ISTM

2006 - present: Lecturer in Stem Cell Biology, Institute for Science & Technology in Medicine, Keele University Medical School, UK. 
Roles include Chair of Human Tissue Committee and University Biological Safety Advisor.

2004 – 2006: Postdoctoral Fellow in the laboratory of Jim McWhir, Roslin Institute, Roslin, Midlothian, UK
Investigations into effects of hypoxic culture conditions on hESC differentiation, characteristics, and hESC progenitor isolation

2000 - 2004: Postdoctoral Fellow within combined laboratory of Profs Jerry Shay and Woodring Wright, Southwestern Medical Center, University of Texas, USA

1997 - 2000: Full-Time Ph.D Student under supervision of Dr. E. K. Parkinson, CRC Beatson Laboratories, Glasgow, UK
The research within this laboratory was directed towards an understanding of the molecular and genetic events underpinning the development of Squamous Cell Carcinoma of the head and neck.

ISTM Research theme: 1. Bioengineering & Therapeutics

Research interests:

The research within our laboratory is focused on three primary inter-related areas; Basic Biology of Stem Cells; Cellular Response to Physiological Norms; and the Derivation of Clinically Useful Cell Types.

The field of stem cell biology has developed rapidly over the previous 10 years from first descriptions of pluripotent hESC to, more recently, reprogramming mortal somatic cells to pluripotency through the introduction and over-expression of selected genes. Great advances have also been made in the understanding and potential uses of adult derived stem cells.  

In order to facilitate a greater understanding of cellular behavior in response to physiological norms we have begun the process of examining responses of stem cells to physiological levels of oxygen. In normal healthy tissue oxygen tension is substantially lower than atmospheric levels (21% O₂ (147 mm Hg)). Alveoli display a partial pressure of ~110 mm Hg (~15% O₂), arterial blood around 70 mm Hg (~10% O₂), and venous blood around 35 mm Hg (~5% O₂). Mean tissue oxygen tension is also around 35 mm Hg (5% O₂). In many instances it is even lower e.g. brain, kidney, cartilage, fetal, and in many disease states chronically so e.g. infection and cancer.

We have established investigations into the responses of hESC to physiologically (ph) normal oxygen (ox) levels, as determined for pre-implantation blastocyst O₂ exposure levels. These investigations revealed enhanced clonogenicity, reduced chromosomal aberration frequencies, a reduction in cell size and a reduction in cell complexity. These studies have complemented and enhanced similar research studies performed by other pioneering hESC groups. Microarray analysis has now established a ‘phox’ footprint across multiple hESC lines. Ontological analysis of the phox footprint has provided molecular clues to the previous phenotypic observations of reduced cell size and complexity. We are currently complementing this work through examination of hESC proteome response to phox. Future studies are intended to examine specific functions of phox upregulated growth factors, transcription factors, and metabolic agents. Complementary to the above description we are pursuing simultaneous examination of marrow stromal cells at both transcriptional and proteomic levels in phox conditions using our state-of-the-art in-house facilities.

Enhanced understanding of the basic biology of stem cells and the application of phynorm to routine cell culture provides the platform on which we wish to develop the derivation of clinically-useful cells types. It is clear from ongoing research and clinical application that autologous cell therapy is favored at the clinician level while the allogeneic route is favored commercially. We are exploring techniques and methodology to optimize the derivation of cell types related to musculoskeletal disorders. We have recently described the isolation of clonal progenitor cells from hESC-derived Embryoid Bodies. This work represents an important step forward in the realization of the safe application of hESC towards allogeneic cell therapy. The immortality of hESC engenders them well to longitudinal studies and simplifies scale-up of cell numbers. Marrow stromal cells are mortal and senesce after very few passages in culture. We are currently investigating the application of phynorm principles to these and other adult-derived cell types in an effort to enhance cell recovery and expansion while retaining safety.

Journal Publications:

Wimpenny I, Hampson K, Yang Y, Ashammakhi N, Forsyth NR. One step recovery of marrow stromal cells on nanofibers. Tissue Eng Part C Methods 17 Aug 2009.

Forsyth NR, Kay A, Hampson K, Downing A, Talbot R, McWhir J. Transcriptome alterations due to physiological normoxic (2% O2) culture of human embryonic stem cells. Regen Med 3(6):817-833 Nov 2008.

Bullough R, Finnigan T, Kay A, Maffulli N, & Forsyth NR. Tendon repair through stem cell intervention: Cellular and molecular approaches. Disability and Rehabilitation 30(20-22):1746-1751 2008.

Rahman R, Forsyth NR, & Cui W. Telomeric 3'-overhang length is associated with the size of telomeres. Exp Gerontol. 2008 Apr;43(4):258-65. April 2008. Epub Jan 2008.

Tremoleda JL, Forsyth NR, Khan NS, Wojtacha D, Christodoulou I, Tye BJ, Racey SN, Collishaw S, Sottile V, Thomson AJ, Simpson AH, Noble BS, McWhir J. Bone tissue formation from human embryonic stem cells in vivo.Cloning Stem Cells. 2008 Spring;10(1):119-32.

Forsyth NR & McWhir J. Human embryonic stem cell telomere length impacts directly on clonal progenitor isolation frequency. Rejuvenation Res. 2008 Mar;11(1):5-17.

Hewitt Z*, Forsyth NR*, Waterfall M, Wojtacha D, Thomson AJ, McWhir J. Fluorescence-activated single cell sorting of human embryonic stem cells.Cloning Stem Cells. 2006 Fall;8(3):225-34. * These authors contributed equally to this study.

Maida Y, Kyo S, Forsyth NR, Takakura M, Sakaguchi J, Mizumoto Y, Hashimoto M, Nakamura M, Nakao S, Inoue M. Distinct telomere length regulation in premalignant cervical and endometrial lesions: implications for the roles of telomeres in uterine carcinogenesis. J Pathol. 2006 Oct;210(2):214-23.

Forsyth NR, Musio A, Vezzoni P, Simpson AH, Noble BS, McWhir J. Physiologic oxygen enhances human embryonic stem cell clonal recovery and reduces chromosomal abnormalities. Cloning Stem Cells. 2006;8(1):16-23.

Forsyth NR, Elder FF, Shay JW, Wright WE. Lagomorphs (rabbits, pikas and hares) do not use telomere-directed replicative aging in vitro. Mech Ageing Dev. 2005 Jun-Jul;126(6-7):685-91.

Forsyth NR, Morales CP, Damle S, Boman B, Wright WE, Kopelovich L, Shay JW. Spontaneous immortalization of clinically normal colon-derived fibroblasts from a familial adenomatous polyposis patient. Neoplasia. 2004 May-Jun;6(3):258-65.

Walter M, Forsyth NR, Wright WE, Shay JW, Roth MG. The establishment of telomerase-immortalized Tangier disease cell lines indicates the existence of an apolipoprotein A-I-inducible but ABCA1-independent cholesterol efflux pathway. J Biol Chem. 2004 May 14;279(20):20866-73. Epub 2004 Mar 4.

Forsyth NR, Evans AP, Shay JW, Wright WE. Developmental differences in the immortalization of lung fibroblasts by telomerase. Aging Cell. 2003 Oct;2(5):235-43.

Bryce SD, Morrison V, Craig NJ, Forsyth NR, Fitzsimmons SA, Ireland H, Cuthbert AP, Newbold RF, Parkinson EK. A mortality gene(s) for the human adenocarcinoma line HeLa maps to a 130-kb region of human chromosome 4q22-q23. Neoplasia. 2002 Nov-Dec;4(6):544-50.

Forsyth NR, Morrison V, Craig NJ, Fitzsimmons SA, Barr NI, Ireland H, Gordon KE, Dowen S, Cuthbert AP, Newbold RF, Bryce SD, Parkinson EK. Functional evidence for a squamous cell carcinoma mortality gene(s) on human chromosome 4. Oncogene. 2002 Aug 1;21(33):5135-47.

Forsyth NR, Wright WE, Shay JW. Telomerase and differentiation in multicellular organisms: turn it off, turn it on, and turn it off again. Differentiation. 2002 Jan;69(4-5):188-97. Review.

Parkinson EK, Munro J, Steeghs K, Morrison V, Ireland H, Forsyth N, Fitzsimmons S, Bryce S. Replicative senescence as a barrier to human cancer. Biochem Soc Trans. 2000 Feb;28(2):226-33.

Bryce SD, Forsyth NR, Fitzsimmons SA, Clark LJ, Bertram MJ, Cuthbert AP, Newbold RF, Pereira-Smith OM, Parkinson EK. Genetic and functional analyses exclude mortality factor 4 (MORF4) as a keratinocyte senescence gene.Cancer Res. 1999 May 1;59(9):2038-40.

Book Chapters:

Tendon Tissue Engineering. Hampson K., Forsyth N.R., El Haj A. and N. Maffulli. In Topics in Tissue Engineering Vol 4 (2008).

M.Sc. Cell & Tissue Engineering (ISTM, Keele University).

Module Coordinator (Sept 2006 – present) – ‘Stem Cell Therapy’.

This course comprises 10 lectures covering all aspects of stem cells and their application to regenerative medicine. My duties include organizing course content, inviting speakers, delivering lectures, and developing practical assessments. Devise and mark exam.

Module Coordinator (Sept 2006 – present) – ‘Molecular Techniques’.

This course comprises a series of lectures covering all aspects of molecular techniques and their applications. My duties include organizing course content, inviting speakers, delivering lectures, and developing practical assessments. Devise and mark exam.

Problem-Based Learning Year 1 Tutor. (Keele University Medical School).

Research Funding:

Innovation Keele Development Fund

£25,000 March 2008 ‘Prototype Development Award’.

£25,000 March 2008 ‘Stem Cell Strategies for the Treatment of Pulmonary Fibrosis and Fibrotic Lung Disorders’. (Joint award with Professor Monica Spiteri).

American Orthopaedic Foot and Ankle Society – Research Grant

£5,000 March 2008 ‘Can human bone marrow-derived stem cells differentiate into tendon-forming cells?’ (Joint award with Professor Nicola Maffulli).

British Orthopaedic Foot and Ankle Society – Research Grant

£5,000 January 2008 ‘Can bone marrow derived stem cells differentiate into tendon forming cells?’

Royal Society – Conference Grant

£1,400 January 2008 - funded attendance at Keystone Hypoxia Symposium, Vancouver, Canada.

Keele University – Postdoctoral Scientist

£70,000 June 2007

Mercia Spinner Award – Prototype Development Award

£15,000 April 2007

Keele University – Phd Student

£80,000 November 2006

Genomia Fund – Research Grant

£32,000 May 2006.

Current Research Team Members:

Dr Karen Hampson – Postdoctoral Research Scientist. August 2007 – present. ‘Strategies to direct differentiation of human stem cells in tendon’.

Mr Alasdair Kay – PhD Student. November 2006 – present. ‘Optimization of recovery and expansion conditions for clinically useful cell types’.

Future Research Team Members:

Dr Amiq Gazdhar – European Respiratory Society Fellow. April 2008 – March 2009. ‘Identification of secreted factors which promote lung wound healing and reverse fibrotic scarring’. (Joint supervision with Professor Monica Spiteri.)

Mr Karl Davis – Fourth Year Medical Student Placement (Keele University Medical School). May 2008 – August 2008. ‘Defining oxygen and glucose requirements of human embryonic stem cells’.

Mr Faye Stockton - Fourth Year Medical Student Placement (Keele University Medical School). May 2008 – August 2008. ‘Deriving tenocytes from human stem cells.’ (Joint supervision with Professor Nicola Maffulli and Dr Karen Hampson.)

Mr Harnoor Bamrah - MSc Biotechnology (University of Abertay Dundee). April 2008 – September 2008. ‘Defining tendogenic stimuli for human mesenchymal stem cells in vitro’. (Joint supervision with Dr Karen Hampson.)

Mr Param Cheema - MSc Biotechnology (University of Abertay Dundee). April 2008 – September 2008. ‘Defining Oxygen and Glucose Requirements of Human Embryonic Stem Cells’.

Dr Musansar Latif - MSc Biotechnology (University of Abertay Dundee). April 2008 – September 2008. ‘An investigation into the synergistic effects of TGF-B1 and FGF2 on MSC chondrogenesis’. (Joint supervision with Mr Alasdair Kay.)

Previous Research Team Members:

Mr Howard Banks – Third year Undergraduate Life Science Project Placement (Keele University). October 2007 – March 2008. ‘Bioinformatic Comparison of Embryonic and Mesenchymal Stem Cells’.

Mr Liam Kilbane - Third year Undergraduate Life Science Project Placement (Keele University). October 2007 – March 2008. ‘Bioinformatic analysis of ESCs and MSCs to determine suitability for tendon repair.’

Ms Manjusha Sala – MSc Biotechnology (University of Abertay Dundee). April 2007 – September 2007. ‘Bioinformatic Determination of Stem Cell Applicability to Tendon Repair’.