Background

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.

Interests

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.

Background

Simon did both his graduate BSc degree and PhD at the University of York. He has previously held a Yorkshire Enterprise Fellowship and a Royal Society of Edinburgh/BBSRC Enterprise Fellowship. As an Enterprise Fellow, Simon spent a proportion of his time exploring the commercial potential of the Jack Birch Unit’s research. In 2010, Simon and Prof Southgate won the $300,000 Astellas European Foundation Urology Prize which is being used to examine the urothelial transcriptome in order to define the “Urotheliome”.

Interests

Simon is a cell biologist with interdisciplinary skills in the fields of cell signalling and tissue engineering. His research has focused on promoting differentiated tissue function in vitro using ligand-driven and biomaterial-guided approaches.

Simon was awarded the Wellcome VIP Fellowship from the Biology Department at the University of York in 2011.

He currently works on the following JBU commercial output:

1) Histotech – offering customised contract histology and immunohistology services focused on dealing with the specific problems associated with analysing biomaterial-supported tissues.

Background

Claire has been a post-doctoral research scientist in the Jack Birch Unit since 2001 and is currently funded by Yorkshire Kidney Research Fund. She was previously based in Manchester, where she worked on hepatocyte de-differentiation.

Research interests

When urothelial cells are grown in culture, they become highly proliferative and lose expression of differentiation-associated genes, such as the uroplakins. Claire has been involved in identifying the pathways involved in controlling proliferation and differentiation in normal human urothelial (NHU) cells. She has shown that urothelial proliferation is mediated through an autocrine loop involving the epidermal growth factor receptor and that when this receptor is blocked, terminal differentiation can be induced by agonists that activate the PPARγ nuclear receptor.

Claire is currently funded by Yorkshire Kidney Research Fund to investigate innate immunity of the urothelium in response to uropathogenic bacteria that cause urinary tract infections. This work is focused on the role of the toll like receptors.

Background

Zac did a PhD in Liverpool working on smooth muscle contraction, before completing a Smith & Nephew funded post-doc in York. He moved to an industry-funded post-doc at the University of Bradford, before returning to York to work on the EPSRC funded Epitheliome project.

Zac is currently working as a named researcher on a three year Wellcome Trust-funded grant to model calcium signalling. This is a collaboration with computational biologists at the University of Sheffield, including Dr Dawn Walker, and Dr Peter Appleby.

Research interests

Current interests include the role of calcium signalling in non-differentiated and differentiated urothelium. We have shown that injury to a confluent urothelial cell monolayer results in the initiation and propagation of a calcium wave and that this calcium signal is involved in directing cell behaviour.

Other interests include investigating the function of the RhoA/Rho-kinase pathway in urothelial wound healing. The migration of the cells at the wound edge is known to be important in wound closure and we have shown that inhibition of Rho kinase results in inhibition of wound healing in differentiated cultures, whilst accelerating wound closure in non-differentiated cultures.

Background

Henry graduated from medical school at Liverpool University in 2005, having also intercalated to obtain a Pharmacology BSc with Honours. During this period he developed an interest in research, undertaking his dissertation on the subject of “Rational Combined Chemotherapy” at the Henry Wellcome Laboratory in Liverpool. Having qualified, he began his surgical training at the Leeds Teaching Hospitals, and has pursued his training as a career urologist, whilst maintaining a keen interest in research and academic medicine.

Research Interests

Ketamine is well known for its use as an anaesthetic agent in both humans and animals, but in recent years has also become popular with drug abusers. Regular ketamine use can cause damage to the lining of the bladder, resulting in significant urinary symptoms that can be very difficult to treat. The mechanism by which damage to the urinary tract occurs is poorly understood.

Henry’s research uses established in vitro methods with normal human urothelial cell cultures to identify potential mechanisms of ketamine interaction with urothelium and gain insight into the clinical relevance of any observations by examining specimens of ketamine-induced cystitis.

Background

Sam obtained a BSc in Molecular Cell Biology from the University of York and is currently studying for a PhD supported by a BBSRC CASE studentship with Tissue Regenix. He is supervised by Professor Jenny Southgate, Professor Eileen Ingham (University of Leeds) and Dr Helen Berry (Tissue Regenix).

Interests

The extracellular matrix (ECM) can be harvested from a variety of tissues and used as a natural biological scaffold in regenerative medicine and tissue engineering strategies. In vivo data implicates the macrophage as responsible for mediating the host response to such biomaterials and hence for determining the fate of the implant.

Although a spectrum of macrophage phenotypes from pro-inflammatory to alternative activation are recognised, the rules that govern the macrophage response to biological scaffolds are not well defined. Sam is attempting to study the scaffold-macrophage interactions and consequent remodelling events in cell culture in the expectation that this will help understand macrophage response to biological scaffolds and be useful as an initial indicator of biocompatibility in vivo.

In the future, the remodelling properties of macrophages could be harnessed to promoted cellular infiltration of biological and synthetic scaffolds in order to produce functional tissue constructs.

Background

Carl has a BSc from Salford University and an MSc in Bioscience Technology from The University of York. Currently, Carl is studying for a PhD supported by a BBSRC CASE studentship with GlaxoSmithKline. He is supervised by Professor Jenny Southgate, Professor Jane Thomas-Oates (Department of Chemistry) and Dr Andy Nicholls (GlaxoSmithKline).

Interests

Mechanisms that control heritability and modulation of epigenetic markers remain unclear. Genome mapping of transcriptomic data has shown deregulation of a number of contiguous regions of chromosomes in bladder cancer, potentially as a consequence of long range epigenetic events which may lead to aberrant cell behaviour.

Urothelium is normally a highly quiescent epithelial population, but has a unique wound healing response during which the cells are able to rapidly re-enter the cell cycle and adopt a proliferative phenotype. Carl’s interests are investigating epigenetic modulation of chromatin during urothelial differentiation by utilising established methods of urothelial cell culture to produce in vitro populations of regenerating and differentiated cells. Mass spectrometry-based proteomics and chromatin immunoprecipitation are being used to study known and predicted epigenetic modifiers in order to assess their effects on proliferation and differentiation.

Background

Andrew graduated from Sheffield University with a MChem Hons in September 2008 before starting as a PhD student on the Tissue Engineering and Regenerative Medicine Doctoral Training College (DTC TERM) programme http://www.dtcterm.leeds.ac.uk/programme/joint.shtml. He is currently based in the Polymer and Biomaterials Chemistry laboratories in Sheffield and is supervised by Professor Steve Rimmer (University of Sheffield) with co-supervision by Professor Jenny Southgate and Professor Eileen Ingham (University of Leeds).

Interests

Andrew is developing and systematically testing the properties of a range of methacrylate-based hydrogels as potential biomaterials. The properties being investigated include physical properties (swelling and water content), porosity, modulus (stiffness), roughness, chemistry (addition of functional co-monomers) and biochemistry through inclusion of Arg-Gly-Asp (RGD) groups by coupling to activated esters).

Altering and examining the properties of the hydrogel networks will give insight into how contact with biomaterials could influence the development of pro-inflammatory or alternatively-activated macrophage phenotypes. The ultimate goal is to tailor biomaterial properties to harness the alternatively-activated phenotype in macrophages, leading to increased regenerative activity and a reduced inflammatory response in vivo.

Background

Jenny joined the group in January 2004 after obtaining a BSc in Cell Biology from Durham University. 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. In 2008 Jenny enrolled in a part-time Masters of Philosophy degree.

Interests

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.

Background

Lisa graduated from the University of Essex in 2001 with a BSc and MSc in Biology. She then spent a number of years working in industry, before joining the Jack Birch Unit in 2005 as a research technician providing molecular biology support. Lisa enrolled as a full time PhD student in August 2007 under the supervision of Professor Jenny Southgate and Dr Nik Georgopoulos, with funding from York Against Cancer (YAC).

Interests

Lisa has just finished her PhD studies looking at the role of Wnt signalling in urothelial regeneration.

Background

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.

Interests

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. 

Background

Marie joined the Jack Birch Unit in October 2008 having previously worked at Imperial College in London.

Interests

Marie provides secretarial support to Professor Southgate and looks after the administrative needs of the Jack Birch Unit. She provides the main contact point for the JBU. Marie also provides administrative support for Histotech.

Background

Ruth joined the Jack Birch Unit in July 2005 having previously worked at the ICRF Cancer Medicine Research group at St James's University Hospital, Leeds where she obtained her MPhil.

Interests

Ruth provides technical support to all members of the research group.

Background

Amy studied at the University of Otago, New Zealand were she gained a BSc (Hons) in Anatomy and a PhD in Reproductive Biology.   She has since completed post-doctoral projects into prognostic gene signatures in human melanoma, the role of alveolar macrophages in homeostasis and infection, and the commercial use of DNA as a molecular marker. 

Interests

Amy joined in 2011 and currently works on the following JBU commercial output:

1) Histotech – offering customised contract histology and immunohistology services focused on dealing with the specific problems associated with analysing biomaterial-supported tissues.

Background

Lucinda obtained a BSc in Biochemistry from the University of York and is currently studying for a PhD funded by York Against Cancer (YAC). She is supervised by Professor Jenny Southgate.

Interests

Non-genotoxic carcinogenesis and epigenetic deregulation in human bladder epithelial cells

The urothelium is exposed to urinary excreted carcinogens from environmental, occupational and dietary sources. These carcinogens include heavy metal compounds such as arsenic, nickel and cadmium. Carcinogenic metals are typically weak mutagens; this suggests that genetic mechanisms are not responsible for metal-induced carcinogenesis. Non-genotoxic carcinogenesis is relatively poorly understood, however recent advancements show that epigenetic dysregulation of gene expression may play an important role.

Lucinda is using established urothelial cell culture methods to investigate non-genotoxic epithelial carcinogenesis. Heavy metals and epigenetic modifiers are being used to assess their effects on proliferating and differentiated normal human urothelial cells in order to determine the role that epigenetic dysregulation plays in non-genotoxic epithelial carcinogenesis.

Background

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. 

Interests

Jo provides molecular biology support to all members of the group.

Background

Edward graduated with a BSc in Pharmacology from the University of Leeds in 2010 and gained an MRes in Pharmaceutical and Biomedical Science from the University of Brighton in 2011. He is currently studying for a PhD supported by a BBSRC CASE studentship with Syngenta, supervised by Professor Jenny Southgate and Paul Rawlinson (Syngenta).

Interests

Extrapolating from experimental to human studies via the in vitro paradigm

Urothelial cells are exposed to drugs, pesticides and other chemicals excreted in urine that can cause pathological conditions such as cystitis and bladder cancer. Toxicology studies in rodents are designed to predict the risk posed to humans by such chemicals, however the results of these studies are not always relevant to humans. Deficiencies in the rodent models used can lead to toxic chemicals being licenced for use and safe chemicals being withdrawn from production. A human urothelial cell culture system has been developed that has the potential to be used during the early stages of drug and chemical development to predict bladder toxicity. Before it is able to be incorporated into chemical toxicity studies, this urothelial system requires careful validation to ensure that it is fit for purpose. If successful it will reduce the attrition rate of chemicals during discovery and development, improve safety standards and reduce the number of in vivo studies that take place.

Background

Interests