University of Warwick
Dr Mike Chappell
Mike's research expertise lies mainly in the modelling and analysis of biomedical, pharmacokinetic and biological processes. Much of the emphasis of this work has been on compartmental modelling and the application of techniques in system dynamics, non- linear systems, control theory and system identification. Mike has particular expertise in structural identifiability analysis, i.e. determining whether the parameters of a postulated model can be estimated if perfect data are available. Such analysis is an important prerequisite for system identification, parameter estimation and experiment design. Over recent years his research has centred on techniques for analysing the structural identifiability of non-linear systems and computer algebra/symbolic computation packages have proved invaluable tools in this context. He also has an interest in the robust simulation of highly stiff systems.
Mike's research has been performed in close collaboration with academic, industrial and hospital-based research groups and funding has been received from a variety of research councils including the EPSRC, the BBSRC and the MRC. He was one of the recipients of the 2001 Snell Premium from the Institute of Electrical Engineers for a paper on wavelet analysis of heart rate variability and its application in the detection of sleep apnoea.
Mike is leader of the Gait (Motion Analysis) Lab, which aims to develop finer scale musculoskeletal models of human motion than are currently used in practise.
James Yates studied pure mathematics at the UoW, graduating in 2000 with a Master of Mathematics degree. He then joined the Electrical Engineering division of the School of Engineering at the UoW where he obtained his PhD. After a short postdoctoral project at Warwick he joined AZ for a 2 year post-doctoral project investigating PK/PD modelling. After that he became a permanent member of staff. He is now a principal scientist in the Innovative Medicines Oncology biotech unit based in Cambridge, UK providing pre-clinical PKPD modelling support of drug discovery and development projects. He is an active researcher in model building methodology, study design and translational PK/PD modelling for oncology and safety.
Teresa graduated in Biochemistry from Sheffield in 2003, then joined AZ in Drug Metabolism and Pharmacokinetics (DMPK) to perform both in vitro and in vivo experiments contributing to the optimisation of DMPK properties of compounds for diabetes targets. In 2009 she was seconded to AZ Sweden performing pharmacokinetic-pharmacodynamic (PKPD) modelling for cardiac arrhythmia projects and on her return she continued supporting diabetes projects with modelling and simulation. In 2012 she joined Safety Pharmacology primarily modelling drug induced cardiovascular effects. Alongside this she studied at Manchester and in 2013 graduated with a MSc in PK/PD Modelling and Simulation. Currently working as a modelling and simulation specialist in the translational safety department she applies model based approaches to the interpretation of in vivo safety data, quantifying the exposure-response relationship and making predictions at therapeutic exposures in human.
Markus Fridén earned his PhD from Uppsala University in 2010, and has since worked at AZ, Mölndal, as PK/PD modeller focusing on experimental and computational methodologies for evaluating targeted drug delivery. Currently Markus holds a co-opted senior lectureship at Uppsala University and heads the DMPK Modelling and Simulation section in the Respiratory, Inflammation and Autoimmunity iMED organization of AZ.
Peter Gennemark, works with mathematical modeling in the area of cardiovascular and metabolic diseases. He holds a PhD in computing science specialising in systems biology.
Joanna Parkinson works at AZ, Sweden as a clinical pharmacometrician. She has worked in AZ for over 5 years and prior to that, she received her PhD in biophysics from Cardiff University, UK and worked as a post-doctorate at Liverpool University. Over the last few years Joanna has been involved in several projects where she worked on PK/PD modelling in cardiovascular safety, efficacy as well as modeling of disease progression.
Swedish University of Agricultural Sciences, Uppsala
Johan Gabrielsson is Professor of Integrative Pharmacology at School of Veterinary Medicine SLU. He has previously worked for almost 20 years within the pharmaceutical industry and was a Senior Principal Scientist at AZ R&D 2002-1012. His responsibilities included kinetic/dynamic related project tasks in the cardio-vascular, gastro-intestinal, central nervous system, oncology & biologics (proteins, peptides and antibodies) areas, in licensing drug projects and was senior consultant to various management teams. He is author of the popular textbooks ‘Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications’ 4th ed. (2nd print 2010) and ‘Quantitative Pharmacology: An Introduction to Pharmacokinetic and Pharmacodynamic Analysis’ 1st ed. (2012). He is also academically affiliated with Department of Pharmaceutics, Univiversity of Tennessee. He has published extensively in the field of PK/PD modelling and reasoning, and has run numerous workshops internally and externally in the area of biological data analysis since 1985 in Europe, the US (FDA) and Asia (>6000 participants) at both the undergraduate and graduate level. His research focuses on modelling different aspects of endogenous turnover, such as functional tolerance and rebound phenomena, physiological limits and target-mediated drug disposition in collaboration with Professor LA Peletier, Leiden University. He has been an external examiner on several PhD theses abroad.
Mats Jirstrand received a MSc degree in applied physics and electrical engineering in 1994 and a PhD degree in automatic control in 1998 both from Linköping University. In 2004 he was appointed associate professor at Chalmers University of Technology. He is the author of over 60 peer-reviewed publications on modelling, simulation, and control systems both for technical and biological applications and has been visiting researcher at the Information Systems Laboratory at Stanford University. Since 2003 he has been at the FCC with responsibility for building a team of highly skilled applied researchers focusing on exploiting the use of mathematics in biological and biomedical applications. Projects are carried out in close cooperation with both academic and industrial partners where pharmacokinetics and pharmacodynamics, arrhythmia, protein synthesis and secretion, kinetic models of metabolic and signaling networks, single cell and medical image analysis, and continuous-discrete identification are applications of particular interest. Examples of software tools developed by his group are Maxsim2, PathwayLab (in collaboration with InNetics), IdentifiabilityAnalysis for Mathematica, Systems Biology Toolbox for Matlab, and CellStat.
Early Stage Researchers
I received my MSc and MSE in Engineering Mathematics and Computational Science at Chalmers University of Technology in 2013. The programme is designed to provide a solid base in mathematics, mathematical statistics, and computational science. It also provides the opportunity for students to profile themselves as biomathematicians or biostatisticians, a path that I undertook. By taking courses in systems biology, bioinformatics, and population genetics, I nourished my interest in Life Sciences. I have always been motivated by making a difference and improving the quality of life of others, and this is what made me apply for the IMPACT project.
My project is about dose-response-time data analysis, a PD modelling technique applied mainly in preclinical studies when PK data are sparse or lacking. This is typically the case with pulmonary or epicutaneous drug administration. The idea is to postulate a kinetic model describing the dynamics of an intermediate biophase where the drug’s pharmacological effect take place. This is done by extracting kinetic information solely from PD response data. Hopefully this will increase the understanding of the drug behaviour, simplifying decision making in future drug development. Although the project has its focus on dose-response relations, the technique can be generalized to any biomarker problem where an input and output is known but an intermediate step is unobserved.
Currently, I am working on a dose-response-time data analysis on nicotinic acid-induced differences in free fatty acid levels in the blood. The study is conducted with a very rich data set with several different provocations and administration routes, and the data show some interesting features e.g. feedback, rebound and tolerance build-up. The behaviour of this system is captured by a semi-mechanistic model based on turnover equations in combination with control theory techniques to explain the tolerance build-up. The idea is to investigate different biophase models and to apply a PD model that describe the data well, all in a structurally identifiable framework.
Beside my research project, I also get a kick out of running, choral singing, reading, and attending concerts (all kinds of music).
I received my MSc in Engineering Biology, Linköping University, Sweden in January 2013. This interdisciplinary five year programme provided me with a wide range of courses in fields such as mathematics, control theory, programming, systems biology, biochemistry and physiology. I was happy to spend my fourth year as an exchange student at Queensland University of Technology, Brisbane, Australia.
During my studies, I worked with Professor Peter Strålfors and Dr Gunnar Cedersund at Linköping University, where we developed models describing the dynamics of intra-cellular insulin signalling in primary adipocytes. My MSc project was focused on developing mathematical models to predict insulin need for type 1 diabetics.
After my graduation I moved to Cambridge, US for a trainee position at Merrimack Pharmaceuticals. Here, I worked with a mathematical model of the cellular DNA damage response pathway together with Dr Ozan Alkan. After finishing this internship, I started my PhD programme at UoW, which is further presented in the results section of this website. My PhD was awarded in February 2017 for my thesis entitled ‘Predicting QRS and PR Interval Prolongations in Humans using Nonclinical Data’.
I studied the pharmacy programme at the University of Gothenburg and did my master’s thesis at AZ, focusing on tracer identification for an in vivo target occupancy methodology. After the completion this project, I have mainly worked with modelling and simulation of preclinical PK/PD data in the pharmaceutical industry.
Despite the historical success of inhalation medicines, there is very little known about the fundamental prerequisites for a drug molecule to be retained in and exert a localized effect in the lung when administered by inhalation. My PhD project evaluated the lung tissue target exposure to unbound drug in the lung after inhalation, both by using different experimental methodologies and mathematical modelling. In October 2016 I was awarded my PhD for my thesis entitled 'Lung-Targeted Receptor Occupancy by Drug Inhalation: An Experimental and Computational Evaluation'.
I received my MSc in 2012 from Linköping University, Sweden, in Engineering Biology. The programme is very interdisciplinary ranging from organic chemistry, biochemistry, immunology and physiology to more classic engineering fields such as computer science, physics, mathematics and control theory. The overall aim of this program was to build a basis for implementing well established engineering approaches in biology.
Before starting my PhD studies at University of Warwick I’ve been part of a couple of modelling projects. In parallel to my undergraduate studies I was involved in teaching in a systems biology course for two years. In my Master’s thesis I studied cell-to-cell variation using nonlinear mixed-effect modelling. I continued this work as a research engineer at Linköping University after I finished my MSc.
As a research engineer I also used nonlinear mixed-effect modelling in a non-invasive liver biopsy project. In that project, I used time-resolved data from MRI-scans of the flow of contrast agents between different compartments in the liver in order to estimate patient specific parameters as a part of a liver diagnostic framework. During this time, I was a part of Gunnar Cedersunds ISB-group at Linköping University.
In January 2013 I started an internship in Cambridge, MA, USA, at Merrimack Pharmaceuticals. There, I used PKPD-modelling in a late stage pre-clinical cancer drug development project working closely with experimentalists. In particular, I worked with predicting efficacy and toxicity of a drug experimental design of studies of preclinical species.
My PhD project at University of Warwick addresses the issue of structural identifiability in QSP. Structural identifiability concerns whether given a certain model structure, the parameters in the model can be uniquely (locally/globally) determined using perfect input/output signals. If this is not the case, the model predictions are not reliable since any arbitrary value on the model parameters can describe the data. From this point, one could either (i) reformulate the model or (ii) suggest new experiments which would make the model parameters structurally identifiable.
I graduated from Lund University in 2006, with a Master of Science degree in Engineering Physics.
I did my master’s thesis in the Division of Atomic Physics, carrying out measurements on prospective quantum computing hardware. After graduation, I have mainly been working with digital signal processing for communications systems