Name and Surname

Name and Surname: Robert Nisticò

Qualification: Associate Professor of Pharmacology

Scientific Sector: BIO/14

Contact: +390672594875

Biography:

Current position

2012- : Associate Professor of Pharmacology, Faculty of Pharmacy and Medicine, Sapienza University of Rome, Italy.

2006- : Principal Investigator at the C.E.R.C. – IRCSS S. Lucia Foundation, Rome, Italy.

2012- : Visiting Scientist at the E.B.R.I. – Rita-Levi Montalcini Foundation, Rome, Italy.

Education

1993-1999: Università Cattolica del Sacro Cuore, School of Medicine, Rome, Italy: Degree in Medicine and Surgery, cum laude.

2000-2003: Università Cattolica del Sacro Cuore, School of Medicine, Rome, Italy: Specialization in Psychiatry and Clinical Psychology, cum laude.

Academic Appointments/Research experience

2002-2005: Research fellow at the University of Bristol, MRC Centre for Synaptic Plasticity, United Kingdom.

2001-2006: Researcher of Pharmacology, Faculty of Pharmacy, University of Calabria, Italy.

2006-2012: Associate Professor of Pharmacology, Faculty of Pharmacy, University of Calabria, Italy.

Honours

2002-2003: Marie Curie Intra European Fellowship (EIF) for Life Sciences 20000

2003-2004: Marie Curie Reintegration Grant (ERG) for Life Sciences 20000

2012-2015: Honorary Special Lecturer, School of Pharmacy, University of Nottingham, United Kingdom.

Editorial activity

Member of the Editorial Board of NPG Scientific Reports, NeuroMolecular Medicine, ISRN Stroke, World Journal of Pharmacology, World Journal of Methodology, Journal of Biological Regulators and Homeostatic Agents, Journal of Pharmacology and Toxicology Research, Journal of Alzheimer’s disease (2012-2013).

2012: Guest Editor, Molecular Neurobiology, Special Issue on ‘Integrating Molecular Mechanisms with Synaptic Plasticity in Neurodegenerative Disease’.

2013: Guest Editor, Current Pharmaceutical Design, Special Issue on ‘Targeting synaptic dysfunction and neural connectivity in neurological and psychiatric disorders’.

2013: Guest Editor, Neuromolecular Medicine, Special Issue on ‘SUMOylation in neuroplasticity and neurological disorders’.

Main research activity

I am currently interested in synaptic mechanisms and, in particular, synaptic plasticity in the mammalian central nervous system. Synaptic plasticity is an essential property of the brain implicated in the development of the nervous system and underlying learning and memory processes. Alterations of these processes are involved in various neurodegenerative disorders, including Alzheimer’s disease and Multiple Sclerosis. My work is highly interdisciplinary. I use a range of electrophysiological, biochemical and imaging techniques to investigate the role of different signaling pathways in the hippocampus under normal and pathological conditions. In particular, I focus on the phenomena of long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus, a brain region important for learning and memory and cognitive processes. Over the past years, I have studied how neuroinflammation and excitotoxicity lead to impairments in LTP and memory in mice that model Alzheimer’s disease (AD) and Multiple Sclerosis (MS). These studies are of a general relevance to the field of AD and MS both for understanding the etiopathogenesis of the disease and for developing new therapies aiming to improve the cognitive symptoms.

Bibliometric indices (Scopus)

Author ID: 6701421675

In extenso publications: 91

Total citations: 1314

h-index: 22

Title of teaching module: GENERAL AND MOLECULAR PHARMACOLOGY AND TOXICOLOGY (il nome è leggermente cambiato rivedere)

Description of teaching module (teaching program):

Objectives:

The course is aimed at providing information regarding the molecular mechanisms implicated in the biological responses to drugs. The first part of the course will consist in a detailed analysis of the molecular structure of receptors and the cellular and molecular mechanisms implicated in the pharmacological responses. The second part will be focused on cellular and molecular mechanisms of toxicity, regulatory guidelines and experimental approaches for the safety of drugs. The third part is related to pharmacokinetics.

Program:

General and Molecular Pharmacology

Pharmacodynamics: The pharmacological concept of potency, efficacy, pD2, pA2. Agonists, antagonists, partial agonists and inverse agonists. Factors affecting pharmacodynamic variability and the role of this variability in drug efficacy and toxicity.

Receptors: Classification, structural, molecular and functional organization, pharmacological modulation. Regulation of receptor function: desensitisation, up regulation, down regulation.

Ionotropic receptors: Tissue and subcellular distribution. Molecular organization. Ionic selectivity. Pharmacological modulation.

Metabotropic receptors: Classification. Molecular organization. Ligand binding sites. Mechanisms of interaction with G proteins. Molecular organization and function of heteromeric G proteins. Effector mechanisms: adenylate cyclase and cAMP, phospholipase C and phosphinositides cycle, MAP kinase cascade. Scaffolding proteins: localization and functions.

Methods for the study of membrane receptors: Receptor binding studies on membranes and tissues (receptor autoradiography). Methods for the analysis of G protein coupling to receptors. Principles of immunohistochemistry and electrophysiology.

Protein kinases and their role in signal transduction: Molecular structure and mechanism of action of protein kinases A, C, calcium/calmodulin-dependent, MAPK. GSK: G protein coupled receptor kinases. Pharmacological modulation of protein kinases. Protein phosphatases. Calcinueurin and immunosuppressant drugs. Role of phosphorylation in the modulation of receptor function. Regulation of intracellular calcium homeostasis: Structure and function of calcium channels, pumps and transporters localized on the cell membrane. Voltage-dependent calcium-channels: classification, molecular organization, voltage sensor, ionic selectivity, pharmacological modulation. Na+/K+-ATPase, Na+/Ca2+ exchanger and cardioactive glycosides. Intracellular calcium store, ryanodine and IP3 receptors, endogenous and pharmacological modulators. Cytosolic proteins implicated in calcium binding.

Sodium channels: Voltage-dependent sodium channels: molecular organization, functions, voltage sensor, opening and inactivating mechanisms, cellular localization: cytoskeleton anchoring sites, modulation by drugs and toxins. Epithelial sodium channels: molecular organization and modulation by potassium spare diuretics.

Potassium channels: Molecular and functional classification. Voltage-gated channels, ATP-dependent channels, GIRKS, inward rectifiers, calcium-activated channels. Pharmacological modulation of potassium channels.

Chloride channels: Molecular organization and function of CIC and CFTR channels.

Neurotransporters: Molecular structure, activation mechanisms and pharmacological modulation of neurotransporters: membrane Na+/K+-dependent transporter for EAA, membrane Na+/Cl—dependent transporters for GABA and monoamines, vesicular H+-dependent transporters for amino acids and acetylcholine.

Catecholaminergic transmission: Biosynthesis, vesicular storage, metabolic degradation and reuptake. α e β adrenergic and dopaminergic receptors: molecular organization, function, signal transduction mechanisms, pharmacological modulation.

Cholinergic transmission: Biosynthesis, intracellular storage and metabolism of acetylcholine. Cellular localization, function and structural features of choline acetyl transferase and cholinesterases. Classification, molecular organization and mechanisms of activation of nicotinic and muscarinic receptors.

Serotonergic transmission: Biosynthesis, metabolism and reuptake of serotonin: pharmacological modulation. Classification, function and modulation of serotonin receptors.

GABAergic transmission: Synthesis, degradation and reuptake of GABA: pharmacological modulation. GABAA, GABAB and GABAC receptors: molecular organization, mechanisms of receptor activation and modulation.

Excitatory amino acid transmission: Synthesis, vesicular storage and transport of glutamate. Ionotropic and metabotropic receptors for EEA: classification, molecular organization, mechanisms of activation and pharmacological modulation.

Nitric oxide: Roles, biosynthesis, NOS synthase: isoforms, regulation and pharmacological modulation.

Opioid system: Roles biosynthesis and metabolism of endogenous opioids. Opioid receptors: molecular organization, mechanisms of receptor activation and pharmacological modulation.

Cannabinoids: Roles, biosynthesis and metabolism of endocannabinoids. Cannabinoid receptors: molecular organization, mechanisms of receptor activation and pharmacological modulation.

Toxicology

Introduction to toxicology; different areas of toxicology. Classification of Toxic effects: immediate versus delayed toxicity, reversible versus irreversible toxic effects, local versus systemic toxicity.

Dose-Response relationship. Variation in toxic responses: selective toxicity, species differences; individual differences in response.

Toxicokinetics: absorption, distribution, and excretion of toxicants; biotransformation of xenobiotics.

Mechanisms of toxicity. Cellular toxicity: apoptosis and necrosis.

Pharmacokinetics

Scope and aims of pharmacokinetics. Utility of pharmacokinetics in pharmacotherapy and drug development.

Pharmacokinetic parameters (Ke, Clearance, Vd, t1/2). Steady-state. Relationship between persistence in the body and effect. Passage through biological membranes, parameters influencing diffusion. Cell barriers. Entity and rate of absorption, bioavailability. Absorption routes. Factors influencing oral absorption. Pre-systemic elimination. Binding to plasma proteins. Pharmaco-toxicological consequences of plasma protein binding displacement. Accumulation and storage tissues. Renal and biliary excretion. Excretion of drugs with milk. Dose-concentration relationship, saturation kinetics. Kinetic variability: influence of genetic factors, interactions, pathologies.

Metabolism of drugs. General features of biotransformation reactions. Variability of metabolising enzymes. Activating and detoxifying reactions. Phase I and II enzymes and reactions. Cytochrome P450. Cytochrome P450 isoenzymes. Enzymatic induction: mechanisms and kinetics, pharmacological and toxicological consequences. Enzymatic inhibition: mechanisms and kinetics, pharmacological and toxicological consequences, main inhibitors of CYP450. Genetic polymorphism of metabolising enzymes.

References

Goodman and Gilman: The pharmacological basis of therapeutics, XI ed. McGraw-Hill

Hammond, Cellular and Molecular Neurophysiology, III ed. Academic Press

Casarett & Doull's Toxicology: The Basic Science of Poisons, VII ed. McGraw-Hill