Tuesday 16 December 2014

Hepatocytes and Antioxidant Screening and Osteoarthritis Susceptibility



Institute Research Student Seminars

Speakers:  Emily Hudson & Katherine Johnson


Venue: Seminar room L2.5, 2nd floor, William Leech Building, Medical School

Date and time:  Wednesday 17th December 2014 at 12.30


Emily Hudson will present:


“Derivation of human hepatocytes from pancreatic progenitor cells and their use in a novel antioxidant screening platform”

(Diagnostic and Therapeutic Technology Group)


Primary hepatocytes are considered an ideal cell model for the study of hepatotoxicity, however they’re difficult to culture in vitro as they resist proliferation.  While there are a large variety of other models used to investigate liver toxicity there is yet to be a fully competent model that can be produced in required to meet demand.  A possible solution to this problem is the conversion of pancreatic cells to hepatocytes using steroid treatment.  This has already been shown to be viable in rodent cells with the creation of the B13/H cell line, derived from the B13 cell line.  When tested, if these B13/H cells respond to hepatotoxins in the same way as hepatocytes it could provide the rationale for expanding the research into a human cell line and ultimately generate a cell line for use in regulatory toxicology studies, disease modelling.



Key words: Reactive Oxygen Species, Hepatocytes, Nanosensors


Katherine Johnson will speak on:


Functional analysis of the osteoarthritis susceptibility locus marked by the polymorphism rs10492367”

(John Loughlin: Musculoskeletal Research)


The 2012 arcOGEN genome-wide association study reported that the rs10492367 G to T single nucleotide polymorphism (SNP) marks a region on chromosome 12p that is associated with hip osteoarthritis (OA) in Europeans. To functionally dissect this region, we i) investigated differential transcription factor binding, ii) quantified expression of nearby genes and iii) analysed methylation levels across the region.



Keywords: Osteoarthritis, functional analysis, methylation



Chair:  Sophie Cassidy







Thursday 11 December 2014

Differentiation, Invasion, Fibroblasts, Myofibroblasts, Keratinocytes, Human Papillomavirus (HPV), Retinoblastoma

Newcastle University Research Fellowship Candidate Seminar


Speaker: Dr Adam Pickard, Centre for Cancer Research and Cell Biology, Queen's University Belfast


Venue: Lecture Theatre E, Dental School

Date and Time: 15th December 2014 11.00-12.00


Dr Pickard will present: '' Stromal control of epithelial differentiation and cancer invasion – a role for the retinoblastoma protein, pRb''



The retinoblastoma proteins (Rb) is a key regulator of cell division and also epithelium differentiation. Animal studies have demonstrated that Rb can regulate the growth and differentiation of neighbouring cells, and this has been explored further using a three-dimensional organotypic culture system.  Depletion or inactivation of Rb in primary human fibroblasts, disrupts the differentiation of the neighbouring epithelium, through altered secretion of the keratinocyte growth factor (KGF).  Phosphorylation (inactivation) of Rb, has been identified in the stromal compartment of human tumours (Head and Neck cancers), specifically within the FSP1-positive population of fibroblasts. Rb inactivation promotes invasion of a cancerous epithelium with KGF driving expression of MMP1. Myofibroblasts, a sub-population of fibroblasts often associated with poor –disease outcome, also promote epithelium invasion,  therefore the role of Rb in myofibroblast differentiation was examined. Rb is degraded by the proteasome during TGFβ mediated differentiation, and Rb-depleted fibroblasts behave as myofibroblasts in collagen contraction assays. Both cell types produce higher levels of EGF which alone promotes epithelial invasion through inducing an epithelial to mesenchymal-transition.  Low doses of the EGFR targeted therapies efficiently inhibit the invasion process mediated by myofibroblasts, myofibroblasts are postulated as a marker of prognosis or therapeutic response.



Differentiation, Invasion, Fibroblasts, Myofibroblasts, Keratinocytes, Human Papillomavirus (HPV), Retinoblastoma


Chair: Professor John Isaacs


Wednesday 10 December 2014

Dendritic cells, DNA methylation, and noncoding RNAs - Arthritis Research

The MRG Lab Meeting will be taking place on Friday 12th December 2014 at 9.00am in the Baddiley Clark Seminar Room.




Carole Proctor




Faye Cooles (Clinical Research Fellow – PIs Cat Hilkens/John Isaacs) Title of Talk – "Plasmacytoid dendritic cells subsets in RA and SLE"


Ruddy Gomez (Research Associate - PI David Young) Title of Talk – "Analysis of DNA methylation helps to identify key TXFs  during MSC differentiation "


Matt Barter (Research Associate - PI David Young) Title of Talk – "Long noncoding RNAs in chondrocyte development and cartilage "




“A novel defect in the IFN alpha signalling pathway”




Institute Research Student Seminars

Speakers:  Siti Mohamad & Eleana Pappa


Venue: Seminar room L2.5, 2nd floor, William Leech Building, Medical School

Date and time:  Wednesday 10th December 2014 at 12.30


Siti Mohamad will present:


"A novel defect in the IFN alpha signalling pathway"

(Sophie Hambleton: Primary Immunodeficiency Group)


IFN alpha signalling is responsible for protecting the body against viruses. We found a novel defect in the IFN alpha signalling pathway in a patient with a severe disseminated MMR vaccine.


Key words: Viral susceptibility, IFN alpha signalling, novel defect


Eleana Pappa will discuss:


"Transcriptional and Phenotypic Characterization of Hepatic Stellate Cells"

(Derek Mann: Fibrosis Group)


Correlation of liver stiffness with fibrosis progression has been observed in many liver diseases. Hepatic stellate cells (HSC) are the main scaring forming cells in liver fibrosis. Activation of HSC from quiescent to myofibroblasts is the initial step for fibrosis development. In this project we evaluate the importance of substrate stiffness as driving force for HSC activation.


Key words: Liver fibrosis, Hydrogels, HSC 


Chair:  Kile Green







Tuesday 9 December 2014

Translational Genomics of Rare Diseases and Cancer

Research Day
Thursday 11 December 2014
Great North Museum 9:30 - 18:00

Including 10:00-10:30 Professor Mike Briggs – Common therapeutic targets in genetic skeletal diseases

Institute Christmas Coffee Morning











































Jenna Ho

PA to:

Professor John Isaacs, Director of the Institute of Cellular Medicine

Professor Neil Sheerin, Professor of Nephrology

4th Floor William Leech Building

Medical School

Newcastle University

Framlington Place

Newcastle Upon Tyne



Tel: 0191 208 6227

Fax: 0191 208 5066


Email: jenna.ho@newcastle.ac.uk

Web:    http://www.ncl.ac.uk/


Human tissue mononuclear phagocyte systems 12pm Lecture Theatre E, Dental School


Speaker: Dr Muzz Haniffa, Institute of Cellular Medicine


Venue: Lecture Theatre E, Dental School

Date and Time: Tuesday 9th December at 12-1300



Dr Haniffa will present:

''Human tissue mononuclear phagocyte systems revisited''



Dendritic cells (DCs), monocytes and macrophages are a heterogeneous population of mononuclear cells that are specialized in antigen processing and presentation to initiate and regulate immune responses. There has been a paradigm shift in our understanding of mononuclear phagocytes beyond the traditional view of DCs and macrophages as derivatives of monocytes.

While harnessing DCs and macrophages for therapeutic purposes has major implications for infection, vaccine science, transplantation, tolerance induction, inflammation and cancer immunotherapy, the use of monocyte-derived cells in therapy has so far been underwhelming.  This is due to our incomplete understanding of human mononuclear phagocyte biology.


In this seminar, I will present our current understanding of the human mononuclear phagocyte network, illustrate the origin and functional differences between DCs and macrophages, demonstrate the utility of comparative biology analysis to identify the homologous cell populations in human and mouse and how this approach has been instrumental in unraveling the complexity of mononuclear phagocyte heterogeneity in both species.     


Chair: Dr Alison Tyson -Capper



Wednesday 3 December 2014

Cartilage Homeostatis 8th December 2014 10.30am


Speaker: Dr Kazuhiro Yamamoto, Kennedy Institute of Rheumatology, University of Oxford

Newcastle University Research Fellowship Candidate


Venue: L.2.2 2nd Floor William Leech Building

Date and time: Monday 8th December 2014 10.30-11.30am


‘’Regulation of Cartilage Homeostatis by Endocytic Pathways in Health and Disease’’


Cartilage degradation in osteoarthritis (OA) is now well established to be the result of elevated proteinase activities, with the key enzymes being aggrecanases and collagenases. Their activities are not readily detected in normal cartilage, but they are greatly upregulated under pathological conditions, such as rheumatoid arthritis (RA) and OA, at the levels of transcription, epigenetic modification, posttranscriptional regulation by microRNAs, activation of pro-enzymes and inhibition by endogenous inhibitors. Recently, I have discovered an additional regulatory mechanism in that many of the key matrix-degrading metalloproteinases are rapidly endocytosed and degraded by chondrocytes in healthy cartilage, and this process is mediated by the endocytic receptor, low-density lipoprotein receptor-related protein 1 (LRP1) on the cell surface. However, under inflammatory conditions, or in OA cartilage, the LRP1 is proteolytically shed from the cell surface, which impairs the endocytic pathway. This introduces further complexity to extracellular matrix (ECM) catabolism in health and disease. I’m currently investigating how alterations in endocytosis affects cartilage homeostasis and what are the molecular events associated with it. A clearer understanding of this important mechanism will reveal novel biomarkers and generate new therapeutic approaches for OA, a disease that currently has no disease-modifying drugs. This unmet clinical need represents the major area of research to identify treatable therapeutic targets as our population ages.

In this seminar, I will talk about my current and future approaches to investigate how normal adult cartilage maintains homeostasis by regulating its ECM turnover and how this balance is lost upon ageing and in pathological conditions. I will also talk about a potential of my entirely novel approach to understand tissue catabolism in other tissue contexts and diseases.


Key words: Tissue catabolism; Osteoarthrits; Endocytosis; Extracellular trafficking; Metalloproteinases.