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The University of Southampton
Biological Sciences
Phone:
(023) 8059 4273
Email:
C.E.Clarkin@soton.ac.uk

Dr Claire E Clarkin BSc

Associate Professor in Developmental and Skeletal Biology

Dr Claire E Clarkin's photo

Claire is Associate Professor in Developmental and Skeletal Biology, she leads the Developmental Biology Theme within Biological Sciences (Faculty of Environmental and Life Sciences), and she is part of the Centre for Human Development, Stem Cells and Regeneration (Medicine). She has specific interest in how blood vessels interact with tissues and organs during development, adulthood and disease. To date much of her research has focused on the musculoskeletal system and how with age, unhealthy blood vessels can influence progression of degenerative bone diseases. In addition, she is also focussed on targeting the blood supply to improve fracture repair outcomes and orthopaedic implant longevity.

 

The blood supply to bone is critical for development and is also linked to disease. However, research into this area has been challenging as the vasculature is deeply buried within the bone mineral. To address this, I work closely with engineers, physicists and clinicians and develop new methods to better address the ongoing questions surrounding the regulation of the vasculature in bone.

Career History

2017-present: Associate Professor in Developmental and Skeletal Biology. University of Southampton, UK.
2011-2017: Lecturer in Developmental Biology. University of Southampton, UK.
2008-2011: Diabetes Foundation/Diabetes UK Research Fellow. King’s College, London, UK.
2005-2008: Postdoctoral Research Associate (Arthritis Research UK): Department of Veterinary Basic Science, The Royal Veterinary College, London, UK.

Academic Qualifications

2002-2005: PhD (BBSRC). The Royal Veterinary College, London, UK.

Image courtesy of Juan Nunez
Vascular canal networks (red) and osteocyte lacunae (yellow)

Imaging blood vessels in bone

Utilising high resolution computed tomography to visualise vascular canals in cortical bone (Claire Clarkin, Philipp Schneider and Philipp Thurner)

Micro-computed tomography (μCT) provides a 3D and non-destructive imaging technique for bone and the capabilities of standard μCT can be significantly extended when synchrotron X-ray sources are used, achieving higher spatial resolutions to resolve porosity present in cortical bone within a few minutes such as the vascular canal networks (in red) and osteocyte lacunae (in yellow). Images courtesy of Juan Nunez.

Detection of intracortical blood vessels without contrast agents using propagation-based phase contrast-enhanced imaging (Claire Clarkin, Philipp Schneider and Philipp Thurner)

Claire's laboratory has shown that propagation-based phase contrast-enhanced tomography can be used to resolve soft tissue comprising blood vessel details in  bone, when an appropriate propagation distance is chosen. This technique allows for simultaneous visualisation of the cortical bone microstructure including osteocyte lacunae and canal networks alongside the blood vessels themselves. Image, below right, courtesy of Juan Nunez. 

Image courtesy of Juan Nunez
3D reconstruction of blood vessel within intracortical canal

Using Raman Spectroscopy and Second Harmonic Generation to study osteogenesis (Claire Clarkin, Sumeet Mahajan and Richard Oreffo)

Raman spectroscopy, a label free technique, has proved to be a useful tool for detecting early biochemical changes in cells. Utilising these techniques we have characterised specific molecular signatures of primary bone forming osteoblasts at distinct stages of osteogenic differentiation and in whole bone sections.

Changes in collagen structure is a well-known indicator of bone disease. Using Second Harmonic Generation (SHG), a non-linear imaging technique, it is possible to investigate changes in collagen fibre directionality, length and width to pinpoint specific changes to bone integrity in a variety of developmental and diseased models.

SHG can also  be used for early detection of collagen type I formation in culturing osteoblasts. Over time the fibres develop and become more ordered as mineralisation occurs. SHG (cyan) can be used to image the collagen fibrils as shown below (primary osteoblasts cultured for 3, 5, 7, 14 days (left to right)). Images courtesy of Stephanie Smith.

Images courtesy of Stephanie Smith
Primary osteoblasts cultured for 3, 5, 7 and 14 days

Regulation of Vascular Endothelial Growth Factor (VEGF) in Bone

Bone is a dynamic tissue that is constantly renewed throughout life; Claires research thus far indicates that bone-forming osteoblast cells are a significant source of blood vessel-attracting factors in bone (VEGF) and her long term research aims to identify new drug targets that will permit selective control of bone’s blood supply to allow sufficient support for the process of bone renewal.  Claires laboratory in Southampton has unique models in place to dissect the directionality of signalling which exists between bone cells and endothelial cells.

This project has received PhD funding from Arthritis Research UK (Alice Goring) and currently is in collaboration with Professor Bjorn Olsen (Harvard School of Dental Medicine), Professor Philipp Thurner (Tuwien, Vienna), Professor Alan Boyde (Queen Mary’s London), Professor Andrew Pitsillides (Royal Veterinary College London), Professor Richard Oreffo (Medicine, Southampton), Professor Phillip Schneider (Faculty of Engineering and Physical Sciences, Southampton) and Mr Doug Dunlop (Medicine, Southampton).

Modulating biomechanics and blood supply to improve bone strength in Pagets disease

Paget’s disease of bone (PDB) is the second most common bone disease after osteoporosis. Excessive formation of weak and brittle bone results from PDB. Like osteoporosis, fracture is also a well-recognised complication of PDB and early diagnosis is key to treatment, but remains difficult. 3D-imaging tools such as computed tomography and Finite Element analyses are currently being looked into to predict stresses throughout bone. Within this project, Pagetic bones will be analysed using these 3D-imaging tools to provide information about the bone structure/shape improving our understanding for the role of blood vessels in this disease. This project has received funding from Paget's Association, HEIF and the Institute for Life Sciences (PhD, Alisha Sharma) and is in collaboration with Professor Stuart Ralston (University of Edinburgh), Dr Christian Klein (Roche, Zurich), Dr Bram Sengers (Faculty of Engineering and Physical Sciences, Southampton) and Dr Philipp Schneider (Faculty of Engineering and Physical Sciences, Southampton). Images courtesy of Dr Bram Sengers.

Images courtesy of Dr Bram Sengers
3D based finite element models of bone microstructure

Optimising shoulder replacement by improving local angiogenesis

Decreased bone mass and deficient osteogenesis have been linked to inadequate vascular supply or inappropriate bone vascularity, endorsing a central role for the vasculature in bone formation. It remains undefined, however, whether primary control of bone angiogenesis might assist with long term fixation of glenoid and humeral components during shoulder replacements. This project examines the behaviour of bone forming osteoblasts derived from specific cortical, subchondral and trabecular bone regions and aims to define whether they exhibit distinct potential for driving osteogenesis and angiogenesis. This project has received funding from by Orthopaedic Research UK, Mathys Orthopaedic (PhD, Stephanie Marfy-Smith), DOT Implant solutions (PhD Aikta Sharma) and is in collaboration with Professor Andrew Pitsillides (Royal Veterinary College), Professor Roger Emery (Imperial College, London), Professor Richard Oreffo (Medicine, Southampton) and Professor Sumeet Mahajan (Chemistry, Southampton).

Research group

Biomedical Sciences

Affiliate research group

Institute for Life Sciences (IfLS)

Research project(s)

Elucidating the role of vascular endothelial growth factor in regulating adult bone health, strength and repair

This project looks at the role of VEGF on bone homeostasis, with a particular focus on the vasculature.

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Articles

Conferences

Sharma A, Emery R, Pitsillides AA, Oreffo ROC, Mahajan S, Clarkin CE (2019) Molecular imaging modalities reveal pathological matrix disorganisation in whole bone sections and isolated osteoblasts. Oral presentation. New Investigator Award. Bone Research Society and British Orthopaedic Research Society joint annual meeting, Cardiff, 3-6th September.

Sharma AC, Ralston S, Sengers B, Schneider P, Clarkin CE (2019) Sexual dimorphism in both bone geometry and bone strength for a mouse model of Paget's disease of bone. Oral presentation. Submitted to Bone Research Society and British Orthopaedic Research Society joint annual meeting, Cardiff, 3-6th September.

Goring A, Ferrara N, Olsen BR, Hesse E, Oreffo R, Schneider P, Clarkin CE (2019) Do sex hormones determine sexual dimorphism of the bone vasculature. Oral poster presentation. Submitted to Bone Research Society and British Orthopaedic Research Society joint annual meeting, Cardiff, 3-6th September.

Sharma A, Emery R, Pitsillides AA, Oreffo ROC, Mahajan S, Clarkin CE (2019) Raman spectroscopy reveals phosphate signatures in osteoblasts which associate distinctly with cell viability and differentiation. Oral and poster presentation, Herbert Fleisch Workshop, International Federation of mineral research, Brugge, Czech Rep, March 2019.

Sharma AC, Ralston S, Sengers B, Schneider P, Clarkin CE (2019) Could bone shape predict fracture risk in Pagets disease of bone? Poster presentation, Herbert Fleisch Workshop, International Federation of mineral research, Brugge, Czech Rep, March 2019

Sharma A, Goring A, Emery R, Olsen BR, Pitsillides AA, Oreffo ROC, Mahajan S, Clarkin CE (2019) Raman spectroscopy and second harmonic generation imaging reveal sexually dimorphic influence of osteoblast-derived VEGF on bone mineral and matrix composition. Oral and poster presentation at British Society of Matrix Biology, Liverpool April 2019.

Goring A, Ferrara N, Olsen BR, Hesse E, Oreffo R, Schneider P, Clarkin CE (2018) Increased sclerostin expression following OB-derived VEGF deletion. Oral presentation. Bone Research Society Annual meeting Winchester 27-29th June. New Investigator Award. Best oral presentation prize.

Behzad Goring A, Ferrara N, Olsen BR, Hesse E, Oreffo R, Schneider P, Pitsillides AA Clarkin CE (2018) VEGF exerts sexually dimorphic effects on bone mass and architecture. Oral poster presentation. Bone Research Society Annual meeting Winchester 27-29th June.

Nunez J, Goring A, Thurner P, Schneider P * and Clarkin CE (2018) A model to study the role of the vasculature and vascular-specific mediators with ageing for degenerative bone diseases. Oral presentation. 8th World Congress of Biomechanics, 8-12th July Dublin. (*presenting author)

Goring A Boyde A Ferrara N, Olsen BR, Hesse E, Oreffo R, Schneider P, Clarkin CE (2018) Osteoblast-specific VEGF deletion reveals a paracrine role for endothelial-derived growth factors in regulating bone mineralisation. Oral presentation. Gordon Research Seminar. Bones and Teeth Galveston Texas.

Goring A, Boyde A Ferrara N, Olsen BR, Hesse E, Oreffo R, Schneider P, Clarkin C (2018) Osteoblast-specific VEGF deletion reveals a paracrine role for endothelial-derived growth factors in regulating bone mineralisation. Poster presentation. Gordon Research Conference. Bones and Teeth, Galveston Texas.

Goring A, Núñez JA, Ferrara N, Olsen BR, Hesse E, Oreffo R, Schneider P, Clarkin CE (2017) Evidence for gender-specific vascular signalling in bone. Oral Poster presentation. New Investigator award. Bone Research Society Annual Meeting 29th- 1st July 2017 Bristol.

Goring A, Nunez, JA, Ferrara, Olsen BR, Hesse, E Oreffo ROC, P Schneider, Clarkin CE (2017) Evidence for resistance of endothelial cells to blockade of mature osteoblast derived VEGF. Oral presentation. European Calcified Tissue Society 14-16th May 2017, Salzburg, Austria. ECTS New Investigator Award Best Presentation.

Núñez J, Goring A , E Hesse, Schneider P Thurner PJ and Clarkin CE (2017) Simultaneous visualisation of calcified bone ultrastructure and soft tissue of the intracortical vasculature using synchrotron X-ray phase contrast tomography. Oral poster presentation. European Calcified Tissue Society 14-16th May 2017. Salzburg, Austria.

Nunez J, Goring A, Ferrara N, Olsen BR, Thurner P, Schneider P and Clarkin CE (2017) Regional changes in cortical bone porosity in mice lacking vascular endothelial growth factor revealed by synchrotron x‐ray tomography. Poster presentation. European Calcified Tissue Society 14-16th May 2017, Salzburg, Austria.

Page DJ, Dawson JI, Mani R, Clarkin CE, Evans ND (2017). VEGF-associated clay gels promotes angiogenesis in an in vitro and a murine-based model: possible treatment for chronic diabetic ulcers. Poster Presentation. 16th International Clay Conference: Clays, From The Oceans To Space. 17th-21st July 2017, Granada, Spain.

Nunez J, Thurner P, Schneider P, Clarkin CE (2016) Age-related and site specific changes in intracortical vascular network revealed by high-resolution synchrotron X-ray computed tomography MEIbioeng, Keble College, Oxford, UK. Oral presentation.

Nunez J, Thurner P, Schneider P, Clarkin CE (2016) Identification of regional diversity in blood vessel structures within murine cortical bone. Bone Research Society Annual Meeting 29th- 1st July 2016, Liverpool, UK. Oral Poster presentation. Best Poster Prize.

Marfy-Smith SJ, Emery R, Pitsillides AA, Mahajan S, Clarkin CE (2016) Early Detection of Osteogenic Changes in Normal Human Osteoblasts by Raman Spectroscopy. Bone Research Society Annual Meeting 29th- 1st July 2016, Liverpool, UK. Oral Poster presentation.

Marfy-Smith SJ, Emery R, Pitsillides AA, Mahajan S, Clarkin CE (2016) Characterising an Osteogenic Signature in Primary Cells using Raman Spectroscopy. Advanced Vibrational Spectroscopy for Biomedical Applications: Faraday Discussions. 21st March- 23rd march 2016. St Catharine's College, Cambridge, UK. Poster Presentation.

Page DJ, Dawson JI, Mani R, Oreffo ROC, Clarkin CE, Evans ND (2016) Novel growth factor delivery using clay gels for the treatment of diabetic foot ulcers. Tissue & Cell Engineering Society (TCES) Annual Conference 2016. 4th-6th July, University College London (UCL), London, UK.

Page DJ, Dawson JI, Mani R, Clarkin CE, Evans ND (2016). Novel delivery of proangiogenic VEGF using clay biomaterial: potential tissue engineering application to augment diabetic foot ulcer recovery. Skin Deep – 20 Years of Research, British Skin Foundation Research Conference. 13th October 2016. Royal College of Physicians, London, UK. Poster Presentation.

DJ Page, JI Dawson, R Mani, ROC Oreffo, Clarkin CE, ND Evans (2016) VEGF-associated clay gels promotes in vitro angiogenesis:potential tissue engineering application for chronic wounds. Tissue Engineering International and Regenenerative Medicine Society, Uppsala 1st July. Poster Presentation

DJ Page, JI Dawson, R Mani, ROC Oreffo, Clarkin CE, ND Evans (2015). Novel clay gels as regenerative microenvironments for the treatment of diabetic foot ulcers. Tissue & Cell Engineering Society (TCES) Annual Conference 2015. Southampton, Poster Presentation.

Nunez J, Thurner P, Sinclair I, Schneider P & Clarkin CE (2014). Utilising high resolution imaging to interrogate blood vessel and bone cell interactions. Medical Engineering Centres Annual Meeting and Bioengineering Imperial College, London. Poster Presentation.
Shah M, Reilly P, Emery R, Clarkin CE, Pitsillides A (2013) Human osteoblasts from distinct bone locations exhibit highly conserved differences in osteogenic and pro-angiogenic potential British Orthopaedic Research Society Annual Meeting, Oxford Poster presentation.
Spink E, Morneo I, Clarkin CE (2013) Loss Of Sensitivity To VEGF And VEGF Receptor 2 Expression Provides Evidence For Vascular Endothelial Cell Dedifferentiation Upon Direct Contact With Osteoblasts. Gordon Conference on Biomaterials and Tissue Engineering Holderness, New Hampshire USA. Poster presentation.

SJ Marfy-Smith, SA Lanham, AJ Watkins, ES Lucas, CE Clarkin ROC Oreffo, T Fleming (2013) Does Maternal Diet At The Time Of Conception Influence Fetal Bone Development? Oral presentation.ociety for Reproduction and Fertility, Cambridge.

Shah M, Reilly P, Emery R, Clarkin CE, Pitsillides A (2013) The positional origins of human osteoblasts dictate growth and differentiation potential and capacity for paracrine vascular cell cross-talk via VEGF European Calcified Tissue Society , Lisbon. Poster presentation.

Spink E, Morneo I, Clarkin CE (2013) In Vitro Tracking Of Cell Fate Reveals Potential for Endothelial Cell Dedifferentiation Upon Direct Contact With Osteoblasts. Bone Research Society Annual Meeting, Oxford. 3-5th September. Poster presentation.

Staines K.A., Mackenzie N.C.W, Prideaux M., Clarkin C.E, Zelenchuk L., Bonewald L., Rowe P.S., MacRae V.E., Farquharson C (2012). Regulation of chondrocyte matrix mineralisation by the MEPE-ASARM axis. 3rd European Workshop in Growth Plate Research, Vienna (2012) Invited oral presentation.

Staines K.A., Mackenzie N.C.W., Prideaux M., Clarkin C.E., Zelenchuk L., Bonewald L., Rowe P.S., MacRae V.E., Farquharson C (2012). The MEPE-ASARM axis regulates chondrocyte matrix mineralization. Osteoporosis and Bone Conference 2012, Manchester (2012) Abstract Published - Osteoporosis International: 23 (Suppl 5) O9 Invited oral presentation.

Staines K.A., Mackenzie N.C.W., Prideaux M., Clarkin C.E., Zelenchuk L., Bonewald L., Rowe P.S., MacRae V.E., Farquharson C (2012) Regulation of endochondral ossification by the MEPE-ASARM axis. 39th European Symposium on Calcified Tissues, Stockholm (2012) Abstract published – Bone: 50(S1); S97 Invited oral presentation.

Clarkin CE, King A, Chagastelles P, Jones PM, Wheeler-Jones CPD (2012) ALK5 inhibition reverses impairment of endothelial cell viability by endogenous islet mesenchymal cells. Mesenchymal Stem cell conference, University of Southampton. Invited oral presentation.

Clarkin CE, King A, Chagastelles P, Jones PM, Wheeler-Jones CPD (2012) Lily Diabetes Oral Poster Award Basic Science Diabetes UK Oral presentation.

Clarkin CE, King A, Chagastelles P, Jones PM, Wheeler-Jones CPD (2011) Islet endothelial cell populations can be retained during in vitro culture by inhibition of TGFβ signalling. Submitted to Gordon Research Seminar Endothelial Heterogenity in disease Rhode Island, USA. Invited Oral presentation.

Clarkin CE, King A, Chagastelles P, Jones PM, Wheeler-Jones CPD (2011) Islet endothelial cell populations can be retained during in vitro culture by inhibition of TGFβ signalling. Submitted to Gordon Research Conference, Angiogenesis Rhode Island, USA. Poster presentation.

Clarkin CE (2011) Restricting Osteoblast and Endothelial Cell Proximity in Vitro Reveals Paracrine VEGF Signaling Potential in Bone. But is the Osteoblast the Chicken or the Egg? International Bone and Mineral Society, Harold Frost Young Investigator award, Sun Valley Idaho, USA. Invited Oral Presentation.

Clarkin CE, Chagastelles P, Jones PM, Wheeler-Jones CPD (2011) Human islet mesenchymal cells interact with endothelial cells and promote loss of VEGFR2 via TGFβRI signalling. The British Microcirculation Society, London, Invited Oral presentation.

Mucha N, Clarkin CE, Rackham C King A, Wheeler-Jones Caroline Jones P (2011) A Potential Role for Eph B:Ephrin B Expression in the Regulation of Beta Cell and Islet Endothelial Cell communication. German Diabetes Association Leipzig, Germany. Oral Poster presentation.

Clarkin CE, Chagastelles P, Mahmoud M, Rackham C, King A, Helen Arthur et al (2011) Maintained endoglin expression during long term islet culture reveals a population of cells with pro-angiogenic potential. Diabetes UK Annual Professional conference, London. Poster presentation.

Module Co-ordinator

BIOL3006 Cellular and Genetic aspects of Animal Development

Lecturer

BIOL3001 Current Topics of Cell Biology
BIOL3014 Molecular Cell Biology
BIOL2003 Animal Reproduction and Development

Tutor

BIOL2022 Immunology, Infection and Inflammation

University of Southampton

Biological Sciences Business (UIST enterprise) Fellow
Member of the Equality and Diversity Committee for Biological Sciences

Professional Affiliations

Review editor. Frontiers in Bone Endocrinology.
Section editor. Cardiovascular Biology, Journal of Cell Biochemistry and Function.

Athena Swan Award
Dr Claire E Clarkin
Biological Sciences
Faculty of Environmental and Life Sciences
Life Sciences Building 85
University of Southampton
Highfield Campus
Southampton
SO17 1BJ

Room Number: 85/3045

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