Dear all,
I would like to share this opportunity for a PhD student in our laboratory for
a 3 years period.
Our team is part of the National center for scientific research (CNRS), and is
involved in quantitative systems pharmacology of monoclonal antibodies.
Below the general conditions and qualifications for the candidates.
Thanks in anticipation for circulating this opportunity.
Regards,
Nicolas Azzopardi
PhD proposal
Location : University of Tours (France)
* Informations:
Name of the supervisor: Denis Mulleman
Laboratory: CNRS UMR7292 (GICC)
Team : PATCH (PhArmacology of TherapeutiC antibodies in Human)
Co-supervisor : David Ternant
* Short title: quantitative systems pharmacology of monoclonal antibodies
in rheumatoid arthritis
* Summary:
Quantitative systems pharmacology is a mathematical approach to study the
effect of drugs in a quantitative and dynamic manner. Gathering heterogeneous
data such as in vivo , preclinical, ex vivo and clinical data, it provides a
deep biological insight into a disease pathophysiology and a holistic
understanding of the mechanisms of action of drugs, from cellular to
macroscopic levels. It helps in quantifying the factors that may improve, or
impairs, therapeutic response. Quantitative system pharmacology may contribute
in precision medicine through a sound analysis and simulation approach,
providing a basis for designing dose adjustment, according to individual
patient’s characteristics.
Inflammation, through its micro and macroscopic components, is likely to
modulate the response to monoclonal antibodies that are used in immune-mediated
inflammatory diseases. An analysis of the dose-response relationship, based on
mathematical modeling of both dose-concentration (pharmacokinetic) and
concentration-response (pharmacokinetic-pharmacodynamic or PK-PD)
relationships, should decipher and quantify the interactions between
inflammation and response to monoclonal antibodies. Building a multi scale
pathophysiologic system ( systems biology ), in combination with a
pharmacokinetic and PK-PD model, quantitative system pharmacology should help
in understanding the mechanism of action of monoclonal antibodies in
immuno-inflammatory diseases.
* Key words: Inflammation, Monoclonal antibodies, Systems biology,
Biomarkers, pharmacokinetics, PK-PD modelling, quantitative system
pharmacology, rheumatoid arthritis
* Five publications of the supervisor and co-supervisor during the last 4
years:
* Ternant D, Ducourau E, Fuzibet P, Vignault C, Watier H, Lequerré T, Le
Loët X, Vittecoq O, Goupille P, Mulleman D, Paintaud G. Pharmacokinetics and
concentration-effect relationship of adalimumab in rheumatoid arthritis. Br J
Clin Pharmacol. 2015;79:286-97.
* Ducourau E, Ternant D, Lequerré T, Fuzibet P, Le Loët X, Watier H,
Goupille P, Paintaud G, Vittecoq O, Mulleman D. Towards an individualised
target concentration of adalimumab in rheumatoid arthritis. Ann Rheum Dis.
2014;73:1428-9.
* Ternant D, Ducourau E, Perdriger A, Corondan A, Le Goff B,
Devauchelle-Pensec V, Solau-Gervais E, Watier H, Goupille P, Paintaud G,
Mulleman D. Relationship between inflammation and infliximab pharmacokinetics
in rheumatoid arthritis. Br J Clin Pharmacol. 2014;78:118-28.
* Mélet J, Mulleman D, Goupille P, Ribourtout B, Watier H, Thibault G.
Rituximab-induced T cell depletion in patients with rheumatoid arthritis:
association with clinical response. Arthritis Rheum. 2013;65:2783-90.
* Edupuganti SR, Eder V, Ternant D, Courtehoux M, Tranquart F, Goupille P,
Paintaud G, Mulleman D. F-18 fluorodeoxyglucose positron emission tomography
can detect early response to adalimumab, a tumor necrosis factor-α antagonist,
in rheumatoid arthritis: A prospective pilot study. Joint Bone Spine.
2015;82:381-3.
* Eligibility criteria:
1.
Master degree in quantitative system pharmacology
2. Acquaintance with PK-PD modelling and simulation softwares
3. Fluency with written and spoken English (mandatory)
* Selection procedure: The best-qualified applicants will be invited
locally for an interview by the Selection Board of the University.
* Submission of applications: Candidates are requested to submit their
application (cover letter + CV) to: Ms. Anne Mychak via email (
[email protected] ) or post (GICC – UMR 7292, Faculté de Médecine,
Bâtiment Vialle, 10 Boulevard Tonnellé, BP 3223, 37032 Tours Cedex 01 - FRANCE)
* Dead line for application: June 1st, 2016
* Starting date: September 2016, three years duration