Managerial evolution of a research scientist from 1997-2003:
- Junior Research Scientist from 1997-1999 developing assays for D3 receptor binding and MAP kinase activation, and characterizing the D3 receptor antagonist S33084.
- Research Scientist from 1999-2001 managing a team of 2-4 technicians and developing new assays for G protein activation and PLC activity.
- Group Leader from 2001-2003 managing a team of 5 people and a drug screening program on 20 GPCRs, as well as studies on receptor regulation and signaling in cell lines and brain tissue.
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
GPCRs are the most dynamic and most abundant all the receptors. The G protein-coupled receptor (GPCR) superfamily comprises the largest and most diverse group of proteins in mammals. GPCRs are responsible for every aspect of human biology from vision, taste, sense of smell, sympathetic and parasympathetic nervous functions, metabolism, and immune regulation to reproduction. GPCRs interact with a number of ligands ranging from photons, ions, amino acids, odorants, pheromones, eicosanoids, neurotransmitters, peptides, proteins, and hormones.
Nevertheless, for the majority of GPCRs, the identity of their natural ligands is still unknown, hence remain orphan receptors.
The simple dogma that underpins much of our current understanding of GPCRs, namely,
one GPCR gene− one GPCR protein− one functional GPCR− one G protein −one response
is showing distinct signs of wear.
Molecular, physiological and pathophysiological analysis of the β₂-adrenorece...Michael Reinartz
Slides of my thesis defence on 14th of July 2015.
As part of my PhD thesis, I analyzed β₂-adrenoceptor-mediated signal transduction. The β₂-adrenoceptor is pathophysiologically relevant e.g. in case of bronchial asthma.
My studies add to the receptor-pharmacological concept of functional selectivity. Functional selective (or biased ) ligands may be exploited to achieve highly selective drug effects and, thus, improved drug safety with less adverse effects.
Further, my studies included a collaboration with allergy geneticists. Here we linked genomic and pharmacological profiling of the β₂-adrenoceptor in 60 volunteers. Such pharmacogenomical data may help to stratify treatment groups and create a basis for a more effective, personalized asthma therapy.
(German title: "Molekulare, physiologische und pathophysiologische Analyse des β₂-Adrenorezeptors")
Introduction to the phenomenon of Biased agonism with few examples of receptors exhibiting this phenomenon and an example of drug developed on the basis of biased agonism.
Deepak Pandey, PG Pharmacology, VMMC
Nicholas Young, Sphingosine 1-phosphate Receptor Subtype Influence over Gliob...Nicholas Young
My talk presenting my thesis work per invitation of Research and Development Division of Genzyme Corporation to the Lipid Storage Disorders Department. October 5, 2007. Boston, MA: "Sphingosine 1-phosphate Receptor Subtype Influence over Glioblastoma Multiforme Pathology". My PhD was earned through the Integrated Biomedical Sciences, September 2007, The Ohio State University, College of Medicine Columbus, OH. Area of focus for my PhD: Biochemical and Molecular Disease Mechanisms. Dissertation title: Sphingosine 1-phosphate Receptor Subtype Influence Over Glioblastoma Multiforme Malignant Behavior"
Molecular, physiological and pathophysiological analysis of the β₂-adrenorece...Michael Reinartz
Slides of my thesis defence on 14th of July 2015.
As part of my PhD thesis, I analyzed β₂-adrenoceptor-mediated signal transduction. The β₂-adrenoceptor is pathophysiologically relevant e.g. in case of bronchial asthma.
My studies add to the receptor-pharmacological concept of functional selectivity. Functional selective (or biased ) ligands may be exploited to achieve highly selective drug effects and, thus, improved drug safety with less adverse effects.
Further, my studies included a collaboration with allergy geneticists. Here we linked genomic and pharmacological profiling of the β₂-adrenoceptor in 60 volunteers. Such pharmacogenomical data may help to stratify treatment groups and create a basis for a more effective, personalized asthma therapy.
(German title: "Molekulare, physiologische und pathophysiologische Analyse des β₂-Adrenorezeptors")
Introduction to the phenomenon of Biased agonism with few examples of receptors exhibiting this phenomenon and an example of drug developed on the basis of biased agonism.
Deepak Pandey, PG Pharmacology, VMMC
Nicholas Young, Sphingosine 1-phosphate Receptor Subtype Influence over Gliob...Nicholas Young
My talk presenting my thesis work per invitation of Research and Development Division of Genzyme Corporation to the Lipid Storage Disorders Department. October 5, 2007. Boston, MA: "Sphingosine 1-phosphate Receptor Subtype Influence over Glioblastoma Multiforme Pathology". My PhD was earned through the Integrated Biomedical Sciences, September 2007, The Ohio State University, College of Medicine Columbus, OH. Area of focus for my PhD: Biochemical and Molecular Disease Mechanisms. Dissertation title: Sphingosine 1-phosphate Receptor Subtype Influence Over Glioblastoma Multiforme Malignant Behavior"
1. Managerial evolution
1997-1999: Junior Research Scientist (Cadre Technique), one technican.
Development of [35S] GTPS binding at D3 receptors and demonstration of MAP kinase activation (western
blot) by D3 receptors involving an atypical PKC and the PI3-Kinase.
Characterisation of S33084 and its tritiated radioligand, a highly selective and potent D3 receptor antagonist.
Miniaturisation of binding protocols in 96 well format.
1999-2001: Research Scientist (Cadre de Recherche), management of 2-4 technicians.
Development of antibody capture assay as a measure of activation of specific G protein subtypes, employing
[35S] GTPS binding coupled to Scintillation Proximity Assay (SPA) detection at muscarinic receptors.
Development of a new PLC activity assays at serotonin 5-HT2A/2B/2C receptors and at 1A adrenoceptors.
Role of 2 adrenoceptors in actions of antiparkinson drugs. Antagonist action of piribedil at 2 adrenoceptors
coupled to MAP-kinase activation.
Characterisation of pindolol and atypical antipsychotic agents at 5-HT1A receptors coupled to MAP-Kinase.
2001-2003: Group Leader (Chef d'Etudes Scientifiques), team with 5 people (one Ph D).
Management of a team comprising one Ph.D., four technicians and one people in Master degree
Management of drug screening programme and related database on 20 human and native rat G protein
coupled receptors and re-uptake sites expressed in different cell lines or tissues.
Management of culture of 15 cell lines (CHO, IM9, U373-MG, SH-SY5Y…).
Chronic studies in rat with several antidepressants: Impact on adrenergic and 5-HT2A receptor level.
Functional ([35S]GTPS) autoradiography by in situ detection of G protein activation on rat brain section.
Studies of agonist-directed trafficking of signalling at dopamine (D1, D2S/2L, D3), serotonin (5 HT1A/1B, 5
HT2A/2B/2C), adrenergic (1A/1B, 2A) and muscarinic (M1, M4) receptors coupled to specific G proteins
(Gs, Gi3, Go, Gq) in cell lines and native rat tissues (hyppocampal, cortex, striatum), employing antibody
capture / SPA technology.
ERK1/2 activation profiles of ligands at dopamine (D2L, D3), serotonin (5 HT1A, 5 HT2C), adrenergic (2A)
and tachykinin (NK1) receptors. Development of ERK1/2 activation by ELISA in 96 well format.
Characterisation of affinity and efficacy of antiparkinson agents at 20 receptor subtypes
Listed information on published compounds at Servier
S16924 Potential 'atypical' antipsychotic agent with D2 and 5-HT1A receptor activities. Phase II (Discontinued).
S18327 Potential 'atypical' antipsychotic agent with D2 and 2 adrenoceptor activites. Phase I (Discontinued).
S33084 Potent and selective D3 receptor antagonist for treatment of schizophrenia. Pre-clinical research.
S33138 Dopamine D3 and D2 receptor antagonist for treatment of schizophrenia. Phase III (Discontinued).
S33592 Dopamine D2/D3 receptor low partial agonist: candidate for treatment of schizophrenia. Pre-clinical research.
S33005 Potent and selective SNRI with potential antidepressant properties. Pre-clinical research.
S35966 Potential antidepressant agent. Potent SNRI and antagonist at 2 adrenoceptors. Pre-clinical research.
S20098 VALDOXAN®
, launch in 2010. Antidepressant with dual melatonin 5-HT2C receptor properties.
S37245 Potential antidepressant/anxiolytic with partial agonist properties at 5-HT1A receptors. Pre-clinical research.
S32504 Selective dopamine D3 versus D2 agonist for Parkinson's disease or depression. Pre-clinical research.