Research Supervisor Details

This page provides additional information about our research supervisors to help you choose an appropriate supervisor. You can either browser supervisors by school or search for them. Most supervisors also have a personal webpage where you can find out more about them. If that is not listed here you can also try searching our main pages: search our site

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Professor Ingunn Holen
i.holen@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

My main research interest is understanding how cancer spreads to the skeleton, in order to identify new therapeutic approaches that will prevent this from happening. Around 80% of patients with advanced breast and prostate cancer will experience that their cancer spreads to the skeleton, resulting in pain, weakening of the bone and sometimes fractures. At this stage the cancer is incurable, with patients living an average of 2 years. In order to improve patient outcome we need to understand the cellular and molecular mechanisms that underpin cancer progression in bone, which is the focus of my research.

The research in my team is focussed on tumour cell dissemination in bone, and how this is influenced by the microenvironment in breast and prostate cancer. We use cutting edge technology to study the early stages of bone metastasis and how single cancer cells may remain dormant or start to proliferate when encountering different environments. We work to elucidate the molecular mechanisms involved in tumour cell-bone cell interactions, and how these can be targeted by anti-cancer therapies, including CDK4/6 inhibitors. We also investigate the role of the microenvironment in driving progression of bone metastases, the effects of female hormones, and how therapeutic agents affect the bone and tumour vasculature.

I have several collaborative projects both with other researchers in the medical school, nationally and internationally. I work closely with my clinical colleagues on translational research projects, transferring the results from our laboratory projects into clinical feasibility studies.

Students will be part of a enthusiastic team of post docs, technicians and clinical fellows that all work on related projects, have the opportunity to use a range of techniques and to present their work at workshops and conferences.

Professor Janet Brown
j.e.brown@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

As a clinician scientist, I engage in both clinical and laboratory research, which is internationally recognised, with publications in Lancet, Journal of Clinical Oncology, Journal of the National Cancer Institute, Nature Clinical Oncology, Clinical Cancer Research, Annals of Oncology Breast Cancer Research and Treatment and other journals. I lead the Clinical Bone Oncology and Biomarkers Group in University of Sheffield (LINK), which has a particular focus on the impact of cancer on the skeleton in patients with breast, prostate and renal cancer. Our recent research includes the use of biomarkers in established bone metastasis to aid patient management and studies of the negative impact of cancer treatments on bone health. One of the main objectives of our current clinical and laboratory work is to develop novel prognostic and predictive biomarkers for clinical use in patients with early cancer to help in prevention or delay of cancer metastasis to bone, after which disease is incurable.

I also run clinical studies to develop innovative therapeutic approaches in breast, renal and prostate cancer. As Chief Investigator, I currently lead a large UK-wide, 40 centre, clinical trial (STAR) funded by NIHR, to determine whether treatment breaks in patients with renal cancer receiving targeted therapies, can reduce toxicity and have health economic benefits, without loss in efficacy. I am also PI on a clinical study funded by Cancer Research UK aimed at evaluating a potentially exciting new form of virotherapy in patients with prostate cancer.

Dr Jane Fearnside
j.fearnside@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

My research interests are investigating the long-term consequences of cancer treatment.

Professor Lynda Wyld
l.wyld@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

Tumour microenvironment and the unfolded protein response, breast cancer in the elderly, psych-oncology, familial breast cancer, breast screening.

Professor Sarah Danson
s.danson@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

My clinical and research interests are in melanoma and lung cancer. My background is in the early clinical assessment of new anticancer agents. Sheffield is an `Experimental Cancer Medicine Centre´ and its aims are to expand the early clinical trial portfolio and produce associated translational work. I am ECMC Lead elect and I also sit on the Cancer Research UK New Agents committee, which complements this.

Melanoma is on the increase and this is not all due to excess sun exposure. I chair the Sheffield Melanoma Research Group which has obtained collaborative grants. Funding was obtained from Weston Park Hospital Cancer Charity to look for epidemiology and biological features of cutaneous melanoma (principal investigators: Dr Sarah Danson, Dr Angela Cox, Dr Dawn Teare, Dr Kevin Walters, Dr Andrew McDonagh, Dr David Hughes). 87 patients were enrolled into the GEMS study (Genetics and Epidemiology of Melanoma in Sheffield). Translational work on the samples is complete and the manuscript is being written. The WPH Cancer Charity has also funded a grant to identify novel genes regulating the development of uveal melanoma metastases (principal investigators: Dr Karen Sisley, Dr Sarah Danson, Professor Ian Rennie). We enrol patients into clinical trials for melanoma if at all possible. I am Chair of the Rare Tumour Group, which aims to increase trial activity in less common cancers such as melanoma. Recent studies include agents targeting VEGF (AVAST-M), MEK inhibitors (PACMEL and COLUMBUS). AVAST-M and RADVAN recently completed accrual and the interim results of AVAST-M have been published in the Lancet Oncology.

Dr Stephen Bradley
stephen.bradley@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

I am a GP with an interest in diagnosis, particularly cancer diagnosis, in general practice. My work has predominantly focused on lung cancer.

Dr Andrew Chantry
a.d.chantry@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

His principal research interests are anabolic strategies in the treatment of myeloma bone disease and novel strategies to target myeloma tumour. He also has holistic research interests including life with cancer – holistic care and quality of life studies, computational modeling of cancer including using digital simulations and game technology.

Professor Syed Hussain
syed.hussain@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

My major areas of interest are management of urological cancers, clinical trials, early drug development and translational medicine. I have set up a large number of clinical trials from early phase to late phase studies during my career. My work on organ preservation in bladder cancer moved all the way from an early phase I study (Hussain et al Annals of Oncology 2001), to phase II efficacy study (Hussain et al BJC 2004) that led to a Cancer Research UK funded study BC2001 trial that was reported in New England Journal of Medicine (James, Hussain, Hall et al April 2012). This study has now changed the standard of care for patients with muscle invasive bladder cancer opting for organ preservation treatment.

Dr Stuart Hunt
s.hunt@sheffield.ac.uk
Personal Webpage

School of Clinical Dentistry

Research interests

Head and neck cancer (HNC) is the 8th most common cancer in the UK. There are approximately 12,400 new HNC cases diagnosed in the UK each year and over 4,000 HNC-related deaths annually (Cancer Research UK). The Hunt Lab focuses on the role of extracellular vesicles (and other extracellular particles) in HNC. We research the mechanisms regulating their production (biogenesis) and how they mediate intercellular communication within the tumour microenvironment. We also explore how they could be exploited as a source of diagnostic/prognostic biomarkers and as novel therapeutic targets for head and neck cancer. Working in a clinical department, we have access to ex vivo patient samples and a wide range of HNC cell lines for in vitro studies.


Professor Ali Khurram
s.a.khurram@sheffield.ac.uk
Personal Webpage

School of Clinical Dentistry

Research interests

 

I am a Professor and Honorary Consultant in Oral and Maxillofacial Pathology. Prior to that, I worked as a Senior Clinical Lecturer (2016-2022) and as a NIHR Academic Clinical Lecturer/ Honorary Specialist Registrar (2011-2016) at the University of Sheffield.

I have a strong interest and am actively involved in research and teaching (undergraduate, postgraduate, clinical) as well as diagnostic oral, maxillofacial and head and neck pathology. I am the founder and Lead of the NEOPATH Research Group working with a team of researchers and clinicians on various aspects of head and neck cancer diagnosis and prognosis prediction. In addition to local research projects, my group is working with a wide range of collaborators and funders across the world.

I am passionate about raising the profile of Pathology as a specialty and raising awareness of head and neck cancers. I work closely with a number of patient groups and charities and am a Trustee and Patron for The Swallows Head and Neck Cancer Charity.

 

 

Professor Angela Tod
a.tod@sheffield.ac.uk

School of Allied Health Professions, Nursing and Midwifery
Research Interests

My research has mainly focused on care for adults and older people. My particular research focus is on patient experience studies, especially in areas of public health, health inequalities and health care access. Recent work  includes a growing portfolio of older people’s research, specifically mesothelioma and lung cancer. I am currently co-director of the Mesothelioma UK Research Centre 

 

Research methods
Qualitative methods 
Mixed methods studies
Professor Penelope Ottewell
p.d.ottewell@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

My research is focused on advanced breast and prostate cancer with particular emphasis on bone metastases. Primarily, this involves using a complement of in vitro and in vivo model systems to investigate the molecular alterations responsible for metastases to bone and response to treatment. Metastases are a result of a stepwise accumulation of genetic/epi-genetic mutations promoting distinct molecular alterations that drive different stages in the metastatic process; mutations involved in intravasation are not the same as those involved in tissue homing and colonisation. Importantly, molecular alterations acquired by tumour cells have profound effects on cytokine production and immune cell regulation. My research team hypothesise that cytokine driven changes to the tumour immune environment promotes metastatic spread and that pharmacological regulation of immunity may provide effective treatment methods for, currently incurable, bone metastasis. The aims of my research are to: (A) Identify specific molecular and immune cell regulatory determinants involved in tumour cell intravasation, homing to bone and colonisation of the metastatic site. (B) Decipher how these determinants impact on treatment efficacy in different cancer subtypes. (C) Establish more effective treatments for metastatic breast and prostate cancers.

Dr Karen Sisley
k.sisley@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

My research interests are the genetic and biological behaviour of uveal melanoma.  Initial studies have lead to a good understanding of some of the principle genetic changes in uveal melanoma and how they correlate and can be used to predict prognosis.  My research continues to investigate the genetic basis of uveal melanomas but has broadened in recent years to consider how the interaction with the environment affects the way these melanomas develop.  In addition I have become actively involved in investigating the genetic characterization of sarcoma and developing a molecular pathological classification suitable for all subtypes.

Professor Alison Gartland
a.gartland@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research interests

My research group is interested in how our bones function in health and disease with an emphasis on cancer. We are interested in knowing why primary bone cancers occur and how to best treat them. We are also interested in trying to understand why and how primary cancers such as breast and prostate spread preferentially to bone. Other interests include investigating mechanisms leading to osteoarthritis and failure of orthopedic implants. We use cutting edge scientific techniques and technologies, both in vitro and in vivo,  to answer clinically relevant questions.   

Dr Lynne Bingle
l.bingle@sheffield.ac.uk
Personal Webpage

School of Clinical Dentistry

Research interests

My long-standing research interests have been focused on the role and regulation of epithelial secretory proteins. This work has principally involved the study of the airway epithelium, through the use of 3D in vitro model systems, but more recently has expanded to include the oral and nasal mucosa and the epithelium of the middle ear. My specific interests have focused on the fields of innate immunity, host defence and tumour biology.

I have also recently started to investigate the potential of using my tissue culture expertise to develop in vitro models of human salivary glands from fresh human tissue. We are now routinely isolating cells from human sublingual glands and are currently characterising cell phenotype under different culture conditions. The mid-term aim is to use these models to begin to elucidate the initial stages of salivary gland diseases such as Sjogren’s syndrome and salivary gland tumours.

 

 

Professor Daniel Lambert
D.W.Lambert@sheffield.ac.uk
Personal Webpage

School of Clinical Dentistry

Research interests

The interests of our research group fall in three broad interlinking areas, all of which seek to identify novel opportunities to improve quality of life.

Molecular mechanisms of cell:cell communication in ageing and cancer 

The behaviour of all cells is dictated by the signals derived from the surrounding microenvironment. In ageing and cancer, these signals may become corrupted by changes in surrounding cells, or by biomechanical or chemical changes to the extracellular matrix (ECM). A major focus of our work is to identify the mechanisms by which these signals, become corrupted. We are particularly interested in the role of signals derived from senescent cells, particularly the major cell type of connective tissue, fibroblasts, which accumulate with age and in several diseases, including cancer.  These signals include proteins, RNA (particularly non-coding RNA), DNA and extracellular vesicles.

Spatial analysis of the tissue microenviroment

In order to understand the mechanisms outlined above, we need to better understand the changes that happen within tissue in ageing and cancer. We are applying cutting edge spatial 'omics' techniques to understand, at an unprecedented level of resolution, the changes occuring in the phenotype of cells in aged and diseased tissue.  This will allow us to much more accurately model changes in the tissue microenvironment and identify potential new, individualised, therapeutic opportunities. We are also working closely with biomaterials scientists to use this information to use materials to mimic the tissue microenvironment, allowing us to accurately model the processes occuring in the body and also develop new ways to reverse disease-associated changes and regenerate damaged tissue.

Biomarker discovery 

The diagnosis and monitoring of many diseases, including cancer, requires painful collection of tissue. We are working closely with world-leading physical scientists to develop new ways to detect 'biomarkers' of cancer in blood and saliva, allowing non-invasive or entirely painless disease diagnosis and monitoring. These approaches include nanoplasmonics and other methods not routinely used for biological applications, but with the promise to revolutionalise disease sensing. We are also applying these technologies to the analysis of senescence, to allow accurate determination of biological age and support the development of drugs designed to reduce the health impacts of ageing.

 

 

Mr Ben Kearns
b.kearns@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research interests

  • The use of statistics in health economics
  • Extrapolation and time-series analyses
  • Survival analysis and model uncertainty
  • Vascular disease, cancer, depression
  • Chronic diseases, mental ill health, and their interactions
  • The use of health economics for pathway (service) re-design
  • Mathematical modelling, including simulation
Dr Michelle Lawson
m.a.lawson@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

My main research interests are myeloma-induced bone disease and dormant tumour cells. Over the last 12 years I have developed and established several preclinical murine models of myeloma to study therapeutic agents in the early, mid and late stages of the disease. This has led to an increased understanding of the role of the bone microenvironment and how it influences tumour growth. I am currently investigating the use of bisphosphonates in combination with other bone modulating agents to repair myeloma-induced bone disease and using novel agents to target dormant myeloma cells in the bone marrow, with the aim of translating these findings into patients.

Dr Catriona Mayland
c.r.mayland@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

My research interests are focused on palliative and end-of-life care. In particular, I am interested in conducting research in the following areas:

  • Integration of palliative care – within routine oncological care and within primary care
  • Head and neck cancer
  • Assessment of quality of care for dying patients
  • Engagement of bereaved relatives within research
  • Development, validation and use of outcome measures

I am currently undertaking a Yorkshire Cancer Research (YCR) Senior Clinical Research Fellowship. My post-doctoral work has focused on the development, validation and use of outcome measures to evaluate the quality of care in the last days of life, as perceived by bereaved relatives. My tool, ‘Care Of the Dying Evaluation’ (CODE), is a post-bereavement questionnaire which has been used on an international basis to help identify and improve aspects of clinical care. Additionally, I have developed work on improving palliative care for specific complex groups, such as those with head and neck cancer. I use both qualitative and quantitative research methodologies.

Dr Sophie Whyte
Sophie.Whyte@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

My broad research is focused on mathematical modelling within health economics. I have gained significant expertise and experience in two related areas:

  • Bayesian calibration of cancer natural history models: This is my main methodological research theme, please see MDM publication http://mdm.sagepub.com/content/31/4/625 and Example Excel model using the Metropolis Hastings algorithm to calibrate a state transition model available to down load from the Downloads box)
  • Early diagnosis of cancer: I have substantial experience having worked on more than 15 projects in this area of applied research.
  • In addition to these main research themes I have undertaken research to inform policy making: Health Technology Assessment (HTA) for NICE (https://www.shef.ac.uk/scharr/sections/heds/collaborations/tag) , and research as part of the Policy Research Unit in Economic Evaluation of Health and Care Interventions (EEPRU) for DH (http://www.eepru.org.uk/)
Professor Spencer Collis
s.collis@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research interests

The overarching research goal of the Collis laboratory is to identify and functionally characterise novel factors that are important for the maintenance of genome integrity in human cells. This research also aims to establish if such factors are novel drug targets and/or biomarkers that can be exploited to improve the treatment of diseases such as cancer, either alone, or in combination with existing chemo- and/or radio-therapeutic regimes. To achieve this, the Collis group collaborates with a range of national and international scientists and clinicians to maximise the potential therapeutic impact of their basic biological discoveries.

Dr Vanessa Hearnden
v.hearnden@sheffield.ac.uk
Personal Webpage

School of Chemical, Materials and Biological Engineering

Vanessa’s research focuses on tissue engineering as a tool to both understand the fundamentals of disease processes and to develop novel diagnostic and treatment strategies.

Tissue engineering of soft tissues for the treatment of disease

Vanessa is interested in developing tissue engineered products and biomaterials for the treatment of disease or injury, in particular those affecting the oral mucosa. She has a strong interest in clinical translation and has a network of clinical collaborators.

Three dimensional in vitro models of oral cancer

Vanessa, along with colleagues in the School of Clinical Dentistry, developed a series of tissue engineered models ranging from healthy oral epithelium to precancerous dysplastic lesions and invasive squamous cell carcinoma. These three dimensional in vitro models provide a valuable tool for studying many aspects of tumour biology  as well as novel diagnostic and therapeutic technologies.

Fat derived cells for soft tissue wound healing

It is well known adipose tissue contains large quantities of mesenchymal stems cells but how best do we isolate, process and utilise these cells from fat to heal soft tissue wounds?

Dr Iwan Evans
i.r.evans@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Lay summary
Immune cells play an important role in the normal development, general upkeep and repair of our bodies, in addition to their roles defending against infection and disease.  An important function of a subset of our white blood cells (called macrophages) is to detect, ingest (phagocytose) and degrade debris, dying cells and invading pathogens. When these processes go wrong it can cause or worsen a wide range of human diseases and conditions including autoimmunity, atherosclerosis, cancer and chronic inflammation, often due to the inappropriate behaviour of the macrophages themselves.

A major problem is that we do not fully understand how the function of macrophages is controlled; understanding this would enable the generation of therapies aimed at manipulating macrophage behaviour and so prevent or reduce their contribution to these damaging conditions.

Fruit flies (Drosophila) are considerably simpler than vertebrates such as ourselves, yet the key genes important in macrophage function are also present.  This makes it much easier for us to study and identify new genes involved in macrophage functions such as migration, phagocytosis and degradation of ingested material. Importantly fruit flies contain a population of cells called hemocytes that are very similar in their function and behaviour to our own macrophages.

Contact with cells undergoing a programmed form of death (called apoptosis), which often occurs at sites of injury or pathology, is thought to alter the behaviour of macrophages.  This can be helpful in some circumstances but on other occasions it may cause macrophages to contribute to disease progression. Drosophila hemocytes display altered responses when challenged in the presence of increased levels of cell death. Therefore we are using this system to try to understand how apoptotic cells regulate macrophage function.

Technical summary
Drosophila hemocytes are a population of highly migratory macrophages that disperse over the entire embryo during development. They represent the cellular arm of the innate immune system and clear both apoptotic cells and pathogens - without these functions development or survival in the face of infection are strongly perturbed, respectively.

The unparalleled imaging capabilities of hemocytes within the developing embryo, coupled with the well-established and rapid genetics of Drosophila, enable the cell biology underlying macrophage function to be determined in the context of an intact organism.

Clearance of apoptotic cells is crucial for development and this process is known to alter macrophage function.  Undigested apoptotic corpses within hemocytes can suppress both their general motility and inflammatory responses.  Using this model system we are studying how apoptotic corpses affect macrophage behaviour at a number of stages during the process of apoptotic cell clearance.  We are particularly focused on how the stages post-engulfment can inhibit the migratory machinery of hemocytes. This mechanism could have important consequences for a wide range of human diseases, since it could contribute to the inappropriate or prolonged localisation of macrophages at the numerous sites of pathology that contain high levels of cells dying by apoptosis.

 

Lab webpage - http://iwanrevans.weebly.com/

Professor Fiona Boissonade
f.boissonade@sheffield.ac.uk
Personal Webpage

School of Clinical Dentistry

Research interests

I have a major research interest in the mechanisms of altered neuronal excitability that occur under the pathological conditions of nerve injury and inflammation, and which contribute to the development of chronic pain, including that in the oro–facial region. Much of this research has been done at the academic–industrial interface. Collaborations with GSK, Pfizer and Eli Lilly have funded a wide range of pre-clinical translational studies, using pre-clinical models and human tissues to identify and validate a range of regulators of neuronal excitability as potential targets for the development of novel analgesics and anti-inflammatory mediators.

Other research projects are directed towards improvement of nerve regeneration. This work investigates methods of improving nerve repair through the use of a range of anti-inflammatory and anti-scarring agents, and includes collaboration with the Department of Engineering Materials at the University of Sheffield to develop bioengineered conduits to enhance nerve regeneration. In other projects I collaborate with the Sheffield Institute for Translational Neuroscience (SITraN) investigating the role of chemokines in CNS disease.
I also have a significant research interest in neural–immune interactions and their role in the development of disease. I have a number of pilot projects underway in this field investigating neural interactions in the generation of cancer pain and tumour progression.

 

 

Professor Alexander Fletcher
A.G.Fletcher@sheffield.ac.uk
Personal Webpage

School of Mathematical and Physical Sciences

I am a mathematical biologist. I develop and apply mathematical and computational models to study the growth and dynamics of tissues in embryonic development and in disease.  I use a variety of modelling approaches to address questions in this area, from compartment models to individual cell-based and multiscale models, often in close collaboration with experimental biologists.

Professor Craig Murdoch
c.murdoch@sheffield.ac.uk
Personal Webpage

School of Clinical Dentistry

Research interests

Main interests are centred on oral epithelial biology, the mechanisms of oral disease pathogenesis and development of new treatment strategies. I am particularly interested in how immune cells are recruited to and act at diseased oral sites and how they interact with other cells/microbes within the local microenvironment. My group has developed novel tissue engineered in vitro models of both healthy and diseased oral mucosa (and skin) to investigate disease processes. I have a long-standing track record of utilising these in vitro 3D engineered tissues as well as zebrafish larvae as direct replacements for animal models and have used these to study the role of oral microorganisms in mucosal and systemic disease. I’m also involved in projects aimed at fabricating oral patches and microneedles made from mucoadhesive polymers for oral mucosal drug delivery. Here we have produced electrospun patches to deliver small molecule drugs such as glucocorticoids, analgesics, antifungals and larger molecules such as antibodies and mRNA for vaccine delivery. I also work within a consortium of researchers developing electrical impedance as a form of non-invasive early diagnostics for the detection and management of oral premalignant disorders.

Current projects include:

  • Novel forms of oral mucoadhesive drug and vaccine delivery and the role of xenobiotic metabolising enzymes in the oral mucosa.
  • Development of tissue engineered oral mucosal and skin model - atopic dermatitis, oral lichen planus
  • Host-pathogen interactions at the mucosal surface.
  • Role of innate immune cells in head and neck cancer.
  • Use of zebrafish to examine the role of oral microbes in systemic disease.
Dr Zeyneb Kurt
z.kurt@sheffield.ac.uk
Personal Webpage

School of Information, Journalism and Communication

Research Applications

My research interests cover use of data science and machine learning models to address problems in bio-informatics, computational biology and health-informatics fields. For example, I develop new or employ established data science and machine learning models to understand the key mechanisms underlying diseases by integrating multi-omics data resources. I also have an interest in employing explainable AI to predict the subtypes of different cancer types from the pathological images; predicting the associations between circular RNA, microRNA, and target genes which drive a particular type of cancer.

Example topics:

-Prediction of biomarkers (e.g. circRNA, microRNA or mRNA) and their interactions for a given cancer type.

-Integrating multi-omics data resources for biomarker prediction in common human diseases such as cardiometabolic disorders.

-Using explainable AI to analyse histopathological images to predict subtypes within a cancer cohort and extending this approach to other cancer types.

Dr Cyril Sanders
c.m.sanders@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

Replication and gene regulation in papillomavirus.
Structure and function of helicases and replication/transcription control proteins.
DNA helicases involved in the DNA damage response and their potential as therapeutic targets in cancer.

Professor Paul Tappenden
p.tappenden@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research interests

  • Applied health economic modelling

  • Model structuring methods

  • Economic analyses of cancer therapies, including survival analysis

  • Whole disease modelling

  • Modelling methods development

Professor James Chilcott
j.b.chilcott@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

* Modelling in public health

* Modelling in cancer and cancer screening

* Methodological modelling interests including:

  • the modelling process and errors in HTA models
  • cognitive mapping for systematic reviews in complex settings
  • structural uncertainty in models
  • Bayesian analysis of joint disease natural history and test characteristics in screening
  • value of information methods
  • probabilistic sensitivity analysis methods
  • meta modelling
  • information gathering processes for models
Professor Claire Lewis
claire.lewis@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

Our research is focused mainly on the role of inflammatory cells called macrophages in tumour progression and tumour responses to conventional anti-cancer treatments like chemotherapy and irradiation. We have also developed ways of using these cells to target therapeutic genes and viruses to tumours. Our work was reported in the national presshttp://www.bbc.co.uk/news/health-20795977, and is mainly funded by grants from Cancer Research UK.

Professor Sherif El-Khamisy
S.El-Khamisy@sheffield.ac.uk
Personal Webpage

School of Biosciences

Research Interests:

Mammalian genome stability in health and disease. I head the human DNA repair group aiming to understand how defects in repairing DNA damage cause degenerative disorders and cancer. Our lab is primarily funded by fellowships from the Wellcome Trust and the Lister Institute of Preventive Medicine.

Dr Carolyn Staton
c.a.staton@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

My research focus is on the regulation of angiogenesis, the development of new blood vessels from the pre-existing vasculature, in wound healing and tumour development and progression. Angiogenesis and haemostasis, the coagulation cascade leading to clot formation, are among the most consistent host responses associated with cancer. Many haemostatic proteins stimulate angiogenesis by up-regulating the expression of vascular endothelial growth factor (VEGF) and its receptors on endothelial cells. Other haemostatic proteins act directly on endothelial cells to inhibit or stimulate angiogenesis. Moreover, recently proteins originally identified as important in neuronal guidance are now suspected to be involved in regulating angiogenesis, both positively and negatively. Thus a comprehensive understanding of the relationships between these important processes under normal conditions (such as wound healing) and in the manner in which this changes during development and progression of cancer has implications for cancer therapy. Collaborative research with colleagues in Sheffield also includes investigating the effects of HDACi on the expression of these and other angiogenesis related proteins in cancer, and the potential anti-angiogenic effects of the ADAMTS family.

Dr Kai Erdmann
K.Erdmann@sheffield.ac.uk
Personal Webpage

School of Biosciences

Research interests

Membrane trafficking and signalling in polarised cells. Role of multi-PDZ domain proteins in cancer formation, metastasis and tumor invasion.
Our group is interested in the regulation of membrane trafficking and its relation to human diseases. In particular we are interested in the molecular mechanism leading to Lowe syndrome, a X-linked disease characterized by congenital cataracts, mental retardation and kidney failure. Moreover, we analyze the molecular function of multi-PDZ domain proteins (PTPN13 and FRMPD2) in vesicular trafficking and signal transduction as well as their role in cancer development and progression.

Professor Munitta Muthana
m.muthana@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research interests

My research focuses on the role of innate immune cells like macrophages and dendritic cells in diseases including cancer and rheumatoid arthritis.  Recently, I have used my knowledge of this area to develop innovative cell-based methods to target anticancer thereapy to tumours.  For example, I have devised a way to use macrophages to deliver large quantities of cancer-killing virus to both primary and secondary tumours simultaneously (click here).  My group is also interested in improving the delivery of therapies to diseased tissue using a nanomagnetic targeting approach.

Dr Paul Taylor
P.M.Taylor@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

My research interests include prognostication and clinical decision-making, particularly with respect to end of life care.  In addition to developing my own ambitions, I have worked with St Luke’s on their existing research portfolio, including EnComPaSS and project ECHO. 

I have collaborated with researchers nationally to support St Luke’s involvement with the £1.3m Yorkshire Cancer Research funded RESOLVE study, and the NIHR portfolio StOIC study, exploring management of opioid-induced constipation in cancer patients.

In collaboration with colleagues at ScHARR, I am undertaking research into Avoiding Emergency Admissions in Palliative Patients, funded by the Sheffield Health Care Challenges Collaboration.

Dr Helen Matthews
h.k.matthews@sheffield.ac.uk
Personal Webpage

School of Biosciences

Our research group is focussed on understanding how cells divide in normal tissues and during cancer development and metastasis. To do this we take a multidisciplinary approach, combining imaging and cell biology with biophysical techniques to measure mechanical forces associated with cell division.

Cell shape and mechanics during cell division

Cells go through a series of dynamic shape changes when they divide. These include cell rounding and stiffening in early mitosis and separation into two daughter cells at cytokinesis. We want to understand how these changes are co-ordinated by dynamic regulation of the actin cytoskeleton throughout cell division. We are particularly interested in how cells divide within epithelial tissues where they must maintain attachment with neighbouring cells to preserve tissue integrity and organisation.

Cell division in cancer

Cancer is a disease of uncontrolled cell proliferation and division. We are investigating how genetic mutations in cancer cells affect the cell division process. In recent work, we found that Ras oncogenes change cell shape and mechanics during mitosis (Matthews et al. 2020). We are now exploring how changes to cell division induced by the oncogenic kRas promote the formation of tumours during the early stages of pancreatic cancer development.

We are also interested in how the modified micro-environment within a tumour affects cancer cell division. Tumours are usually far stiffer than healthy tissue due to cell crowding and the deposition of extra-cellular matrix. We use micro-fabrication techniques to mimic some of the mechanical stresses (eg. compression, stretch) found in tumours to study how these conditions impact cell division.

Professor Helen Bryant
h.bryant@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

A key stage in cell division is the copying of DNA (DNA replication). The proteins involved in replication (the replication complex) move along DNA copying it, however, if they come across a section of DNA that is damaged, replication stops. At this point multiple proteins are activated, they serve to stabilise the replication complex and help by-pass or correct the problem. If the damage is too great to repair, normal cells have a self-destruct mechanism called apoptosis. Through repair and apoptosis normal cells ensure that damage in DNA is not passed to their daughter cells, this is important as damage can lead to dysfunction of the proteins encoded in that section of DNA and thus to cellular dysfunction and disease.

In cancer cells there can be defects in the repair and apoptosis pathways which cause inaccurate copying of DNA and further contribute to the cancer. Chemotherapy causes massive damage to DNA at the point of cell division, in this way in dividing cells it triggers cell death (hence the tumour dies and we see side effects in normal tissue). Some cancers can also become resistant to chemotherapy as they no longer have a functional self-destruct mechanism. In these cases the tumour continues to grow with increasing amounts of damage being passed onto the new tumour cells.

The aim of my research is to understand what happens in a cell when DNA replication is slowed or stopped by damage in DNA. I want to understand which proteins bind to the arrested DNA, whether they are modified in any way and what significance this has on the reestablishment of replication.
By understanding the normal control mechanisms in cells I aim to understand why defects in the proteins involved are associated with cancer. I want to pinpoint differences between dividing tumour cells and dividing normal cells and determine which are important in cancer development. This will enable us to develop drugs which can specifically kill the tumour cells rather than just all dividing cells.

We have particular interests in the mechanisms of genetic instability in bladder, breast and uveal cancer and enjoy close ties with our clinical colleagues in the Royal Hallamshire Hospital (including several joint projects). This enables us to translate our research quickly into potential therapies.

Dr Kyra Campbell
kyra.campbell@sheffield.ac.uk
Personal Webpage

School of Biosciences

In many cancers cells acquire abnormal motility behaviour leading to metastasis, the main cause of cancer related deaths. It is now clear that processes normally driving the tightly controlled movement of cells during development, are reactivated in metastatic cancers in a non-regulated manner.

These processes are called the epithelial-to-mesenchymal transition (EMT) and the reverse mesenchymal-epithelial-transition (MET), and they enable cells to reversibly switch between stationary and migratory cell states. While many signals capable of inducing cells to undergo an EMT have been identified, about MET very little is known, and the molecular mechanisms orchestrating both processes remain poorly understood. We use the model organism of the fruit fly Drosophila melanogaster to study the basic biology of these processes during normal development and also during tumour progression in exciting new Drosophila cancer models that we have recently generated.

Professor James Catto
j.catto@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

James currently runs a lab in the Academic Unit of Molecular Oncology, encompassing 2 post-docs, 2 technicians, 3 Phd students and 1 ACF.  They research the translational application of molecular biology to urological malignancies, and in particular Bladder and Prostate Cancer.  James's particular interest is in the epigenetic alterations seen within these tumours.

Dr Vincent Cunliffe
v.t.cunliffe@sheffield.ac.uk
Personal Webpage

School of Biosciences

Research Interests

Our research is focused primarily on understanding the roles of chromatin regulatory proteins in the development of the zebrafish Central Nervous System (CNS) and in diseases such as cancer. In addition, we are exploiting the technical advantages of the zebrafish embryo to investigate the functions of other genes previously implicated in human neurological disorders. A third area of interest is in developing novel cell culture materials that are capable of supporting the expansion and directed differentiation of neural stem cells.

Dr Alys Griffiths
Alys.Griffiths@sheffield.ac.uk

School of Medicine and Population Health

I conduct qualitative research to understand the experience of living with long term conditions such as MND, dementia and cancer. I am particularly interested in the design and evaluation of complex interventions within social care.

Offering PhD opportunities in the following areas:

  • Improving social care for people with long term health conditions
  • Designing and evaluating complex interventions for social care
  • Assessment and diagnosis experiences for people with MND
  • Emotional labour of conducting research with people with long term health conditions
Dr Olena Mandrik
o.mandrik@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

My research interest is in evaluation of healthcare interventions through modelling the long-term clinical outcomes and cost-effectiveness.

Specific areas of interest:

  • Evaluations of public health programmes
  • Screening and early detection
  • Natural history disease modelling
  • Cancer modelling
  • Calibration of the models
  • Transferability of models and cost-effectiveness studies
  • Global research
Professor Timothy Skerry
t.skerry@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research interests

My research falls into 2 areas. First, I have a long standing interest in bone biology, particularly the way that the skeleton responds to exercise and specifically the cellular and molecular mechanisms behind that response. My second area of interest is in the development of a new therapeutic target for cancer and other diseases targeting a receptor mechanism with novel chemical and biological agents.

Miss Bethany Taylor
btaylor3@sheffield.ac.uk

School of Allied Health Professions, Nursing and Midwifery
Research Interests
 
My interest lies in conducting research with patients, family carers and health care professionals to learn from their experiences and improve service provision and care delivery. Recently, my research has focused on the experiences of people affected by mesothelioma, a rare cancer. I have a particular interest in the communication and information needs of patients and families, decision making and inequalities in accessing care and support. I am a research fellow at the Mesothelioma UK Research Centre. 
 
Research methods
Qualitative methods 
Mixed methods studies
Participatory methods 
Dr Joanne Thompson
j.thompson1@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

My current research is focused around the Social Accountability of Medical Schools, the impact on medical students and community organisations working in partnership with the university. This involves supporting students to become more aware of health inequity and social determinants of health and the broader implications for society.


My background is in academic psychology and counselling and I have a longstanding interest in the psychosocial impact of illness, in particular in relation to cancer survivorship and the management of children with long term conditions

Dr Ruth Thompson
r.h.thompson@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

It is commonly understood that DNA damage is largely sensed and repaired in interphase and it is proposed that DNA repair is repressed in mitosis due to the risk of telomere fusion.Cancer treatments such as chemo and radiotherapy induce massive amounts of DNA damage leading to cell death of rapidly dividing cells.  Some cancers have developed resistance to these agents by repairing the damage prior to cell division. For this reason, drugs which target the well known interphase checkpoints are rapidly being developed for use in the clinic. Drugs such as these however could be substantially less effective if there were also a DNA damage checkpoint in mitosis.

The aim of my research is to understand what happens when a cells with damaged DNA enters mitosis due to dysfunctional interphase checkpoints. I aim to understand the signaling molecules and pathways involved and hope to uncover the mechanism by which DNA damage is sensed and targeted for repair in mitosis. Understanding and inhibiting this checkpoint could lead to sensitisation of cancer cells to standard anti-cancer agents and thus represents a site of novel therapeutic intervention. 

Dr Stephen Brown
stephen.brown@sheffield.ac.uk
Personal Webpage

School of Biosciences

Research interests

My laboratory researches Human diseases, using 2D and 3D models. We have a particular passion for making Human organoids derived from induced pluripotent stem cells, as they are a more robust model than non-Human counterparts. Colorectal cancer is one of the major killers in the world and we are taking a number of novel approaches to learn how this disease progresses and to see if we can understand more about it using our organoids. As part of this work we use functional genomics, siRNA genome screens, drug screening and our cell and organoid models of Human disease.

Read more at the Sheffield RNAi Screening Facility

Professor Endre Kiss-Toth
e.kiss-toth@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research interests

My group is interested in identifying novel regulators of inflammatory signal transduction, characterising their basic mechanism of action, as well as validating some of these novel genes as potential drug targets for therapeutic intervention in chronic inflammatory diseases.

Much of our recent work has been focussing on studying the biological importance of the tribbles (TRIB) family of pseudokinases in cell types that are relevant to the development of cardiovascular disease.

In addition, we have also been collaborating closely with several research groups, from the US and Europe to characterise the role tribbles proteins play in the development and progression of cancer.

Most recently, we begun to develop approaches that enable us to selectively target TRIBs with the aim to use these as a platform for future drug development.

To support our research goals, we have established a global network of collaborators to pursue joint projects that aim to understand the importance of tribbles in cell biology, both in health and disease.

Professor Nicholas Latimer
n.latimer@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research interests

My research interests focus on economic evaluation methodology, with a particular emphasis on the incorporation of survival analysis within economic models. My doctoral and post-doctoral research has focused primarily on methods for adjusting survival estimates in the presence of treatment switching - that is, when patients in the control group of a clinical trial switch onto the experimental treatment, thus confounding estimates of the treatment effect (where the relevant question for an economic analysis is what would have happened if control group patients did not receive this experimental treatment). Adjustment methods are primarily from the causal inference literature, and I have a related interest in the use of causal inference methods to estimate comparative effectiveness from registry datasets, particularly in the area of cancer.


Professor Carl Smythe
c.g.w.smythe@sheffield.ac.uk
Personal Webpage

School of Biosciences

Career history

  • 2002 – present: Professor of Cell Biology, Department of Biomedical Science, University of Sheffield
  • 2004 – 2006: Head of Department, Department of Biomedical Science, University of Sheffield
  • 1992 – 2002: Principal Investigator at MRC Protein Phosphorylation Unit, University of Dundee
  • 1989 – 1992: American Cancer Society Senior Research Fellow, University of California, San Diego
  • 1985 – 1989: British Diabetic Association postdoctoral research assistant at MRC Protein Phosphorylation Group at University of Dundee
  • 1981 – 1985: PhD Department of Biochemistry, Trinity College, University of Dublin

Research interests

Chromosome Integrity - Chromosomes in eukaryotes control their environment to ensure that genomic integrity is maximised. We are interested in understanding mechanisms of genomic integrity operating at the molecular and cellular level, and determining the consequences when they fail.

Read more on research in the Smythe laboratory

Dr Asra Aslam
a.aslam@sheffield.ac.uk
Personal Webpage

School of Information, Journalism and Communication

Research Interests

My research focus around designing and applying Artificial Intelligence (AI) and Machine Learning (ML) models in two major areas:

1. Computer Vision: Industry and Academics research projects in areas of Object Detection (YOLO, SSD, RetinaNet), Image Segmentation (Segment anything Model SAM, U-Net), Image Classification (MobileNet, ResNet, VGG, DarkNet), Few Shot Learning, 3D Point Cloud (PointNet, SPVCNN), and these approaches with Supervised, Semi-Supervised, and Unsupervised
Learning.

2. Health Sciences: Electronic Health Records, Multiple Long-Term Conditions (MLTC), Multimorbidity, Temporal Graph Neural Networks, Codelists (SNOMED, MedCodes), Designing Deep Neural Networks for diagnosing medical conditions like Arthritis, Hospital Admissions, Face Injuries, Skin Cancer, Brain Tumour, and other use cases.

3. Other research areas: Internet of Multimedia Things (IoMT), Publish Subscribe Paradigm Multimedia Event Processing (MEP), Complex Event Processing (text data queries).
Please find details in research publications at:

(https://scholar.google.com/citations?user=bfXlzuMAAAAJ&hl=en)

Codings, Tools, and Implementation (Help for PhD Students in): Python, Tensorflow, CUDA, Pytorch, Pytorch Lightening, TensorFlow, Keras, Pandas, NumPy, SciPy, Jupyter Notebooks, GPU servers, Visual Studio, entwine, CloudCompare, MLflow, Jira, confluence.

Major Research Areas can be summarised as: Computer Vision, Deep Neural Networks, Smart Cities, and Health Sciences.

Research Supervision

I am looking for PhD students interested in Interdisciplinary projects involving Artificial Intelligence (AI) and Machine Learning (ML) applications in multiple domains. Some of the potential examples are included below:

- AI based models for processing Heterogenous data for Early Diagnosis of Life-threatening Conditions.
- Asset Inspection with 3D Image Segmentation.
- Generative AI Models for Skin Cancer Detection on Phone Images.
- Automatic generation of Object Detection Dataset (ObjectNet).
- Pattern Detection in Patient Trajectories using Temporal Graph Neural Networks.

Dr Mirre Simons
m.simons@sheffield.ac.uk
Personal Webpage

School of Biosciences

Taking an evolutionary perspective I work on the adaptive value of differences in ageing between and within species to reveal fundamental aspects of the aging process. In this context I have worked on trade-offs concerning reproductive effort and sexual signalling. To increase reproductive effort, I used various experimental manipulations in three-spined stickleback.

I also studied senescence and sexual signaling of bill coloration in zebra finches. Both during my PhD at the University of Groningen (The Netherlands). Moreover I have conducted several meta-analyses concerning the biology of ageing and sexual signaling (see my publications list). For my postdoctoral work at the University of Sheffield (UK), Molecular Ecology, I have studied senescence and telomere biology in an insular island population of wild house sparrows.

The current focus of my lab group is on the mechanisms of ageing and modulation by diet. We study demographic ageing, molecular mechanisms of dietary restriction and age-related disease (dementia and cancer). To do this we use the fruit fly, a functional genetics powerhouse. We use a combination of transcriptomics, proteomics and metabolomics to identify candidate mechanisms. Please refer to our lab web pages for more information and/or contact me. There are always opportunities to collaborate or come work in my lab.

I focus on the following topics:

  • Demography of mortality
  • Dietary restriction
  • Costs of reproduction and the evolution of ageing
  • Biology of cancer and cellular senescence
  • Telomere length and dynamics
Professor Tuck Seng Wong
t.wong@sheffield.ac.uk
Personal Webpage

School of Chemical, Materials and Biological Engineering

The research in Wong group focuses on applying advanced protein engineering technique, specifically directed evolution, to tailor the properties of enzymes for industrial and pharmaceutical applications as well as to elucidate the design principles used by Nature. There are three key areas that we are currently working on:

1) Development of novel molecular biology tools to advance the field of directed evolution (e.g., method to create high quality mutant library).
2) Application of directed evolution to improve existing properties of industrially relevant enzymes (e.g., cytochrome P450s, carbonyl reductases, aromatic peroxygenases and hydrolases) or to create novel functions.
3) Development of computational tools to facilitate and expedite experimental design (e.g., method to analyse genetic diversity).

One of our current research projects is to develop biological carbon dioxide capture and utilization (CCU) strategies for bulk, fine and specialty chemical syntheses, capitalizing on our interest in directed evolution and synthetic biology.


Complementing protein engineering, we also apply a wide array of biophysical techniques to study various properties of biomolecules (e.g., structure, stability, oligomeric state, protein-protein interaction, and protein-DNA interaction etc.). We characterize proteins and complexes involved in cancer, ageing and mutational diseases.

Research Topics:

  • Protein Engineering (Directed Evolution)
  • Biocatalysis and Industrial Biotechnology
  • Synthetic Biology
  • Biological Carbon Dioxide Capture and Utilization
  • Biophysics
  • Cancer and Ageing
Research Personnel:
  • Pawel Jajesniak (Poland)
  • Hossam Eldin Omar Ali (United Kingdom)
  • Amir Zaki Abdullah Zubir (Malaysia)
  • Abdulrahman H. Alessa (Saudi Arabia)
Dr Nicola Green
n.h.green@sheffield.ac.uk
Personal Webpage

School of Chemical, Materials and Biological Engineering

 Nicola's research portfolio can be divided into these main areas:

The generation and testing of biohybrid scaffolds for tissue engineering

Biohybrid scaffolds are synthetic scaffolds enhanced with biological components derived from the extracellular matrix (ECM). Nicola's research focuses upon using cells to generate this ECM, enhancing the process through environmental cues and evaluating the efficacy of the resulting scaffolds.

Characterisation and modulation of the cellular response to biomaterials at multi-length scales

This research investigates the heterogeneity of scaffolds and assessing the cellular response to this at a range of length scales. This work aims to allow a targeted development of biomaterials to modulate cellular behaviour through specific changes in the biomaterial properties.

Creation of scaffolds for replacement and repair of multiple tissue types

Scaffolds to replace or repair one cell or tissue type only do not fit many clinical needs. This research area centres around developing scaffolds structured to fulfil the needs of the different cell types that make up more complex structures, and the creation of localised environments to promote particular cellular responses, with a focus upon the musculoskeletal system.

Tissue engineered constructs as in vitro models

This aspect of the portfolio considers the development and use of tissue engineered constructs as models of disease pathogenesis and progression, and for drug pipeline testing. It has included the development of a models for the early events in cancer, and investigation of metastasis and invasion.

Dr Luke Green
l.r.green@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Bacterial infections such as sepsis and meningitis are huge problems worldwide. Bacterial adhesion to host cells is essential for both colonisation and infection. New therapies to prevent adhesion could significantly decrease disease and reduce the burden of antibiotic usage.

We have identified a superfamily of proteins which appear to control bacterial adherence to epithelial cells. These proteins, the tetraspanins, do not act as receptors but organise and cluster hijacked host proteins in to 'adhesion platforms' to allow efficient adherence and entry of bacteria to cells. Blockade of these proteins leads to a significant reduction in bacterial adherence of many Gram negative and Gram positive bacteria. Using a variety of techniques we identify members of these adhesion platforms and new ways to inhibit their function during infection. Furthermore, we investigate changes to the composition of both bacterial membrane proteins and host adhesion platforms during tetraspanin-mediated infection utilising a number of bacteria as models.

We are also interested in the importance of the bacterial microbiome in humans and how dysbiosis of this flora can affect various diseases ranging from skin afflictions to cancer. We currently run a number of studies which utilise Oxford Nanopore Technology sequencers to delineate the microbiome.

Professor Barend van Hout
b.a.vanhout@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

I have extensive experience in modelling and have contributed to the methodology of economic evaluation in various areas. In 1993 I was one of the earliest researchers to apply discrete event models and was the first to apply a non-parametric method to estimate costs in the presence of censoring[1]. In 1994 I was the first to apply Fieller´s approach to calculate confidence intervals around cost-effectiveness ratios, and I introduced the acceptability curve, which is now a well known concept in cost effectiveness analysis[2]. In 1996 I was one of the first to apply probabilistic sensitivity analysis[3]. In 2000 I was one of the initial people to explore Bayesian techniques in economic evaluation[4]. I have had work published on discounting[5] and estimating utility functions[6].

I am one of the founding members of the EuroQol group and I currently enjoy chairing the valuation task force within the EQ-5D group. My experience covers several therapeutic areas, including renal disease, cancer, osteoporosis, sepsis, schizophrenia, blood safety and most notably cardiovascular disease. My main interest concerns the use of elegant techniques, mostly to solve practical problems, but sometimes also because of the elegance itself.

Professor Richard Ross
r.j.ross@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Research Interests

The focus of both my clinical and basic research is on optimising pituitary hormone replacement. My group have identified and characterised uncommon mutations in the growth hormone receptor which have led to fundamental observations on the mechanism by which the growth hormone receptor signals through a pre-formed dimer. This work has led to a greater understanding of the regulation of growth hormone secretion and recently the group have developed a long acting form of growth hormone which has exceptional pharmacokinetic properties that means administration may only be required once a fortnight or once a month. This work was published in Nature Medicine in 2007.

The Clinical Research Programme has been investigating different regimens for replacing cortisol, testosterone and oestrogen in hypopituitary, hypogonadal and adrenal insufficient patients. The group have designed a new modified release form of hydrocortisone, Chronocort, which in phase 1 studies has proven to replicate the normal circadian rhythm of cortisol. This work is currently being taken through to phase 2 studies in congenital adrenal hyperplasia patients. Other work has examined the incidence of hypogonadism in cancer survivors and optimising oestrogen replacement in young women of fertile years.

I co-chair the Endocrine Unit Management Team which consists of 6 Consultant Endocrinologists and runs a number of unique and innovative specialist clinics in the Health Care Trust including: Pituitary Clinic, Transition Clinic for Paediatric Endocrinology, Late Effects Clinic for Cancer survivors, Joint Surgical Endocrine Clinics, Obesity Clinic, Genetic Endocrine Clinic and a Pituitary Multidisciplinary Team.

Publications and Patents: 234 publications during career, 34 publications in the last 5 years, Scopus h-index of 34, 7 papers cited over 100 times, 2 over 200 times and 1 over 300 times.  35 patents granted from 7 independent patent families.

  1. Patent granted 2010: C Strasburger, M Bidlingmaier, Z Wu, G Matarese, R Ross. Leptin antagonist and method for quantitative measurement of leptin. US 7,807,154 B2
  2. Patent granted 2012: R Ross, P Artymiuk, J Sayers.  Fusion protein compromising growth hormone and growth hormone receptor. US 8,173,782 B2
Dr Mark Bass
mark.bass@sheffield.ac.uk
Personal Webpage

School of Biosciences

Research interests

Healing defects are one of the largest current health challenges, with chronic wounds frequently requiring amputation of the affected limb. In 2008, 200,000 UK patients were suffering chronic wounds, costing the health service £3.1 billion annually.  Since then, a 26-49% increase in risk factors such as age and diabetes has made the situation worse. 

Upon wounding healthy skin, inflammatory cells combat infection, fibroblasts migrate into the wound bed and contract the defect, and finally re-epithelialisation closes the gap.  However, these processes become less efficient with age and risk factors such as diabetes, obesity or smoking, eventually leading to the formation of chronic wounds that include pressure ulcers, venous leg ulcers and diabetic foot ulcers.

 

We are investigating the processes of fibroblast recruitment and wound re-epitheliasation with a view to developing new therapies to promote healing.  Part of our work focuses on the signalling by adhesion receptors that detect the changes in skin upon injury.  We investigate the signalling through Rho-family GTPases that regulate cell migration and receptor trafficking.  We are finding that these pathways influence wound healing, but in more recent work we are finding that they also impact on cancer progression.  Importantly, our projects in collaboration with the hospital and industry are translating our advances in basic biomedical science into practical application.  We have developed ultrasonic strategies that reduce healing time by 40% and can be applied to human patients.  By doing so, we are able to investigate fields that span from basic molecular science fields of signalling and migration to therapeutic outcomes.

Professor Iain Coldham
i.coldham@sheffield.ac.uk
Personal Webpage

School of Mathematical and Physical Sciences

Research Interests

New methodology in organic chemistry.

Synthetic chemistry depends on reliable, high-yielding and selective reactions that access a wide variety of different structures. The discovery of new methods in synthesis is crucial to expand the range of novel compounds that can be made easily. Especially important is the development of new carbon-carbon bond-forming reactions. Our research group is studying the use of organometallic compounds in asymmetric synthesis, especially for carbon-carbon bond formation of nitrogen-containing compounds, prevalent in many biologically active molecules. We have found that 2-lithiopyrrolidines, piperidines and other cyclic amines undergo dynamic resolution in the presence of a chiral ligand (L*), leading to highly enantioenriched 2-substituted cyclic amine products. We have determined the kinetics of enantiomerization of several chiral organolithium compounds.

Synthesis of biologically active compounds.

We are using dipolar cycloaddition chemistry to access a variety of alkaloid structures. Intramolecular cycloadditions provide an efficient means to build up bicyclic and polycyclic ring systems in a rapid and stereocontrolled way. We have shown that this chemistry is applicable to the synthesis of the core ring system of the alkaloid manzamine A, which has significant biological activity (anti-cancer, anti-malarial, and other activity). One dipole that we use is an azomethine ylide, that we make by condensation of a secondary amine with an aldehyde. Intramolecular cycloaddition sets up two new rings and up to four new stereocentres in a single step. We have prepared simpler analogues of manzamine A and other heteroaromatic compounds to probe their biological activity.

Recently, we have found that primary amines (such as amino-acids, amino-esters, hydroxylamine) can be used to condense with an aldehyde and promote a cascade process involving imine formation, cyclization, ylide formation and cycloaddition all in one pot. This chemistry provides an efficient method to prepare three rings directly from an acyclic aldehyde in a stereocontrolled way and has been applied to the total syntheses of several alkaloids (such as aspidospermidine, aspidospermine, quebrachamine and myrioxazine A).

Dr Luke Green
l.r.green@sheffield.ac.uk
Personal Webpage

School of Clinical Dentistry

Research interests

Bacterial infections cause a diverse range of disease ranging from superficial skin infections to periodontitis to severe infections such as sepsis and meningitis. This coupled with rising antimicrobial resistance have led to increasing burdens of infection and are therefore a significant health concern worldwide. Bacterial adhesion to host cells is essential for both colonisation and infection. New therapies to prevent adhesion could significantly decrease disease and reduce the burden of antibiotic usage.

We have identified a superfamily of proteins on host cells which appear to control bacterial adherence to epithelial cells. These proteins, the tetraspanins, do not act as receptors but organise and cluster hijacked host proteins into 'adhesion platforms' to allow efficient adherence and entry of bacteria to cells. Blockade of these proteins leads to a significant reduction in bacterial adherence of many Gram negative and Gram positive bacteria. Using a variety of techniques we have identified members of these adhesion platforms and new ways to inhibit their function during infection. Furthermore, we investigate changes to the composition of both bacterial membrane proteins and host adhesion platforms during tetraspanin-mediated infection utilising a number of bacteria as models.

We are also interested in the importance of the bacterial microbiome in humans and how dysbiosis of this flora can affect various diseases ranging from skin afflictions to cancer. We currently run a number of studies which utilise Oxford Nanopore Technology sequencers to delineate the microbiome.

 

 

Dr Catarina Henriques
c.m.henriques@sheffield.ac.uk
Personal Webpage

School of Medicine and Population Health

Tissue Repair and Immunity in Ageing (TRIA)

Why we age and whether we can therapeutically prevent associated diseases has been my continued research motivation. And this is because age is the greatest risk factor for chronic diseases such as cancer, frailty, muscle atrophy, arthritis and many others. This means we are living longer than ever before, but with a heavy burden of disease which impacts on our quality of life and poses serious socio-economical challenges we must meet.
Ageing is underlined by a progressive decline in tissues ability to repair and maintain themselves. This is what is called tissue homeostasis impairment and sets the ground for age-associated diseases. A key mechanism contributing to this is telomere shortening and dysfunction. In organisms with restricted telomerase activity, which is the case of humans and zebrafish, telomeres shorten and get damaged with ageing, causing cells to die or become senescent. Senescent cells no longer divide and secrete factors that somehow impair the repair capacity of our tissues and organs, thereby contributing to disease.

Tissue homeostasis requires a tight balance between the clearance of senescent and damaged cells by the immune system and the replenishing of new cells from the stem cell niche.

My research programme focuses on understanding the interplay between immune regulation and tissue homeostasis in health and with ageing, using zebrafish as a model. My ultimate aim is to identify therapeutic targets that can be used to incentivate tissue rejuvenation and ameliorate multiple co-morbidities of ageing

Dr Grant Hill
grant.hill@sheffield.ac.uk
Personal Webpage

School of Mathematical and Physical Sciences

Research Interests

 

Research JGH

My research interests revolve around the 'how' and 'why' of Chemistry, particularly in terms of electronic structure. A fascination with this subject has led me to investigate, for example, how the aromaticity of organic molecules changes during the course of a pericyclic reaction, why various approximations in quantum mechanics affect calculated thermodynamics and spectroscopy, and how intermolecular interactions are responsible for the activity of selected anti-cancer pharmaceuticals and halogen bonding.

It often transpires that a convincing description of chemical systems requires a high level of accuracy, which may be out of reach with the existing tools of computational chemistry. This has motivated my interest in developing new tools that allow accurate calculations to be carried out on larger, more complex systems. Examples include a method for efficiently producing a balanced description of both the hydrogen bonding and pi-stacking in nucleic acid base pairs, ensuring that cutting edge calculations can be carried out on a wide variety of chemical elements through the design and optimisation of Gaussian basis sets, and techniques for exploiting the well-controlled behaviour of certain calculations to produce accurate thermochemical and spectroscopic data from first principles.

Although many of my research projects have been entirely theoretical, I have several on-going collaborations with experimental groups in areas such as intermolecular interactions and molecular reaction dynamics. The results of calculations carried out in my research group helps guide their work in the lab, and is often an invaluable step in interpreting the results.

Dr Ian Sudbery
i.sudbery@sheffield.ac.uk
Personal Webpage

School of Biosciences

How do cells integrate information to make decisions about what genes should be expressed at a given time and in a given place? How do these processes malfunction to produce disease states? The correct regulation of gene expression is essential for the proper functioning of the cell, and incorrect regulation of genes is central to the mechanisms of many diseases. My interests rest in understanding how the many levels of eukaryotic gene regulation work together to perform these functions, using computational and functional genomics tools.

The role of microRNAs in regulatory networks


microRNAs (miRNAs) are short, single stranded RNAs that act to down regulate the expression of their targets by transcript destabilisation and translational inhibition. What roles to these molecules play in the information processing systems of the cell? How might these roles differ from that provided by transcriptional inhibitors? We know that miRNAs are found enriched in different topologies of network motifs than transcription factors. What might explain this?

Mathematical modelling suggests that miRNAs might threshold the expression of their target genes, only allowing protein production once transcription exceeds a particular rate. However, thus far experimental tests of this model are lacking in realistic in vivo settings. We are studying evidence that might speak to the applicability of this model in real biology, and studying the consequences of this behaviour on regulatory networks and the identification of miRNA targets.

Misregulation of chromatin structure in disease


A cell’s DNA does not exist as a single extended string of nucleic acids in the way often imagined, but rather is packed and folded in a myriad of ways to form a complex three dimensional structure. At least some of this structure is thought to be important for the regulation of gene expression. Transcription of metazoan genes is regulated by sequences known as enhancers which integrate diverse signals to make decisions about expression, and then communicate these decisions through their interactions with promoters. This communication is thought to take place via physical interactions between promoters and enhancers.

Together with collaborators from the Imperial University we are investigating how this three dimensional structure might contribute to the miss-regulation of gene expression in both monogenic disease and cancer using high-throughput, next-generation sequencing based assays of chromatin conformation.

Professor Jonathan Waltho
J.Waltho@sheffield.ac.uk
Personal Webpage

School of Biosciences

Research Interests

Our laboratory focuses on the use of high field NMR spectroscopy to determine the structure and function of proteins and how they fold from their fully unfolded states. Our studies address both fundamental aspects of protein biophysics and dynamics, and the investigation of the biomedical targets and their inhibition.

Recent highlights include the structure determination and characterisation of the solution dynamics of the human intracellular cysteine proteinase inhibitor stefin A. Proteins of this family inhibit enzymes central to the invasion of the body by foreign organisms (e.g. trypanosomes that cause African Sleeping sickness) and the entry of metastatic cancer cells into new tissues.

In addition, the absence of the protein stefin B was recently the first identified genetic cause of epilepsy.

Structure and dynamic measurements of stefins provide insights into means of developing small molecule pharmaceuticals that mimic the protective function of this class of proteins.

Understanding how proteins fold is both a major goal from a viewpoint of fundamental biochemistry, and is of growing biomedical importance owing its implication in a variety of neurodegenerative diseases.

Diseases ranging from Alzheimer’s, through amyloid angiopathy to the prion diseases, CJD and BSE, appear to utilise partially and misfolded states of proteins.

We have shown how NMR can be used to determine structural and dynamic information of such states, which provide a basis for identifying where and how to interrupt amyloidogenesis before the onset of neurodegeneration. We focus on three proteins in this regard, cystatin C, human prion protein and phosphoglycerate kinase (PGK).

Enzymes that catalyse phosphoryl transfer include kinases, ATPases and phosphatases, and therefore constitute arguably the most important group of enzymes. They increase the reaction rate by up to 1020-fold - a truly remarkable rate increase.

Studies by our group, reported in Angewandte Chemie 2017 56:4110, use a combination of X-ray crystallography, NMR, and computational analysis, using metal fluorides as analogues of the phosphate group.

They show how these enzymes use a combination of precise geometrical positioning, charge balance, and control of hydrogen bonds, to achieve their rate enhancements. They also show how much we still have to learn.

Professor Simon Johnston
s.a.johnston@sheffield.ac.uk
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School of Medicine and Population Health

When the immune system does not function properly, for example, in HIV infection (the virus that causes AIDS), cancer and old age, we are vulnerable to microbes that normally do not cause disease. One such microbe is the fungus Cryptococcus that causes an estimated 600,000 deaths each year. I want to understand why we become vulnerable to infections such as Cryptococcus.

We already know that Cryptococcus can avoid parts of our immune system, for example it escapes immune cells whose job it is to eat and digest microbes, but we do not know how single aspects like this come together to cause life-threatening disease. The zebrafish represents a unique opportunity to study these interactions as they are transparent in their early life and have an immune system that is similar to our own. I have developed ways to look at zebrafish in three-dimensions over time that mean I can study the individual behaviour of many immune cells and microbes at the same time during infection. I believe that this will dramatically further our understanding of how microbes cause disease, how the immune system is able to respond and how to develop new treatments and therapies.

Technical Summary

Understanding of the macrophage interaction with pathogens is crucial for the study of infectious disease, with many important pathogens known to manipulate phagocyte function (e.g. HIV, Tuberculosis, Salmonella). However, there are very few examples of where this interaction can be studied at a cellular level, in vivo during infection, especially with high-resolution light microscopy, a technique that has proved fundamental for insights in vitro.

Cryptococcus is a fatal fungal infection of humans causing death through meningitis. C. neoformans is a significant pathogen of the immunocompromised, especially AIDS patients, and causes an estimated 600,000 deaths per year. In contrast, C. gattii is predominantly a pathogen of immunocompetent individuals and although predominantly localised to the tropics and sub-tropics, there are increasing numbers of cases outside of this region, in particular the Vancouver Island Outbreak (VIO), which highlights how particular groups of C. gattii are becoming hypervirulent.

By evading or manipulating phagocytes, particularly macrophages, Cryptococcus is able to cross the immune barriers that normally prevent fatal disseminated disease. Current studies focus on in vitro analysis in isolated (mammalian) cells, such as macrophages or in vivo studies in rodent hosts. However, such approaches are unable to capture the complex cellular events that define how this fatal disease progresses or is stopped. Therefore, I have developed a new integrated model of cryptococcosis in zebrafish to simultaneously study host and pathogen factors that determine disease progression and outcome in vivo. Zebrafish (Danio rerio) are proven models of human disease as well as immune cell and infection biology and are unparalleled for this work due to the ability to perform in vivo sub-cellular resolution imaging in the entire body of a living vertebrate.

Professor Rob Short
rob.short@sheffield.ac.uk
Personal Webpage

School of Mathematical and Physical Sciences

Rob studied Chemistry (BSc) and Physical Chemistry (PhD) at the University of Durham (UK) and joined the Department of Engineering Materials at the University of Sheffield in 1988, where he held the Chair of Material and Biomaterial Chemistry from 2001. During this period, Rob helped develop a materials-cell technology (myskin) for treating severe burns and scalds; adopted in the UK by the NHS, this technology was used over a decade in all the UK’s major burns centres. Rob also established Plasso Technology, an advanced materials for life science research company. Plasso developed technology that now underpins a range of products (PureCoatTM) sold globally for cell culture and cell therapy.  

In 2006, Rob joined the University of South Australia, where he held the positions of Director of an advanced manufacturing research institute, Dean of Research and Pro Vice Chancellor and Vice President. At the invitation of the Minister of Education he served on the Australian Research Council's College of Experts for three years.  

In Australia, he successfully co-led bids for an A$110M national centre for wound management innovation and a A$60M national centre for cell therapy manufacturing. Both have resulted in successful innovations in wound care and cell therapy. These include the companies, Carina Biotechnology (www.carinabiotech.com), which is developing a novel CAR-T cell therapy for solid (cancer) tumours and Tekcyte (www.tekcyte.com), whose products include a cell-based therapy for non-healing wounds, which entered clinical trials at the beginning of 2022.   

Rob returned to the UK as the Director of the Lancaster Material Science Institute, where he helped establish the Material Social Futures Centre for Doctoral Training, focusing on how materials’ innovations shape society (and vice versa). See Material Social Futures | Lancaster University.  This centre is training 22 PhD students. 

Last year, Rob cofounded with Dr Endre Szili (UniSA) Plasma-4 (www.plasma-4.com) a company that is developing novel plasma (ionised gas)-materials technology for the treatment of a range of clinical indications.  

Over his career, Rob has won over A$250M of grants and investments, including ARC Discovery, Linkage etc, CRC, and in the UK, EPSRC, Wellcome, Leverhulme, Royal Society etc. He has supervised to completion 25 PhDs and 30 post-doctoral researchers. He has published over 250 substantive peer reviewed papers. 

In 2013, Rob was elected to the Australian Academy of Technological Sciences and Engineering.  

He is a fellow of the Royal Society of Chemistry and Institute of Materials, Minerals and Mining. 

Rob rejoined the University of Sheffield in October 2022.