerably decrease. Adiponectin circulates in the serum as oligomers of three oligomeric complexes, trimers (low molecular weight: LMW), hexamers (medium molecular weight MMW) and high molecular weight forms (HMW). Several lines of evidence suggest that oligomeric state affects the biological activity of adiponectin; indeed HMW represent the oligomers with the highest biological activity. Adiponectin plays its beneficial functions via three receptors, AdipoR1 and AdipoR2 (widely expressed in various tissues and organs) and T-cadherin, mainly expressed on endothelial cells. Our research projects are focused on the expression of total adiponectin, its oligomers and its receptors in several types of disorders: obesity and related disorders, immunological diseases, and cancer, aiming at clarifying the possible use of adiponectin as a therapeutic biomarker. Through in vitro studies on cell lines, we explore the molecular mechanisms at the basis of adiponectin regulation as well as the effects of adiponectin on cellular processes as proliferation, inflammation, oxidative stress.
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the growth of numerous cysts in the kidneys. It is the most common inherited disorder of the kidneys. ADPKD is caused by mutations in the PKD1 and PKD2 genes, transient receptor potential cation channels. Our activity is focused on the development of a rapid but reliable molecular analysis of those two genes involved in ADPKD. We are exploring a next generation sequencing approach to perform the molecular analysis of PKD1 and PKD2 genes.
A) ROLE OF ADIPONECTIN IN THE PREVENTION OF OBESITY AND METABOLIC SINDROME
Adiponectin is a protein hormone produced by adipose tissue and secreted in serum; it is involved in regulating glucose and lipid metabolism, modulating the action of insulin, possessing anti-inflammatory properties exerting protective effects on the development of associated pathologies obesity. The expression of adiponectin in the serum of healthy subjects is about 5-30 mg/ml, representing 0.01% of the total proteins. In patients with metabolic diseases such as obesity related diseases, adiponectin levels considerably decrease. Adiponectin circulates in the serum as oligomers of different weight. This adipokine is processed into at least three oligomeric complexes, trimers (low molecular weight: LMW), hexamers (medium molecular weight MMW) and high molecular weight forms (HMW). There is growing interest in the role of these complexes in metabolism and disease as several lines of evidence suggest that oligomeric state affects the biological activity of adiponectin. Indeed, HMW represent the oligomers with the highest biological activity. Adiponectin plays its beneficial functions via three receptors, AdipoR1 and AdipoR2 that belong to the family of seven transmembrane receptors and are widely expressed in various tissues and organs and T-cadherin, mainly expressed on endothelial cells. The adiponectin gene, ApM1, maps on chromosome 3 and consists of 3 exons. In obesity and related diseases, serum levels of adiponectin are reduced and its mechanism of action is altered. Our research team is concerned characterizing: a) the ApM1 gene in a population of severely obese subjects; b) adiponectin serum levels in adult and pediatric patients affected by obesity and/or related metabolic pathologies c) the molecular mechanisms of adiponectin action in obesity d) adiponectin receptors expression in adipose tissue from patients affected by obesity and subjected to bariatric surgery.
B) ROLE OF ADIPONECTIN IN LUNG AND COLON CANCER
Current epidemiological evidence suggests an association between obesity, hyperinsulinemia, and risk of several cancers. However, data on serum adiponectin expression in cancer patients are still inconclusive, decreased or unmodified levels of adiponectin have been reported. Also in vitro studies reported contrasting results; some authors found that adiponectin exerts pro-proliferative effects while others demonstrated an inhibitory role for adiponectin in several cellular models of carcinoma. Our studies explore the possibility to use adiponectin as a diagnostic and prognostic marker in lung and colon cancer. In addition, we analyze adiponectin molecular effects in terms of proliferation, apoptosis, inflammation and oxidative stress. Our data will help to understand whether adiponectin and its receptors could represent a useful tool for the follow-up of patients with lung and colon cancer strengthening a direct role of the adiponectin system in carcinogenesis.
C) 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-related functions by producing bioactive mediators called adipokines. Amongst adipokines, adiponectin has anti-inflammatory and immune-suppressive effects inhibiting the phagocytic activity of macrophages, decreasing tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 production. Common variable immunodeficiency (CVID) is a severe immunodeficiency disorder that impairs the immune system. People with CVID are highly susceptible to infection from foreign invaders such as bacteria, or more rarely, viruses and often develop recurrent infections and cancer. Multiple sclerosis is a neurological condition that affects central nervous system. It is a demyelinating disease in which nerve cells and spinal cord are damaged. This damage disrupts the ability of parts of the nervous system to communicate, resulting in a range of signs and symptoms, including physical, mental. Our research activities focus on the evaluation of total Adiponectin and HMW oligomers in CVID and multiple sclerosis patients before and after immunoglobulin infusion (routine treatment for CVID patients). In addition, we evaluate the molecular mechanisms at the basis of Adiponectin modulation in CVID by evaluating the peripheral blood leucocytes cells profiling as well as the expression of AdipoR1, AdipoR2 and T-cadherin on peripheral blood leucocytes from CVID patients before and after IG replacement therapy and in comparison, to healthy controls. In addition, since B cells are influenced by different cytokines, we will test IL-2, IL-6, IL-10, TNFa, IFNg concentrations in serum of patients and controls by Elisa test. Our study, clarifying the molecular mechanisms of adiponectin regulation in immune responses, would allow the use of this adipokine as a biomarker in the therapeutic management of immune disorder’s patients.
D) MOLECULAR ANALYSIS OF PKD1 AND2 IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited cause of kidney failure, is caused by mutations in either PKD1 (85%) or PKD2 (15%). The PKD2 protein, polycystin-2 (PC2 or TRPP2), is a member of the transient receptor potential (TRP) superfamily and functions as a nonselective calcium channel. PC2 has been found to form oligomers in native tissues it may form functional homo- or heterotetramers with other TRP subunits. ADPKD is a genetic disorder characterized by numerous cysts in the kidneys. ADPKD is caused by mutations in the PKD1 and PKD2 genes, transient receptor potential cation channels. Our activity is focused on the development of a rapid but reliable molecular analysis of those two genes involved in ADPKD. We are exploring a next generation sequencing approach to perform the molecular analysis of PKD1 and PKD2 genes to ameliorate and personalize the therapeutic protocol.
- Marta Mallardo
- Maria Ludovica Monaco
- Ersilia Nigro
- Rita Polito
1. Adiponectin expression and genotypes in Italian people with severe obesity undergone a hypocaloric diet and physical exercise program. Corbi, G., Polito, R., Monaco, M.L., (...), Daniele, A., Nigro, E. 2019 Nutrients 11(9),2195.
2. Adiponectin profile at baseline is correlated to progression and severity of multiple sclerosis. Signoriello, E., Lus, G., Polito, R., (...), Nigro, E., Daniele, A. 2019 European Journal of Neurology 26(2), pp. 348-355
3. Nutritional factors influencing plasma adiponectin levels: results from a randomised controlled study with whole-grain cereals. Polito R., Costabile G., Nigro E., (...), Daniele A., Annuzzi G. 2019 International Journal of Food Sciences and Nutrition. 2019 Oct 22:1-7.
4. Adiponectin and colon cancer: evidence for inhibitory effects on viability and migration of human colorectal cell lines. Nigro, E., Schettino, P., Polito, R., (...), De Palma, G.D., Daniele, A. 2018 Molecular and Cellular Biochemistry 448(1-2), pp. 125-135.
5. Total and high molecular weight adiponectin expression is decreased in patients with common variable immunodeficiency: Correlation with Ig replacement therapy. Pecoraro, A., Nigro, E., Polito, R., (...), Daniele, A., Spadaro, G. 2017 Frontiers in Immunology 8(JUL),895.