The JBU’s staff and students focus on research projects across a wide range of topics associated with bladder function and disease. Work in the lab spans areas of fundamental research to clinical and applied projects.
Jenny Southgate began her career at the Imperial Cancer Research Fund (ICRF) in London, where she obtained a degree from the Institute of Biology, followed by a PhD from the University of Leeds. She moved to Leeds in 1990, where she headed a research group based in the ICRF Cancer Medicine Research Unit at St James's University Hospital, University of Leeds.
She took up the post of Director of the Jack Birch Unit in October 1999. This post is sponsored by a programme grant from York Against Cancer.
Jenny’s research interests encompass the cell/molecular biology of human epithelial tissues and their cancers, primarily focusing on the urothelium of the urinary bladder. Her strategy has been to develop cell and tissue culture systems for normal human urothelial (NHU) cells which can be used to examine the pathways that regulate tissue homeostasis. The research has led to approaches that enable NHU cells to be propagated in vitro and manipulated to form functional differentiated tissues. This is used as a platform for gaining insight into bladder diseases including interstitial cystitis and cancer. A potential application of the research being explored is the use of regenerative medicine approaches (tissue engineering stem cells and biomaterials) to restore bladder function following trauma or diseases, such as cancer.
I have worked in the Jack Birch Unit since completing my PhD and have previously held Yorkshire Enterprise, BBSRC Enterprise and Wellcome Trust VIP Fellowships. In late 2021, I was awarded a Kidney Research UK Intermediate Fellowship to continue my work on BK virus. I am very grateful for the broad support I have received, including the York Against Cancer funding that enabled the initial work on BK virus (published in Oncogene in 2022) and the extension of my fellowship by an additional year of financial support from my University and Department.
My primary focus is developing evidence relating to the hypothesis that BK virus infections of the urinary tract lead to the development of the mutations that cause bladder cancers. This research programme includes cell biology, clinical/translational work and public and patient involvement (PPI). Our PPI is critical to ensure the research remains focussed and that the data drives evidence-based change in clinical practice to improve the lives of patients.
BK polyomavirus is a common childhood viral infection. BK virus is known to establish a persistent/latent infection of the kidney that survives into adulthood and can become reactivated. When BK virus becomes reactivated it can be detected in the urine. We found that BK infection of the human bladder epithelium (called “urothelium”) leads to the activation of anti-viral enzymes (called “APOBECs”) which damage the genome, potentially leading to cancers.
Much of my work involves “genomic” and “transcriptomic” methods, which are used to examine how the genes of cells can be damaged and the ways in which the genes are used. A particular recent focus of mine has been the diagnostic patterns of DNA-damage left in the genome by specific events, known as “mutational signatures”.
We have previously described the mutational signature of a smoke carcinogen’s effects on the urothelium. My Kidney Research UK fellowship will take the next step and collect the mutational signatures of viral infection and compare them to tumours, so the risk BK infections pose can be established.
We are studying the genes which give human urothelium its unique properties such as the urinary barrier, remarkable wound healing and detoxifying enzymes. Our approach is to start from an understanding of how the normal (non-cancerous) tissue functions and then evaluate how features of the tissue’s specific biology might be hijacked by cancers to support their unregulated growth.
Some cancers retain features that are associated with the normal tissue and these retained features can give us clues about how the tumour functions. If a particular cancer has retained a feature of the normal tissue, it is likely that this is associated with tumour survival/growth and we need to understand how its role has been perverted in this context.
I have a long-standing interest in the adaptive responses of the bladder epithelium (“urothelium”) to urinary exposures (specifically toxins and viruses). The urothelium spends your whole life exposed to concentrated toxins in the urine. Some of these toxins damage the DNA and we are looking at whether certain chemicals leave their signature on the DNA in the form of specific mutation types. These “mutational signatures” might help explain the cause of the cancer in each individual and help guide treatment approaches.
Andrew completed his BSc Biological Sciences (Hons. Evolutionary Biology) degree from The University of Edinburgh in 2013. He gained his PhD from The Roslin Institute in 2017 after completing a predominantly bioinformatics four-year BBSRC CaSE studentship on avian endogenous retroviruses, researching their impacts on physiology, health and commercial productivity. Andrew then made the move to York, and to the Jack Birch Unit, as a postdoc working on transcriptomic characterisations of benign and malignant bladder disease, as well as deriving cancer-relevant transcriptomic signatures from experimental models. Andrew began the Mason lab within the Jack Birch Unit in 2019 following a competitive interview for the York Against Cancer 30th Anniversary Research Fellowship (and proleptic lectureship) in Cancer Informatics, with the lectureship starting in November 2022.
The broad aim of the Mason lab is to use sequencing data to understand carcinogenesis, and to stratify cancers and other diseases in biologically and clinically relevant ways to derive more personalised treatments. The lab's research covers two main areas: characterising human urothelial carcinoma, and understanding the impacts of (endogenous) retroviral interactions in avian and human cancers. Building on the wealth of experience in the wider Jack Birch Unit, the lab's main focus is on urothelial carcinoma, working with large cohort studies such as The Cancer Genome Atlas and the Genomics England 100,000 genomes project, where Andrew is one of the bladder cancer bioinformatic leads. Current work utilises transcriptomic (bulk and single-cell), genomic and lipidomic approaches.
Andrew is also keen that the Mason lab provides a platform for emerging bioinformatics-focused researchers to gain experience and grow into independent scientists, as well as driving improvements in bioinformatics and data science within the life sciences at York. In line with this ambition, Andrew was selected as an Elixir-UK Data Stewardship Training Fellow in September 2021.
Ros graduated from Liverpool University in 1993 with a BSc in Freshwater Biology. She started work at the University of York in 1998 working in the Medical Cryobiology Unit to research methods for cryopreservation of single cells and tissues. She joined the Jack Birch Unit in 2003.
Ros’ main role is the management of the unit’s tissue culture facility. This involves overseeing the smooth running of the tissue culture laboratory, providing training to staff, students and visitors. She also takes charge of isolating primary cells from tissue samples to establish urothelial cell lines and is involved in a number of research projects.
Richard graduated from the University of York with a BSc in Molecular Cell Biology in 2020. He then went on to study for an MSc in Bioinformatics at the University of Birmingham, before returning to York to join the Mason Lab and Jack Birch Unit in October 2021.
Richard is interested in using a variety of computational tools and workflows to process and analyse next-generation sequencing data, including RNA-seq and whole genome sequencing. Richard will offer bioinformatics assistance to other lab members to support the ongoing research within the group.
Jenny joined the group in January 2004 after obtaining a BSc in Cell Biology from Durham University and completed her PhD in 2016 whilst working part-time in the Jack Birch Unit. Jenny is primarily responsible for managing the histology, microscopy and immunochemistry facilities for the Jack Birch Unit, as well as providing research & training support for the group.
Jenny’s main research interest is in understanding the role of gap junctions in intercellular communication in regulating homeostasis and repair of normal and diseased or malignant urothelium.
Jo graduated from the University of York in 2002 with a BSc and MSc in Molecular Biology, followed by a PhD from the University of Manchester in 2006. She then returned to York and after completing a BBSRC funded Post Doc in the YCR Cancer Research Unit, took a career break in 2010 to look after her family. She then joined the Jack Birch Unit in 2011 as a research technician and was promoted from grade five to grade six in 2017.
Jo provides molecular biology support to all members of the group.
Claire graduated from Liverpool John Moores University with a BSc in Applied Biochemistry, followed by a PhD from the University of Sheffield. After completing a BBSRC-funded Postdoctoral research position in Manchester, Claire joined the Jack Birch Unit in 2000 on a Wellcome Trust-funded Postdoctoral position. She had a career break in 2013 and returned to the Jack Birch Unit as a Research Technician. Claire has experience in a wide range of cell biology and molecular biology techniques and offers support in these areas.
Claire is interested in mechanisms of urothelial differentiation and how this is affected in disease conditions including cancer, interstitial cystitis and urinary tract infection.
Claire established a method for differentiating normal human urothelial (NHU) cells. She discovered that differentiation is induced in NHU cells following activation of the nuclear receptor, PPARγ, which itself required inhibition of EGF receptor signalling. The gene expression programme induced during urothelial differentiation includes the uroplakins (UPK1a, UPK2, UPK3a), cytokeratins (CK20, CK13) and tight junction proteins (ZO1, ZO3, claudin 3), whilst CK14, a marker of squamous metaplasia is down-regulated. The PPARγ-induced differentiation acts indirectly on these differentiation genes via transactivation of a network of transcription factors, including FOXA1 and IRF-1. A subset of patients with interstitial cystitis were found to have urothelium with compromised potential to differentiate via the above PPARγ-induced mechanism.
More recently, she has been investigating the role of an acyl transferase in the generation of functional barrier, urothelial differentiation and wound repair.
My name is Syaffa and I’m from Malaysia. I am supervised by Professor Steve Smith in Electronic Engineering, Professor Jenny Southgate in Biology and Dr Dawn Walker from Computer Sciences at the University of Sheffield.
My PhD research focuses on the investigation of "white box" machine learning to characterise cell cultures through the analysis of time-lapsed spectroscopy that will involve technique to automated tracking of label-free cells and modelling of the Urothelium cells culture. Currently, many existing cell tracking approaches deteriorate from two main drawbacks that strongly depend on the staining of the cell culture and generate short cell trajectories. To allow the quantitative motility analysis of label-free cells, I plan to implement "white box" approached machine learning for interaction and migration tracking, which allow auto-tracking of label-free Urothelium cells culture in bright-field microscopy images.
This research will investigate ways of applying the technology to large datasets obtained from leading cancer hospitals we are forming collaborations with to establish a new methodology for detecting bladder cancer at an earlier stage than can currently be achieved. At the beginning of the study, time-lapse microscopy video on NHU was collected, which involved six wells/plates. All time-lapse microscopy sequence images are saved in tif (16 bit) raw image format and the image processing needs to be done to identify the cell, background, and noise. This process involves segmentation and clustering. The identification of cell tracks will allow more complex patterns of cell conduct to be analysed and quantified.
Such quantitative analyses will enhance our understanding of cells in health and disease interrelated and working. This research is potential to integrate the algorithm with the hardware where the image analysis will be in real-time based and will save time in detecting the cancer cell.
Ryan obtained an integrated Master’s in Biochemistry from the University of Oxford before moving to the Jack Birch Unit to study for a PhD. Ryan is funded by York Against Cancer and is supervised by Professor Jenny Southgate, Dr Simon Baker, and Dr Gareth Evans.
Fibroblast growth factor receptor 3 (FGFR3) is commonly mutated in bladder cancer to become activated, and is associated with low-grade and low-stage tumours, despite being classically considered as an oncogene. Ryan's project aims to understand the role of FGFR3 signalling in the normal urothelium, to gain insight into its role in bladder cancer. Ryan's project will also look at c-Src kinase, which is typically associated with a poor prognosis and metastasis in several cancers including colon and breast. However, the role of Src in bladder cancer and the normal urothelium is unclear, and it has been suggested that Src may play a protective role in bladder cancer. Ryan will investigate the role of Src in normal urothelium to better understand its involvement in bladder cancer.
Debora Morgante is a Paediatric Surgeon based in Yorkshire. She obtained her Master’s degree in Medicine and Surgery at ‘Sapienza’ University of Rome (Italy), with the published experimental thesis ‘Vesico-Ureteral Reflux and Renal Function in Patients with Posterior Urethral Valves: a Thirty-Year Analysis’ (Urology, 2011). Subsequently Debora specialised cum laude in Paediatric Surgery with the experimental thesis ‘Paediatric Robotic Pyeloplasty: Learning Curve and Preliminary Outcome’, under the supervision of Prof Denis A. Cozzi (Paediatric Surgery - ‘Sapienza’ University of Rome/Policlinico ‘Umberto I’) and Prof Ramnath Subramaniam (Paediatric Urology – Leeds General Infirmary).
Debora is currently working in the JBU as a Clinical Research Fellow and is registered for a PhD through HYMS. She is supported on a grant from the Medical Technologies Innovation and Knowledge Centre and is supervised by Professor Jenny Southgate and Mr Ramnath Subramaniam (Consultant Paediatric Urologist at Leeds General Infirmary).
Debora is passionate about Paediatric Surgery (with particular interest in Neonatal Surgery and Paediatric Urology) and Basic Science Research (with particular interest in Biomaterials, Tissue Engineering and Regenerative Medicine).
A number of congenital and acquired diseases of the urinary bladder culminate in end-stage disease characterised by small contracted bladders that are susceptible to recurrent infections and create high pressure systems that can cause irreversible damage to the kidneys. Reconstructive surgery in end-stage bladder disease aims to reduce pressures in order to prevent kidney damage. A treatment option is to incise the scar tissue and detrusor muscle of the damaged bladder wall in order to make the inner lining of the bladder (mucosa) bulge. This procedure is known as auto-augmentation or detrusorotomy and can increase bladder capacity and reduce bladder pressures. Because of a high risk of bladder perforation from the procedure, there have been some attempts to cover the bulge with flaps from a variety of vascularised tissues. Debora is testing the possibility of using a novel biomaterial called PABM (porcine acellular bladder matrix), developed previously by the JBU as a tissue-integrative support material for urinary bladder auto-augmentation.
I’m Raphael and I have just started my MSc by Research at the Jack Birch Unit (JBU). I studied BSc Biology at the University of Leeds before pursuing my interest in human genetics and disease by studying MSc Molecular Medicine at the University of York. Since then, I have worked as a research technician at the JBU, aiding in multiple projects that focus on bladder cancer and urothelial development.
Over my time here, I have immersed myself in the ongoing research and gained much lab-based expertise. I will now undertake an MSc by Research where I will focus on a family of proteins called nuclear receptors and their roles in urothelial differentiation. This will provide invaluable information in the context of bladder cancer and also for tissue engineering, where we might manipulate induced pluripotent stem cells in the lab to differentiate into functional urothelium.
I'm a curious engineer who returned to academia in 2020 after two years of wandering in industry. I graduated in 2018 from the University of York with an MEng in Electronics and Computer Engineering. Throughout my ventures, I've worked in several different areas ranging from projects in embedded systems (such as medical or automotive) to mobile applications, chatbots and full-stack.
My PhD is interdisciplinary between Electronics and Biology, and I split my time between the two departments. I am interested in applying ML models to different areas, with a focus on biomedical applications. I am investigating how clustering techniques, together with other ML approaches can improve the bladder cancer sub-typing.
In addition, I've created different visualisation tools that help the JBU members to explore the data. I'm also involved in organising the Introduction to Programming module (Electronics) as a lab leader.