PHAR20100 Medicine Module leader

BSc Pharmaceutical Sciences Director

Post-Graduate Tutor

Alain Pluen – a physical chemist by training – is a Senior Lecturer within the Division of Pharmacy and Optometrics. Alain joined the then School of Pharmacy in 2000 and has been pursuing his research effort on i) transport and/or delivery of novel medicines and 2) the study the protein-protein interactions espectially aggregation in solution to understand issues related to biopharmaceuticals formulation and cells.  This is carried out using bioimaging techniques (confocal microscopy, Raster Image Correlation Spectroscopy or Fluorescence Correlation Spectroscopy) as well as light scattering (DLS, SLS). Previously Alain did his post-graduate studies at the Institut Charles Sadron – Centre de Recherche sur les Macromolecules, (CNRS UPR 22, Strasbourg, France) where he studied the mechanisms of transport of macromolecules (single stranded DNA) in gels to improve sequencing (EU Biomed 1). Then in 1997, he joined the team of Prof. R.K. Jain at the Massachusetts General Hospital - Harvard Medical School as a post-doctoral research fellow. In this biomedical engineering laboratory and in collaboration with Dr. David Berk, he started to study the relation between the tumour microenvironment and the transport hindrance of novel medicines i.e. antibodies, protein, peptides or liposomes. In September 2000, he joined the then School of Pharmacy and Pharamceutical Sciences.

Member of the Royal Society of Chemistry

Fellow of the Higher Education Academy

Member of the Academy of Pharmaceutical Sciences

• 1996 Ph.D. Polymer Physical Chemistry - University of Strasbourg, France
• 1992 M.Sc. Physical Chemistry - University of Strasbourg, France
• 1991 B.Sc. Physical Chemistry - University of Strasbourg, France

UG teaching

• Medicine modules: PHAR 10100, PHAR 20100, PHAR30100
• Module leader PHAR20100, PHAR30500, PHAR30600, deputy module leader PHAR10100
• PHAR 30500 BSc projects
• PHAR 30600 Employability and Management

PG teaching

• PIAT: module 71010 (tutor), dissertation board and examination board

Alain Pluen’s research team focuses on:

1. Understanding weak protein protein interactions especially for biopharmaceuticals using fluorescence techniques, light scattering.

In collaboration with Drs Curtis, Warwicker, Golovanov Profs Derrick and Dickson (MIB and FBMH). This work is supported by BBSRC and MedImmune. Aggregation propensity of mABs in simple solutions as well as real formulations has been deternined and compared to standard equipment (Hamrang et al. 2015 JPharm Sci and Shah et al. 2017 Int J Pharm). The effect of charge mutations on teh stability and aggregation of small chain Fv fragments studied (Austerberry et al., Eur J Pharm and Biopharm).

2. Develop the use of Image Correlation Spectroscopies for quantifying :

• peptides uptake in cells (Staley et al., Drug Discovery Today 2010) and to
• protein and biologics aggregation phenomena in collaboration with the Centre of Excellence in Biopharmaceuticals (COEBP).
• We have demonstrated the ability of Raster Image Correlation Spectroscopy at characterising the diffusional behaviour of proteins in solution under normal and stress conditions (Hamrang et al.,J Pharm Sci, 2010): using diffusion coefficients and local concentrations, variations of the particles distribution illustrate the effect of stress on protein solutions. A collaboration with Dr R Curtis (MIB) focuses on te mechanismss of protein aggregation using ManICS and Spatial Intensity Distribution Analysis among other techniques. Another element of this approach is the characterisation of protein aggregation on cells surfaces with Dr P Legembre (Rennes France).

3. Preparation of stable graphene suspensions and their for drug delivery.

4. Understanding the delivery of drugs or biologics 

• Cell penetrating peptides e.g. Tat (Saleh et al., Biopolymers 2008) and amphipathic, DNA-binding cationic peptides e.g. LK15 (Perry et al., J. Fluorescence 2008). This lead to the design of the multifunctional peptide, TatLK15, which successfully mediates cell transfection in cell monolayers and spheroids (Saleh et al., J Controlled Release 2010) andefficiently mediated the silencing of bcr-abl oncoprotein using siRNA and shRNA (Arthanari et al., J controlled Release 2010). We are currently investigating the behaviour of the peptide itself, its pro-apoptotic acitvity and its ability to overcome multidrug resistance. We are currently refining this multifunctional peptide to improve its efficiency in primary cells.

Additionally, in collaboration with Dr Rauch (U. of Nottingham) the influence of phospholipids e.g. phosphatidylserine on drugs uptake in tumour cells is investigated (Rauch and Pluen, Eur J Biophysics 2007) as well as multidrug resistance (Rauch et al., Cellular Biochemistry and Biophysics 2010).

Collaborators

Manchester (UK)

Divivsion of Pharmacy and Optometry

Dr H Aojula

Dr C Demonacos

Dr Richard Bryce

Prof A McBain

Manchester Integrated Biosciences

Nottingham (UK)
Dr C Rauch

National University of Ireland, Maynooth

Dr Jennifer McNamus

• Dr James Austerberry, BBSRC link MedImmune
• Mr Sam Chapman, PhD student, CTP with Croda
• Mr Abdelhamid Eltoukhi, PhD student, peptides delivery.
• Mrs Fai Alkhathiri, PhD student, graphene suspensions
• Ms Maria Grecco, EU ITN Marie Curie PhD student 
• Ms Nicole Sibanda, PhD student, liquid liquid phase separation

Alumni

• Dr Catriona McCallion (former PhD student), currently PDRA MIB Manchester
• Dr Ben Staley (former PhD student) currently working at Actavis.
• Dr Peter Davis (former PDRA with MedImmune) working at Sheffield University
• Dr Myasar Al-kotaji (former PhD student), visiting researcher UCL, Head of Pharmaceutics at Mosul University (Iraq).
• Dr Zahra Hamrang (former PhD student and PDRA) currently working at School of Pharmacy, Strathclyde University.
• Dr Yamini Arthanari (former PGR student) currently working at Astra Zenecca.
• Dr Maryam Shah, (former PGR student), currently working at Proveca Ltd
• Dr Heather Perry. Heather (former PG student, graduated in 2005) currently work for Waters corp.
• Dr Sylvie Lélu: former PGR student and post-doc (2003-2008). Now Post-doc Institute of Physics National Technological University of Norway
• Dr Hayley McGlynn: former PGR student. Currently works as a medical writer.
• Dr Ning Ning former PG  student. Now works at Astra Zenecca.
• Dr Cyril Rauch: former PDRA. Now lecturer School of Veterinary Sciences, U. of Nottingham, UK
• Dr Amer Saleh: former PGR student (2004-2008). currently working at Astra Zenecca.
• Mr Xiaofei Lei (Hank) former Master student. currently undertaking a PhD in Portsmouth

Fluorescence techniques (Zeiss LSM510 Meta Confocor 2):

• confocal laser scanning microscopy cells
• Image correlation spectroscopy i.e. TICS, RICS - Designed our own software (ManICS).
• fluorescence correlation spectroscopy (FCS) in solutions and cells
• fluorescence recovery after photobleaching (FRAP) in solutions, gels, cells

Models:

• cell monolayers (tumours cells)
• tight monolayers (Caco-2, endothelial cells)
• multicellular tumour spheroids
• flow chamber
• composite gels

Peptide synthesis in collaboration with Dr H Aojula

Alain Pluen takes regularly Nuffield placement students during Summer time and is also a school governor of a primary school in the Peak District